Nitric oxide synthase and neuronal vulnerability in parkinson's disease
Identifieur interne : 001731 ( Main/Corpus ); précédent : 001730; suivant : 001732Nitric oxide synthase and neuronal vulnerability in parkinson's disease
Auteurs : S. Hunot ; F. Boissière ; B. Faucheux ; B. Brugg ; A. Mouatt-Prigent ; Y. Agid ; E. C. HirschSource :
- Neuroscience [ 0306-4522 ] ; 1995.
English descriptors
- KwdEn :
Abstract
Parkinson's disease is characterized by a loss of dopaminergic neurons in the mesencephalon. Although the mechanism of this neuronal loss is still unknown, oxidative stress is very likely involved in the cascade of events leading to nerve cell death. Since nitric oxide could be involved in the production of free radicals, we analysed, using immunohistochemistry and histochemistry, the production systems of nitric oxide in the mesencephalon of four patients with idiopathic Parkinson's disease and three matched control subjects. Using specific antibodies directed against the inducible isoform of nitric oxide synthase (the enzyme involved in the synthesis of nitric oxide), we found evidence to suggest that this isoform was present solely in glial cells displaying the morphological characteristics of activated macrophages. Immunohistochemical analysis performed with antibodies against the neuronal isoform of nitric oxide synthase, however, revealed perikarya and processes of neurons but no glial cell staining. The number of nitric oxide synthase-containing cells was investigated by histoenzymology, using the NADPH-diaphorase activity of nitric oxide synthase. Histochemistry revealed (i) a significant increase in NADPH-diaphorasepositive glial cell density in the dopaminergic cell groups characterized by neuronal loss in Parkinson's disease and (ii) a neuronal loss in Parkinson's disease that was two-fold greater for pigmented NADPH-diaphorase-negative neurons than for pigmented NADPH-diaphorase-positive neurons.These data suggest a potentially deleterious role of glial cells producing excessive levels of nitric oxide in Parkinson's disease, which may be neurotoxic for a subpopulation of dopaminergic neurons, especially those not expressing NADPH-diaphorase activity. However, it cannot be excluded that the presence of glial cells expressing nitric oxide synthase in the substantia nigra of patients with Parkinson's disease represents a consequence of dopaminergic neuronal loss.
Url:
DOI: 10.1016/0306-4522(95)00578-1
Links to Exploration step
ISTEX:B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7CLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Nitric oxide synthase and neuronal vulnerability in parkinson's disease</title><author><name sortKey="Hunot, S" sort="Hunot, S" uniqKey="Hunot S" first="S." last="Hunot">S. Hunot</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Boissiere, F" sort="Boissiere, F" uniqKey="Boissiere F" first="F." last="Boissière">F. Boissière</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Faucheux, B" sort="Faucheux, B" uniqKey="Faucheux B" first="B." last="Faucheux">B. Faucheux</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Brugg, B" sort="Brugg, B" uniqKey="Brugg B" first="B." last="Brugg">B. Brugg</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Mouatt Prigent, A" sort="Mouatt Prigent, A" uniqKey="Mouatt Prigent A" first="A." last="Mouatt-Prigent">A. Mouatt-Prigent</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Y. Agid</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E. C." last="Hirsch">E. C. Hirsch</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C</idno><date when="1996" year="1996">1996</date><idno type="doi">10.1016/0306-4522(95)00578-1</idno><idno type="url">https://api.istex.fr/document/B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001731</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Nitric oxide synthase and neuronal vulnerability in parkinson's disease</title><author><name sortKey="Hunot, S" sort="Hunot, S" uniqKey="Hunot S" first="S." last="Hunot">S. Hunot</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Boissiere, F" sort="Boissiere, F" uniqKey="Boissiere F" first="F." last="Boissière">F. Boissière</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Faucheux, B" sort="Faucheux, B" uniqKey="Faucheux B" first="B." last="Faucheux">B. Faucheux</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Brugg, B" sort="Brugg, B" uniqKey="Brugg B" first="B." last="Brugg">B. Brugg</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Mouatt Prigent, A" sort="Mouatt Prigent, A" uniqKey="Mouatt Prigent A" first="A." last="Mouatt-Prigent">A. Mouatt-Prigent</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Y. Agid</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E. C." last="Hirsch">E. C. Hirsch</name><affiliation><mods:affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Neuroscience</title><title level="j" type="abbrev">NSC</title><idno type="ISSN">0306-4522</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1995">1995</date><biblScope unit="volume">72</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="355">355</biblScope><biblScope unit="page" to="363">363</biblScope></imprint><idno type="ISSN">0306-4522</idno></series><idno type="istex">B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C</idno><idno type="DOI">10.1016/0306-4522(95)00578-1</idno><idno type="PII">0306-4522(95)00578-1</idno><idno type="ArticleID">95005781</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0306-4522</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>A8</term><term>IFNγ</term><term>ILI-β</term><term>NADPH</term><term>NADPH-diaphorase</term><term>NGS</term><term>NO</term><term>NOS</term><term>O2−</term><term>ONOO−</term><term>PBS</term><term>PD</term><term>SN</term><term>SNpc</term><term>TBS</term><term>TNF-α</term><term>VTA</term><term>dopamine</term><term>eNOS</term><term>human</term><term>iNOS</term><term>mesencephalon</term><term>nNOS</term><term>neurodegeneration</term><term>nitric oxide</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease is characterized by a loss of dopaminergic neurons in the mesencephalon. Although the mechanism of this neuronal loss is still unknown, oxidative stress is very likely involved in the cascade of events leading to nerve cell death. Since nitric oxide could be involved in the production of free radicals, we analysed, using immunohistochemistry and histochemistry, the production systems of nitric oxide in the mesencephalon of four patients with idiopathic Parkinson's disease and three matched control subjects. Using specific antibodies directed against the inducible isoform of nitric oxide synthase (the enzyme involved in the synthesis of nitric oxide), we found evidence to suggest that this isoform was present solely in glial cells displaying the morphological characteristics of activated macrophages. Immunohistochemical analysis performed with antibodies against the neuronal isoform of nitric oxide synthase, however, revealed perikarya and processes of neurons but no glial cell staining. The number of nitric oxide synthase-containing cells was investigated by histoenzymology, using the NADPH-diaphorase activity of nitric oxide synthase. Histochemistry revealed (i) a significant increase in NADPH-diaphorasepositive glial cell density in the dopaminergic cell groups characterized by neuronal loss in Parkinson's disease and (ii) a neuronal loss in Parkinson's disease that was two-fold greater for pigmented NADPH-diaphorase-negative neurons than for pigmented NADPH-diaphorase-positive neurons.These data suggest a potentially deleterious role of glial cells producing excessive levels of nitric oxide in Parkinson's disease, which may be neurotoxic for a subpopulation of dopaminergic neurons, especially those not expressing NADPH-diaphorase activity. However, it cannot be excluded that the presence of glial cells expressing nitric oxide synthase in the substantia nigra of patients with Parkinson's disease represents a consequence of dopaminergic neuronal loss.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>S. Hunot</name><affiliations><json:string>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</json:string></affiliations></json:item><json:item><name>F. Boissière</name><affiliations><json:string>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</json:string></affiliations></json:item><json:item><name>B. Faucheux</name><affiliations><json:string>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</json:string></affiliations></json:item><json:item><name>B. Brugg</name><affiliations><json:string>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</json:string></affiliations></json:item><json:item><name>A. Mouatt-Prigent</name><affiliations><json:string>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</json:string></affiliations></json:item><json:item><name>Y. Agid</name><affiliations><json:string>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</json:string></affiliations></json:item><json:item><name>E.C. Hirsch</name><affiliations><json:string>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>dopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>human</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NADPH-diaphorase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neurodegeneration</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>nitric oxide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>mesencephalon</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>A8 : catecholaminergic cell group A8</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>eNOS : endothelial nitric oxide synthase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>IFNγ : interferongamma</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ILI-β : interleukin 1-beta</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>iNOS : inducible nitric oxide synthase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NADPH : nicotinamide adenine dinucleotide phosphate</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NGS : normal goat serum</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>nNOS : neuronal nitric oxide synthase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NO : nitric oxide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>NOS : nitric oxide synthase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>O2− : superoxide radical</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ONOO− : peroxynitrite</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PBS : phosphate-buffered saline</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PD : Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SN : substantia nigra</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>SNpc : substantia nigra pars compacta</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TBS : Tris-buffered saline</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TNF-α : tumor necrosis factor-alpha</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>VTA : ventral tegmental area</value></json:item></subject><articleId><json:string>95005781</json:string></articleId><language><json:string>eng</json:string></language><abstract>Parkinson's disease is characterized by a loss of dopaminergic neurons in the mesencephalon. Although the mechanism of this neuronal loss is still unknown, oxidative stress is very likely involved in the cascade of events leading to nerve cell death. Since nitric oxide could be involved in the production of free radicals, we analysed, using immunohistochemistry and histochemistry, the production systems of nitric oxide in the mesencephalon of four patients with idiopathic Parkinson's disease and three matched control subjects. Using specific antibodies directed against the inducible isoform of nitric oxide synthase (the enzyme involved in the synthesis of nitric oxide), we found evidence to suggest that this isoform was present solely in glial cells displaying the morphological characteristics of activated macrophages. Immunohistochemical analysis performed with antibodies against the neuronal isoform of nitric oxide synthase, however, revealed perikarya and processes of neurons but no glial cell staining. The number of nitric oxide synthase-containing cells was investigated by histoenzymology, using the NADPH-diaphorase activity of nitric oxide synthase. Histochemistry revealed (i) a significant increase in NADPH-diaphorasepositive glial cell density in the dopaminergic cell groups characterized by neuronal loss in Parkinson's disease and (ii) a neuronal loss in Parkinson's disease that was two-fold greater for pigmented NADPH-diaphorase-negative neurons than for pigmented NADPH-diaphorase-positive neurons.These data suggest a potentially deleterious role of glial cells producing excessive levels of nitric oxide in Parkinson's disease, which may be neurotoxic for a subpopulation of dopaminergic neurons, especially those not expressing NADPH-diaphorase activity. However, it cannot be excluded that the presence of glial cells expressing nitric oxide synthase in the substantia nigra of patients with Parkinson's disease represents a consequence of dopaminergic neuronal loss.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>533 x 771 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>25</keywordCount><abstractCharCount>2006</abstractCharCount><pdfWordCount>6791</pdfWordCount><pdfCharCount>35293</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>273</abstractWordCount></qualityIndicators><title>Nitric oxide synthase and neuronal vulnerability in parkinson's disease</title><pii><json:string>0306-4522(95)00578-1</json:string></pii><genre><json:string>research-article</json:string></genre><serie><volume>Vol. 60</volume><editor><json:item><name>H. Narabayashi</name></json:item><json:item><name>T. Nagatsu</name></json:item><json:item><name>N. Yanagisawa</name></json:item><json:item><name>Y. Mizuno</name></json:item></editor><pages><last>164</last><first>148</first></pages><genre></genre><language><json:string>unknown</json:string></language><title>Advances in Neurology</title></serie><host><volume>72</volume><pii><json:string>S0306-4522(00)X0007-3</json:string></pii><pages><last>363</last><first>355</first></pages><issn><json:string>0306-4522</json:string></issn><issue>2</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><title>Neuroscience</title><publicationDate>1996</publicationDate></host><categories><wos><json:string>NEUROSCIENCES</json:string></wos></categories><publicationDate>1995</publicationDate><copyrightDate>1996</copyrightDate><doi><json:string>10.1016/0306-4522(95)00578-1</json:string></doi><id>B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C/fulltext/pdf</uri></json:item><json:item><original>true</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C/fulltext/txt</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Nitric oxide synthase and neuronal vulnerability in parkinson's disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>1996</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Nitric oxide synthase and neuronal vulnerability in parkinson's disease</title><author><persName><forename type="first">S.</forename><surname>Hunot</surname></persName><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation></author><author><persName><forename type="first">F.</forename><surname>Boissière</surname></persName><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation></author><author><persName><forename type="first">B.</forename><surname>Faucheux</surname></persName><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation></author><author><persName><forename type="first">B.</forename><surname>Brugg</surname></persName><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation></author><author><persName><forename type="first">A.</forename><surname>Mouatt-Prigent</surname></persName><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation></author><author><persName><forename type="first">Y.</forename><surname>Agid</surname></persName><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation></author><author><persName><forename type="first">E.C.</forename><surname>Hirsch</surname></persName><affiliation>To whom correspondence should be addressed.</affiliation><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation></author></analytic><monogr><title level="j">Neuroscience</title><title level="j" type="abbrev">NSC</title><idno type="pISSN">0306-4522</idno><idno type="PII">S0306-4522(00)X0007-3</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1995"></date><biblScope unit="volume">72</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="355">355</biblScope><biblScope unit="page" to="363">363</biblScope></imprint></monogr><idno type="istex">B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C</idno><idno type="DOI">10.1016/0306-4522(95)00578-1</idno><idno type="PII">0306-4522(95)00578-1</idno><idno type="ArticleID">95005781</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1996</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Parkinson's disease is characterized by a loss of dopaminergic neurons in the mesencephalon. Although the mechanism of this neuronal loss is still unknown, oxidative stress is very likely involved in the cascade of events leading to nerve cell death. Since nitric oxide could be involved in the production of free radicals, we analysed, using immunohistochemistry and histochemistry, the production systems of nitric oxide in the mesencephalon of four patients with idiopathic Parkinson's disease and three matched control subjects. Using specific antibodies directed against the inducible isoform of nitric oxide synthase (the enzyme involved in the synthesis of nitric oxide), we found evidence to suggest that this isoform was present solely in glial cells displaying the morphological characteristics of activated macrophages. Immunohistochemical analysis performed with antibodies against the neuronal isoform of nitric oxide synthase, however, revealed perikarya and processes of neurons but no glial cell staining. The number of nitric oxide synthase-containing cells was investigated by histoenzymology, using the NADPH-diaphorase activity of nitric oxide synthase. Histochemistry revealed (i) a significant increase in NADPH-diaphorasepositive glial cell density in the dopaminergic cell groups characterized by neuronal loss in Parkinson's disease and (ii) a neuronal loss in Parkinson's disease that was two-fold greater for pigmented NADPH-diaphorase-negative neurons than for pigmented NADPH-diaphorase-positive neurons.These data suggest a potentially deleterious role of glial cells producing excessive levels of nitric oxide in Parkinson's disease, which may be neurotoxic for a subpopulation of dopaminergic neurons, especially those not expressing NADPH-diaphorase activity. However, it cannot be excluded that the presence of glial cells expressing nitric oxide synthase in the substantia nigra of patients with Parkinson's disease represents a consequence of dopaminergic neuronal loss.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>dopamine</term></item><item><term>human</term></item><item><term>NADPH-diaphorase</term></item><item><term>neurodegeneration</term></item><item><term>nitric oxide</term></item><item><term>mesencephalon</term></item></list></keywords></textClass><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>A8</term><term>catecholaminergic cell group A8</term></item><item><term>eNOS</term><term>endothelial nitric oxide synthase</term></item><item><term>IFNγ</term><term>interferongamma</term></item><item><term>ILI-β</term><term>interleukin 1-beta</term></item><item><term>iNOS</term><term>inducible nitric oxide synthase</term></item><item><term>NADPH</term><term>nicotinamide adenine dinucleotide phosphate</term></item><item><term>NGS</term><term>normal goat serum</term></item><item><term>nNOS</term><term>neuronal nitric oxide synthase</term></item><item><term>NO</term><term>nitric oxide</term></item><item><term>NOS</term><term>nitric oxide synthase</term></item><item><term>O2−</term><term>superoxide radical</term></item><item><term>ONOO−</term><term>peroxynitrite</term></item><item><term>PBS</term><term>phosphate-buffered saline</term></item><item><term>PD</term><term>Parkinson's disease</term></item><item><term>SN</term><term>substantia nigra</term></item><item><term>SNpc</term><term>substantia nigra pars compacta</term></item><item><term>TBS</term><term>Tris-buffered saline</term></item><item><term>TNF-α</term><term>tumor necrosis factor-alpha</term></item><item><term>VTA</term><term>ventral tegmental area</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1995-12-04">Registration</change><change when="1995">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier doc found" wicri:toSee="Elsevier, no converted or simple article"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 5.0.1//EN//XML" URI="art501.dtd" name="istex:docType"></istex:docType><istex:document><article version="5.0" xml:lang="en" docsubtype="fla"><item-info><jid>NSC</jid><aid>95005781</aid><ce:pii>0306-4522(95)00578-1</ce:pii><ce:doi>10.1016/0306-4522(95)00578-1</ce:doi><ce:copyright type="unknown" year="1996">IBRO</ce:copyright></item-info><head><ce:title>Nitric oxide synthase and neuronal vulnerability in parkinson's disease</ce:title><ce:author-group><ce:author><ce:given-name>S.</ce:given-name><ce:surname>Hunot</ce:surname></ce:author><ce:author><ce:given-name>F.</ce:given-name><ce:surname>Boissière</ce:surname></ce:author><ce:author><ce:given-name>B.</ce:given-name><ce:surname>Faucheux</ce:surname></ce:author><ce:author><ce:given-name>B.</ce:given-name><ce:surname>Brugg</ce:surname></ce:author><ce:author><ce:given-name>A.</ce:given-name><ce:surname>Mouatt-Prigent</ce:surname></ce:author><ce:author><ce:given-name>Y.</ce:given-name><ce:surname>Agid</ce:surname></ce:author><ce:author><ce:given-name>E.C.</ce:given-name><ce:surname>Hirsch</ce:surname><ce:cross-ref refid="cor1"><ce:sup>*</ce:sup></ce:cross-ref></ce:author><ce:affiliation><ce:textfn>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</ce:textfn></ce:affiliation><ce:correspondence id="cor1"><ce:label>*</ce:label><ce:text>To whom correspondence should be addressed.</ce:text></ce:correspondence></ce:author-group><ce:date-accepted day="4" month="12" year="1995"></ce:date-accepted><ce:abstract id="ab1" class="author" xml:lang="en"><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Parkinson's disease is characterized by a loss of dopaminergic neurons in the mesencephalon. Although the mechanism of this neuronal loss is still unknown, oxidative stress is very likely involved in the cascade of events leading to nerve cell death. Since nitric oxide could be involved in the production of free radicals, we analysed, using immunohistochemistry and histochemistry, the production systems of nitric oxide in the mesencephalon of four patients with idiopathic Parkinson's disease and three matched control subjects. Using specific antibodies directed against the inducible isoform of nitric oxide synthase (the enzyme involved in the synthesis of nitric oxide), we found evidence to suggest that this isoform was present solely in glial cells displaying the morphological characteristics of activated macrophages. Immunohistochemical analysis performed with antibodies against the neuronal isoform of nitric oxide synthase, however, revealed perikarya and processes of neurons but no glial cell staining. The number of nitric oxide synthase-containing cells was investigated by histoenzymology, using the NADPH-diaphorase activity of nitric oxide synthase. Histochemistry revealed (i) a significant increase in NADPH-diaphorasepositive glial cell density in the dopaminergic cell groups characterized by neuronal loss in Parkinson's disease and (ii) a neuronal loss in Parkinson's disease that was two-fold greater for pigmented NADPH-diaphorase-negative neurons than for pigmented NADPH-diaphorase-positive neurons.</ce:simple-para><ce:simple-para>These data suggest a potentially deleterious role of glial cells producing excessive levels of nitric oxide in Parkinson's disease, which may be neurotoxic for a subpopulation of dopaminergic neurons, especially those not expressing NADPH-diaphorase activity. However, it cannot be excluded that the presence of glial cells expressing nitric oxide synthase in the substantia nigra of patients with Parkinson's disease represents a consequence of dopaminergic neuronal loss.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>dopamine</ce:text></ce:keyword><ce:keyword><ce:text>human</ce:text></ce:keyword><ce:keyword><ce:text>NADPH-diaphorase</ce:text></ce:keyword><ce:keyword><ce:text>neurodegeneration</ce:text></ce:keyword><ce:keyword><ce:text>nitric oxide</ce:text></ce:keyword><ce:keyword><ce:text>mesencephalon</ce:text></ce:keyword></ce:keywords><ce:keywords class="abr"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>A8</ce:text><ce:keyword><ce:text>catecholaminergic cell group A8</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>eNOS</ce:text><ce:keyword><ce:text>endothelial nitric oxide synthase</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>IFNγ</ce:text><ce:keyword><ce:text>interferongamma</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>ILI-β</ce:text><ce:keyword><ce:text>interleukin 1-beta</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>iNOS</ce:text><ce:keyword><ce:text>inducible nitric oxide synthase</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>NADPH</ce:text><ce:keyword><ce:text>nicotinamide adenine dinucleotide phosphate</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>NGS</ce:text><ce:keyword><ce:text>normal goat serum</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>nNOS</ce:text><ce:keyword><ce:text>neuronal nitric oxide synthase</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>NO</ce:text><ce:keyword><ce:text>nitric oxide</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>NOS</ce:text><ce:keyword><ce:text>nitric oxide synthase</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>O<ce:inf>2</ce:inf><ce:sup>−</ce:sup></ce:text><ce:keyword><ce:text>superoxide radical</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>ONOO<ce:sup>−</ce:sup></ce:text><ce:keyword><ce:text>peroxynitrite</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PBS</ce:text><ce:keyword><ce:text>phosphate-buffered saline</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PD</ce:text><ce:keyword><ce:text>Parkinson's disease</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>SN</ce:text><ce:keyword><ce:text>substantia nigra</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>SNpc</ce:text><ce:keyword><ce:text>substantia nigra pars compacta</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>TBS</ce:text><ce:keyword><ce:text>Tris-buffered saline</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>TNF-α</ce:text><ce:keyword><ce:text>tumor necrosis factor-alpha</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>VTA</ce:text><ce:keyword><ce:text>ventral tegmental area</ce:text></ce:keyword></ce:keyword></ce:keywords></head><tail><ce:bibliography><ce:section-title>Reference</ce:section-title><ce:bibliography-sec><ce:bib-reference id="bib1"><ce:label>1.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Agid</ce:surname><ce:given-name>Y.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Parkinson's disease: pathophysiology</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Lancet</sb:maintitle></sb:title><sb:volume-nr>337</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>1321</sb:first-page><sb:last-page>1324</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib2"><ce:label>2.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Agid</ce:surname><ce:given-name>Y.</ce:given-name></sb:author><sb:author><ce:surname>Ruberg</ce:surname><ce:given-name>M.</ce:given-name></sb:author><sb:author><ce:surname>Javoy-Agid</ce:surname><ce:given-name>F.</ce:given-name></sb:author><sb:author><ce:surname>Hirsch</ce:surname><ce:given-name>E.</ce:given-name></sb:author><sb:author><ce:surname>Raisman-Vozari</ce:surname><ce:given-name>R.</ce:given-name></sb:author><sb:author><ce:surname>Vyas</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Faucheux</ce:surname><ce:given-name>B.</ce:given-name></sb:author><sb:author><ce:surname>Michel</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Kastner</ce:surname><ce:given-name>A.</ce:given-name></sb:author><sb:author><ce:surname>Blanchard</ce:surname><ce:given-name>V.</ce:given-name></sb:author><sb:author><ce:surname>Damier</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Villares</ce:surname><ce:given-name>J.</ce:given-name></sb:author><sb:author><ce:surname>Zhang</ce:surname><ce:given-name>P.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Are dopaminergic neurons selectively vulnerable to Parkinson's disease?</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:editors><sb:editor><ce:surname>Narabayashi</ce:surname><ce:given-name>H.</ce:given-name></sb:editor><sb:editor><ce:surname>Nagatsu</ce:surname><ce:given-name>T.</ce:given-name></sb:editor><sb:editor><ce:surname>Yanagisawa</ce:surname><ce:given-name>N.</ce:given-name></sb:editor><sb:editor><ce:surname>Mizuno</ce:surname><ce:given-name>Y.</ce:given-name></sb:editor></sb:editors><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Advances in Neurology</sb:maintitle></sb:title><sb:volume-nr>Vol. 60</sb:volume-nr></sb:series></sb:book-series><sb:date>1993</sb:date><sb:publisher><sb:name>Raven Press</sb:name><sb:location>New York</sb:location></sb:publisher></sb:edited-book><sb:pages><sb:first-page>148</sb:first-page><sb:last-page>164</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib3"><ce:label>3.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Banati</ce:surname><ce:given-name>R.B.</ce:given-name></sb:author><sb:author><ce:surname>Gehrmann</ce:surname><ce:given-name>J.</ce:given-name></sb:author><sb:author><ce:surname>Schubert</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Kreutzberg</ce:surname><ce:given-name>G.W.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Cytotoxicity of microglia</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Glia</sb:maintitle></sb:title><sb:volume-nr>7</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>111</sb:first-page><sb:last-page>118</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib4"><ce:label>4.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Beckman</ce:surname><ce:given-name>J.S.</ce:given-name></sb:author><sb:author><ce:surname>Beckman</ce:surname><ce:given-name>T.W.</ce:given-name></sb:author><sb:author><ce:surname>Chen</ce:surname><ce:given-name>J.</ce:given-name></sb:author><sb:author><ce:surname>Marshall</ce:surname><ce:given-name>P.A.</ce:given-name></sb:author><sb:author><ce:surname>Freeman</ce:surname><ce:given-name>B.A.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Proc. natn. Acad. Sci. U.S.A.</sb:maintitle></sb:title><sb:volume-nr>87</sb:volume-nr></sb:series></sb:book-series><sb:date>1990</sb:date></sb:edited-book><sb:pages><sb:first-page>1620</sb:first-page><sb:last-page>1624</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib5"><ce:label>5.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Bö</ce:surname><ce:given-name>L.</ce:given-name></sb:author><sb:author><ce:surname>Dawson</ce:surname><ce:given-name>T.M.</ce:given-name></sb:author><sb:author><ce:surname>Wesselingh</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Mörk</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Choi</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Kong</ce:surname><ce:given-name>P.A.</ce:given-name></sb:author><sb:author><ce:surname>Hanley</ce:surname><ce:given-name>D.</ce:given-name></sb:author><sb:author><ce:surname>Trapp</ce:surname><ce:given-name>B.D.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Ann. Neurol.</sb:maintitle></sb:title><sb:volume-nr>36</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>778</sb:first-page><sb:last-page>786</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib6"><ce:label>6.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Boka</ce:surname><ce:given-name>G.</ce:given-name></sb:author><sb:author><ce:surname>Anglade</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Wallach</ce:surname><ce:given-name>D.</ce:given-name></sb:author><sb:author><ce:surname>Javoy-Agid</ce:surname><ce:given-name>F.</ce:given-name></sb:author><sb:author><ce:surname>Agid</ce:surname><ce:given-name>Y.</ce:given-name></sb:author><sb:author><ce:surname>Hirsch</ce:surname><ce:given-name>E.C.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neurosci. Lett.</sb:maintitle></sb:title><sb:volume-nr>172</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>151</sb:first-page><sb:last-page>154</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib7"><ce:label>7.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Bolanoˇs</ce:surname><ce:given-name>J.P.</ce:given-name></sb:author><sb:author><ce:surname>Peuchen</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Heales</ce:surname><ce:given-name>S.J.R.</ce:given-name></sb:author><sb:author><ce:surname>Land</ce:surname><ce:given-name>J.M.</ce:given-name></sb:author><sb:author><ce:surname>Clark</ce:surname><ce:given-name>J.B.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Nitric oxide-mediated inhibition of the mitochondrial respiratory chain in cultured astrocytes</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>63</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>910</sb:first-page><sb:last-page>916</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib8"><ce:label>8.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Bonfoco</ce:surname><ce:given-name>E.</ce:given-name></sb:author><sb:author><ce:surname>Kraine</ce:surname><ce:given-name>D.</ce:given-name></sb:author><sb:author><ce:surname>Nicotera</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Lipton</ce:surname><ce:given-name>A.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>NMDA or nitric oxide (NO)/superoxide (O<ce:inf>2</ce:inf><ce:sup>−</ce:sup>)induces apoptosis in rat cortical cultures</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Soc. Neurosci. Abstr.</sb:maintitle></sb:title><sb:volume-nr>20</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>278.8</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib9"><ce:label>9.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Bredt</ce:surname><ce:given-name>D.S.</ce:given-name></sb:author><sb:author><ce:surname>Glatt</ce:surname><ce:given-name>C.E.</ce:given-name></sb:author><sb:author><ce:surname>Hwang</ce:surname><ce:given-name>P.M.</ce:given-name></sb:author><sb:author><ce:surname>Fotuhi</ce:surname><ce:given-name>M.</ce:given-name></sb:author><sb:author><ce:surname>Dawson</ce:surname><ce:given-name>T.M.</ce:given-name></sb:author><sb:author><ce:surname>Snyder</ce:surname><ce:given-name>S.H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neuron</sb:maintitle></sb:title><sb:volume-nr>7</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>615</sb:first-page><sb:last-page>624</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib10"><ce:label>10.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Bredt</ce:surname><ce:given-name>D.S.</ce:given-name></sb:author><sb:author><ce:surname>Hwang</ce:surname><ce:given-name>P.M.</ce:given-name></sb:author><sb:author><ce:surname>Glatt</ce:surname><ce:given-name>C.E.</ce:given-name></sb:author><sb:author><ce:surname>Lowenstein</ce:surname><ce:given-name>C.</ce:given-name></sb:author><sb:author><ce:surname>Reed</ce:surname><ce:given-name>R.R.</ce:given-name></sb:author><sb:author><ce:surname>Snyder</ce:surname><ce:given-name>S.H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Nature</sb:maintitle></sb:title><sb:volume-nr>351</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>714</sb:first-page><sb:last-page>718</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib11"><ce:label>11.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Bredt</ce:surname><ce:given-name>D.S.</ce:given-name></sb:author><sb:author><ce:surname>Hwang</ce:surname><ce:given-name>P.M.</ce:given-name></sb:author><sb:author><ce:surname>Snyder</ce:surname><ce:given-name>S.H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Localization of nitric oxide synthase indicating a neuronal role for nitric oxide</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Nature</sb:maintitle></sb:title><sb:volume-nr>347</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>768</sb:first-page><sb:last-page>770</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib12"><ce:label>12.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Bredt</ce:surname><ce:given-name>D.S.</ce:given-name></sb:author><sb:author><ce:surname>Snyder</ce:surname><ce:given-name>S.H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Isolation of nitric oxide synthase: a calmodulin-requiring enzyme</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Proc. natn. Acad. Sci. U.S.A.</sb:maintitle></sb:title><sb:volume-nr>87</sb:volume-nr></sb:series></sb:book-series><sb:date>1990</sb:date></sb:edited-book><sb:pages><sb:first-page>682</sb:first-page><sb:last-page>685</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib13"><ce:label>13.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Chao</ce:surname><ce:given-name>C.C.</ce:given-name></sb:author><sb:author><ce:surname>Hu</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Molitor</ce:surname><ce:given-name>T.W.</ce:given-name></sb:author><sb:author><ce:surname>Shaskan</ce:surname><ce:given-name>E.G.</ce:given-name></sb:author><sb:author><ce:surname>Peterson</ce:surname><ce:given-name>P.K.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Activated microglia mediate neuronal cell injury via a nitric oxide mechanism</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immun.</sb:maintitle></sb:title><sb:volume-nr>149</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>2736</sb:first-page><sb:last-page>2741</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib14"><ce:label>14.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Dawson</ce:surname><ce:given-name>T.M.</ce:given-name></sb:author><sb:author><ce:surname>Dawson</ce:surname><ce:given-name>V.L.</ce:given-name></sb:author><sb:author><ce:surname>Snyder</ce:surname><ce:given-name>S.H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>A novel neuronal messenger molecule in brains: the free radical, nitric oxide</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Ann. Neurol.</sb:maintitle></sb:title><sb:volume-nr>32</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>297</sb:first-page><sb:last-page>311</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib15"><ce:label>15.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Dawson</ce:surname><ce:given-name>V.L.</ce:given-name></sb:author><sb:author><ce:surname>Brahmbhatt</ce:surname><ce:given-name>H.P.</ce:given-name></sb:author><sb:author><ce:surname>Mong</ce:surname><ce:given-name>J.A.</ce:given-name></sb:author><sb:author><ce:surname>Dawson</ce:surname><ce:given-name>T.M.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Expression of inducible nitric oxide synthase causes delayed neurotoxicity in primary mixed neuronal-glial cortical cultures</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neuropharmacology</sb:maintitle></sb:title><sb:volume-nr>33</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>1425</sb:first-page><sb:last-page>1430</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib16"><ce:label>16.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Dawson</ce:surname><ce:given-name>V.L.</ce:given-name></sb:author><sb:author><ce:surname>Dawson</ce:surname><ce:given-name>T.M.</ce:given-name></sb:author><sb:author><ce:surname>London</ce:surname><ce:given-name>E.D.</ce:given-name></sb:author><sb:author><ce:surname>Bredt</ce:surname><ce:given-name>D.S.</ce:given-name></sb:author><sb:author><ce:surname>Snyder</ce:surname><ce:given-name>S.H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Proc. natn. Acad. Sci. U.S.A.</sb:maintitle></sb:title><sb:volume-nr>88</sb:volume-nr></sb:series></sb:book-series><sb:date>1991</sb:date></sb:edited-book><sb:pages><sb:first-page>6368</sb:first-page><sb:last-page>6371</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib17"><ce:label>17.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Demerlé-Pallardy</ce:surname><ce:given-name>C.</ce:given-name></sb:author><sb:author><ce:surname>Lonchampt</ce:surname><ce:given-name>M.-O.</ce:given-name></sb:author><sb:author><ce:surname>Chabrier</ce:surname><ce:given-name>P.-E.</ce:given-name></sb:author><sb:author><ce:surname>Braquet</ce:surname><ce:given-name>P.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Nitric oxide synthase induction in glial cells: effect on neuronal survival</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Life Sci.</sb:maintitle></sb:title><sb:volume-nr>52</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>1883</sb:first-page><sb:last-page>1890</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib18"><ce:label>18.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Dexter</ce:surname><ce:given-name>D.T.</ce:given-name></sb:author><sb:author><ce:surname>Carayaon</ce:surname><ce:given-name>A.</ce:given-name></sb:author><sb:author><ce:surname>Vidailhet</ce:surname><ce:given-name>M.</ce:given-name></sb:author><sb:author><ce:surname>Ruberg</ce:surname><ce:given-name>M.</ce:given-name></sb:author><sb:author><ce:surname>Agid</ce:surname><ce:given-name>F.</ce:given-name></sb:author><sb:author><ce:surname>Agid</ce:surname><ce:given-name>Y.</ce:given-name></sb:author><sb:author><ce:surname>Lees</ce:surname><ce:given-name>A.J.</ce:given-name></sb:author><sb:author><ce:surname>Wells</ce:surname><ce:given-name>F.R.</ce:given-name></sb:author><sb:author><ce:surname>Jenner</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Marsden</ce:surname><ce:given-name>C.D.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Decreased ferritin levels in brain in Parkinson's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>55</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>16</sb:first-page><sb:last-page>20</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib19"><ce:label>19.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Dexter</ce:surname><ce:given-name>D.T.</ce:given-name></sb:author><sb:author><ce:surname>Carter</ce:surname><ce:given-name>C.J.</ce:given-name></sb:author><sb:author><ce:surname>Wells</ce:surname><ce:given-name>F.R.</ce:given-name></sb:author><sb:author><ce:surname>Javoy-Agid</ce:surname><ce:given-name>F.</ce:given-name></sb:author><sb:author><ce:surname>Agid</ce:surname><ce:given-name>Y.</ce:given-name></sb:author><sb:author><ce:surname>Lees</ce:surname><ce:given-name>A.</ce:given-name></sb:author><sb:author><ce:surname>Jenner</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Marsden</ce:surname><ce:given-name>C.D.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>52</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>381</sb:first-page><sb:last-page>389</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib20"><ce:label>20.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Dexter</ce:surname><ce:given-name>D.T.</ce:given-name></sb:author><sb:author><ce:surname>Wells</ce:surname><ce:given-name>F.R.</ce:given-name></sb:author><sb:author><ce:surname>Lees</ce:surname><ce:given-name>A.J.</ce:given-name></sb:author><sb:author><ce:surname>Agid</ce:surname><ce:given-name>F.</ce:given-name></sb:author><sb:author><ce:surname>Agid</ce:surname><ce:given-name>Y.</ce:given-name></sb:author><sb:author><ce:surname>Jenner</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Marsden</ce:surname><ce:given-name>C.D.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>52</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>1830</sb:first-page><sb:last-page>1836</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib21"><ce:label>21.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Earle</ce:surname><ce:given-name>K.M.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Studies on Parkinson's disease including X-ray fluorescent spectroscopy of formalin fixed brain tissue</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neuropath. exp. Neural.</sb:maintitle></sb:title><sb:volume-nr>27</sb:volume-nr></sb:series><sb:date>1968</sb:date></sb:issue><sb:pages><sb:first-page>1</sb:first-page><sb:last-page>14</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib22"><ce:label>22.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Egberongbe</ce:surname><ce:given-name>Y.I.</ce:given-name></sb:author><sb:author><ce:surname>Gentleman</ce:surname><ce:given-name>S.M.</ce:given-name></sb:author><sb:author><ce:surname>Falkai</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Bogerts</ce:surname><ce:given-name>B.</ce:given-name></sb:author><sb:author><ce:surname>Polak</ce:surname><ce:given-name>J.M.</ce:given-name></sb:author><sb:author><ce:surname>Roberts</ce:surname><ce:given-name>G.W.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>The distribution of nitric oxide synthase immunoreactivity in the human brain</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neuroscience</sb:maintitle></sb:title><sb:volume-nr>59</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>561</sb:first-page><sb:last-page>578</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib23"><ce:label>23.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Endoh</ce:surname><ce:given-name>M.</ce:given-name></sb:author><sb:author><ce:surname>Maiese</ce:surname><ce:given-name>K.</ce:given-name></sb:author><sb:author><ce:surname>Pulsinelli</ce:surname><ce:given-name>W.A.</ce:given-name></sb:author><sb:author><ce:surname>Wagner</ce:surname><ce:given-name>J.A.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Reactive astrocytes express NADPH diaphorase <ce:italic>in vivo</ce:italic> after transient ischemia</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neurosci. Lett.</sb:maintitle></sb:title><sb:volume-nr>54</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>125</sb:first-page><sb:last-page>128</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib24"><ce:label>24.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Endoh</ce:surname><ce:given-name>M.</ce:given-name></sb:author><sb:author><ce:surname>Maiese</ce:surname><ce:given-name>K.</ce:given-name></sb:author><sb:author><ce:surname>Wagner</ce:surname><ce:given-name>J.A.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Reactive astrocytes express inducible nitric oxide synthase after ischemia</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Soc. Neurosci. Abstr.</sb:maintitle></sb:title><sb:volume-nr>19</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>1660</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib25"><ce:label>25.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Faucheux</ce:surname><ce:given-name>B.A.</ce:given-name></sb:author><sb:author><ce:surname>Nillesse</ce:surname><ce:given-name>N.</ce:given-name></sb:author><sb:author><ce:surname>Damier</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Spik</ce:surname><ce:given-name>G.</ce:given-name></sb:author><sb:author><ce:surname>Mouatt-Prigent</ce:surname><ce:given-name>A.</ce:given-name></sb:author><sb:author><ce:surname>Pierce</ce:surname><ce:given-name>A.</ce:given-name></sb:author><sb:author><ce:surname>Leveugle</ce:surname><ce:given-name>B.</ce:given-name></sb:author><sb:author><ce:surname>Kubis</ce:surname><ce:given-name>N.</ce:given-name></sb:author><sb:author><ce:surname>Hauw</ce:surname><ce:given-name>J.J.</ce:given-name></sb:author><sb:author><ce:surname>Agid</ce:surname><ce:given-name>Y.</ce:given-name></sb:author><sb:author><ce:surname>Hirsch</ce:surname><ce:given-name>E.C.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Proc. natn. Acad. Sci. U.S.A.</sb:maintitle></sb:title><sb:volume-nr>92</sb:volume-nr></sb:series></sb:book-series><sb:date>1995</sb:date></sb:edited-book><sb:pages><sb:first-page>9603</sb:first-page><sb:last-page>9607</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib26"><ce:label>26.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Ferrante</ce:surname><ce:given-name>R.J.</ce:given-name></sb:author><sb:author><ce:surname>Kowall</ce:surname><ce:given-name>N.W.</ce:given-name></sb:author><sb:author><ce:surname>Beal</ce:surname><ce:given-name>M.F.</ce:given-name></sb:author><sb:author><ce:surname>Richardson</ce:surname><ce:given-name>E.P.</ce:given-name></sb:author><sb:author><ce:surname>Bird</ce:surname><ce:given-name>E.P.</ce:given-name></sb:author><sb:author><ce:surname>Martin</ce:surname><ce:given-name>J.B.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Selective sparing of a class of striatal neurons in Huntington's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Science</sb:maintitle></sb:title><sb:volume-nr>230</sb:volume-nr></sb:series><sb:date>1985</sb:date></sb:issue><sb:pages><sb:first-page>561</sb:first-page><sb:last-page>563</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib27"><ce:label>27.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Good</ce:surname><ce:given-name>P.F.</ce:given-name></sb:author><sb:author><ce:surname>Olanow</ce:surname><ce:given-name>C.W.</ce:given-name></sb:author><sb:author><ce:surname>Perl</ce:surname><ce:given-name>D.P.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminium in Parkinson's disease: a LAMMA study</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Brain Res.</sb:maintitle></sb:title><sb:volume-nr>593</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>343</sb:first-page><sb:last-page>346</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib28"><ce:label>28.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Hirsch</ce:surname><ce:given-name>E.</ce:given-name></sb:author><sb:author><ce:surname>Graybiel</ce:surname><ce:given-name>A.M.</ce:given-name></sb:author><sb:author><ce:surname>Agid</ce:surname><ce:given-name>Y.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Nature</sb:maintitle></sb:title><sb:volume-nr>334</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>345</sb:first-page><sb:last-page>348</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib29"><ce:label>29.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Hirsch</ce:surname><ce:given-name>E.C.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Does oxidative stress participate in nerve cell death in Parkinson's disease?</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. Neurol.</sb:maintitle></sb:title><sb:volume-nr>33</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>52</sb:first-page><sb:last-page>59</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib30"><ce:label>30.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Hirsch</ce:surname><ce:given-name>E.C.</ce:given-name></sb:author><sb:author><ce:surname>Brandel</ce:surname><ce:given-name>J.P.</ce:given-name></sb:author><sb:author><ce:surname>Galle</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Javoy-Agid</ce:surname><ce:given-name>F.</ce:given-name></sb:author><sb:author><ce:surname>Agid</ce:surname><ce:given-name>Y.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Iron and aluminium increase in the substantia nigra of patients with Parkinson's disease. An X-ray microanalysis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>56</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>446</sb:first-page><sb:last-page>451</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib31"><ce:label>31.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Hope</ce:surname><ce:given-name>B.T.</ce:given-name></sb:author><sb:author><ce:surname>Michael</ce:surname><ce:given-name>G.J.</ce:given-name></sb:author><sb:author><ce:surname>Knigge</ce:surname><ce:given-name>K.M.</ce:given-name></sb:author><sb:author><ce:surname>Vincent</ce:surname><ce:given-name>S.R.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Neuronal NADPH diaphorase is a nitric oxide synthase</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Proc. natn. Acad. Sci. U.S.A.</sb:maintitle></sb:title><sb:volume-nr>88</sb:volume-nr></sb:series></sb:book-series><sb:date>1991</sb:date></sb:edited-book><sb:pages><sb:first-page>2811</sb:first-page><sb:last-page>2814</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib32"><ce:label>32.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Hsu</ce:surname><ce:given-name>S.M.</ce:given-name></sb:author><sb:author><ce:surname>Raine</ce:surname><ce:given-name>L.</ce:given-name></sb:author><sb:author><ce:surname>Fanger</ce:surname><ce:given-name>H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Use of avidin-biotin-peroxidase complex (ABC) in immuno-peroxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Histochem. Cytochem.</sb:maintitle></sb:title><sb:volume-nr>29</sb:volume-nr></sb:series><sb:date>1981</sb:date></sb:issue><sb:pages><sb:first-page>577</sb:first-page><sb:last-page>580</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib33"><ce:label>33.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Jellinger</ce:surname><ce:given-name>K.</ce:given-name></sb:author><sb:author><ce:surname>Kienzl</ce:surname><ce:given-name>E.</ce:given-name></sb:author><sb:author><ce:surname>Rumpelmair</ce:surname><ce:given-name>G.</ce:given-name></sb:author><sb:author><ce:surname>Riederer</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Stachelberger</ce:surname><ce:given-name>H.</ce:given-name></sb:author><sb:author><ce:surname>Ben-Shachar</ce:surname><ce:given-name>D.</ce:given-name></sb:author><sb:author><ce:surname>Youdim</ce:surname><ce:given-name>M.B.H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Ironmelanin complex in substantia nigra of Parkinsonian brains: An X-ray microanalysis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>59</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>1168</sb:first-page><sb:last-page>1171</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib34"><ce:label>34.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Jun</ce:surname><ce:given-name>C.-D.</ce:given-name></sb:author><sb:author><ce:surname>Choi</ce:surname><ce:given-name>B.-M.</ce:given-name></sb:author><sb:author><ce:surname>H.-Ryu</ce:surname></sb:author><sb:author><ce:surname>Um</ce:surname><ce:given-name>J.-Y.</ce:given-name></sb:author><sb:author><ce:surname>Kwak</ce:surname><ce:given-name>H.-J.</ce:given-name></sb:author><sb:author><ce:surname>Lee</ce:surname><ce:given-name>B.-S.</ce:given-name></sb:author><sb:author><ce:surname>Paik</ce:surname><ce:given-name>S.-G.</ce:given-name></sb:author><sb:author><ce:surname>Kim</ce:surname><ce:given-name>H.-M.</ce:given-name></sb:author><sb:author><ce:surname>Chung</ce:surname><ce:given-name>H.-T.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Synergistic cooperation between phorbol ester and IFN-γ for induction of nitric oxide synthesis in murine peritoneal macrophages</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immun.</sb:maintitle></sb:title><sb:volume-nr>153</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>3684</sb:first-page><sb:last-page>3690</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib35"><ce:label>35.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Kopmels</ce:surname><ce:given-name>B.</ce:given-name></sb:author><sb:author><ce:surname>Wollman</ce:surname><ce:given-name>E.E.</ce:given-name></sb:author><sb:author><ce:surname>Guastavino</ce:surname><ce:given-name>J.M.</ce:given-name></sb:author><sb:author><ce:surname>Delhaye-Bouchaud</ce:surname><ce:given-name>N.</ce:given-name></sb:author><sb:author><ce:surname>Fradelizi</ce:surname><ce:given-name>D.</ce:given-name></sb:author><sb:author><ce:surname>Mariani</ce:surname><ce:given-name>J.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Interleukine-1 hyperproduction by in vitro activated peripheral macrophages from cerebellar mutant mice</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>55</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>1980</sb:first-page><sb:last-page>1985</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib36"><ce:label>36.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Kowall</ce:surname><ce:given-name>N.W.</ce:given-name></sb:author><sb:author><ce:surname>Beal</ce:surname><ce:given-name>M.F.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Cortical somatostatin, neuropeptide Y and NADPH diaphorase neurons: normal anatomy and alterations in Alzheimer's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Ann. Neurol.</sb:maintitle></sb:title><sb:volume-nr>23</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>105</sb:first-page><sb:last-page>114</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib37"><ce:label>37.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Lamas</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Marsden</ce:surname><ce:given-name>P.A.</ce:given-name></sb:author><sb:author><ce:surname>Li</ce:surname><ce:given-name>G.K.</ce:given-name></sb:author><sb:author><ce:surname>Tempst</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Michel</ce:surname><ce:given-name>T.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Proc. natn. Acad. Sci. U.S.A.</sb:maintitle></sb:title><sb:volume-nr>89</sb:volume-nr></sb:series></sb:book-series><sb:date>1992</sb:date></sb:edited-book><sb:pages><sb:first-page>6348</sb:first-page><sb:last-page>6352</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib38"><ce:label>38.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Levine</ce:surname><ce:given-name>W.</ce:given-name></sb:author><sb:author><ce:surname>Giuditta</ce:surname><ce:given-name>A.</ce:given-name></sb:author><sb:author><ce:surname>Englard</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Stecker</ce:surname><ce:given-name>H.J.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Brain diaphorases</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>6</sb:volume-nr></sb:series><sb:date>1960</sb:date></sb:issue><sb:pages><sb:first-page>28</sb:first-page><sb:last-page>36</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib39"><ce:label>39.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Mallat</ce:surname><ce:given-name>M.</ce:given-name></sb:author><sb:author><ce:surname>Chamak</ce:surname><ce:given-name>B.</ce:given-name></sb:author><sb:author><ce:surname>Théry</ce:surname><ce:given-name>C.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Les macrophages cérébraux: role dans les remaniements morphologiques et la dégénérescence des neurones</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Méecine/sciences</sb:maintitle></sb:title><sb:volume-nr>7</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>768</sb:first-page><sb:last-page>774</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib40"><ce:label>40.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Matsumoto</ce:surname><ce:given-name>T.</ce:given-name></sb:author><sb:author><ce:surname>Nakane</ce:surname><ce:given-name>M.</ce:given-name></sb:author><sb:author><ce:surname>Pollock</ce:surname><ce:given-name>J.S.</ce:given-name></sb:author><sb:author><ce:surname>Kuk</ce:surname><ce:given-name>J.E.</ce:given-name></sb:author><sb:author><ce:surname>Forstermann</ce:surname><ce:given-name>U.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>A correlation between soluble brain nitric oxide synthase and NADPH-diaphorase activity is only seen after exposure of the tissue to fixative</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neurosci. Lett.</sb:maintitle></sb:title><sb:volume-nr>155</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>61</sb:first-page><sb:last-page>64</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib41"><ce:label>41.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>McGeer</ce:surname><ce:given-name>P.L.</ce:given-name></sb:author><sb:author><ce:surname>Itagaki</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Boyes</ce:surname><ce:given-name>B.E.</ce:given-name></sb:author><sb:author><ce:surname>McGeer</ce:surname><ce:given-name>E.G.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neurology</sb:maintitle></sb:title><sb:volume-nr>38</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>1285</sb:first-page><sb:last-page>1291</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib42"><ce:label>42.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Mollace</ce:surname><ce:given-name>V.</ce:given-name></sb:author><sb:author><ce:surname>Colasanti</ce:surname><ce:given-name>M.</ce:given-name></sb:author><sb:author><ce:surname>Rodino</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Massoud</ce:surname><ce:given-name>R.</ce:given-name></sb:author><sb:author><ce:surname>Lauro</ce:surname><ce:given-name>G.M.</ce:given-name></sb:author><sb:author><ce:surname>Nistico</ce:surname><ce:given-name>G.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Cytokine-induced nitric oxide generation by cultured astrocytoma cells involves a Ca<ce:sup>++</ce:sup>-calmodulin-independent NO-synthase</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Biochem. Bophys. Res. Commun.</sb:maintitle></sb:title><sb:volume-nr>191</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>327</sb:first-page><sb:last-page>332</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib43"><ce:label>43.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Moncada</ce:surname><ce:given-name>S.</ce:given-name></sb:author><sb:author><ce:surname>Palmer</ce:surname><ce:given-name>R.M.J.</ce:given-name></sb:author><sb:author><ce:surname>Higgs</ce:surname><ce:given-name>E.A.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Nitric oxide: physiology, pathophysiology, and pharmacology</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pharmac. Rev.</sb:maintitle></sb:title><sb:volume-nr>43</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>109</sb:first-page><sb:last-page>141</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib44"><ce:label>44.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Pantopoulos</ce:surname><ce:given-name>K.</ce:given-name></sb:author><sb:author><ce:surname>Hentze</ce:surname><ce:given-name>M.W.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Nitric oxide signaling to iron-regulatory protein: direct control of ferritin mRNA translation and transferrin receptor mRNA stability in transfected fibroblasts</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Proc. natn. Acad. Sci. U.S.A.</sb:maintitle></sb:title><sb:volume-nr>92</sb:volume-nr></sb:series></sb:book-series><sb:date>1995</sb:date></sb:edited-book><sb:pages><sb:first-page>1267</sb:first-page><sb:last-page>1271</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib45"><ce:label>45.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Park</ce:surname><ce:given-name>S.K.</ce:given-name></sb:author><sb:author><ce:surname>Grzybicki</ce:surname><ce:given-name>D.</ce:given-name></sb:author><sb:author><ce:surname>Lin</ce:surname><ce:given-name>H.L.</ce:given-name></sb:author><sb:author><ce:surname>Murphy</ce:surname><ce:given-name>S.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Modulation of inducible nitric oxide synthase expression in astroglial cells</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neuropharmacology</sb:maintitle></sb:title><sb:volume-nr>33</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>1419</sb:first-page><sb:last-page>1423</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib46"><ce:label>46.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Radi</ce:surname><ce:given-name>R.</ce:given-name></sb:author><sb:author><ce:surname>Beckman</ce:surname><ce:given-name>J.S.</ce:given-name></sb:author><sb:author><ce:surname>Bush</ce:surname><ce:given-name>K.M.</ce:given-name></sb:author><sb:author><ce:surname>Freeman</ce:surname><ce:given-name>B.A.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. biol. Chem.</sb:maintitle></sb:title><sb:volume-nr>266</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>4244</sb:first-page><sb:last-page>4250</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib47"><ce:label>47.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Reif</ce:surname><ce:given-name>D.W.</ce:given-name></sb:author><sb:author><ce:surname>Simmons</ce:surname><ce:given-name>R.D.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Nitric oxide mediates iron release from ferritin</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Archs Biochem. Biophys.</sb:maintitle></sb:title><sb:volume-nr>283</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>537</sb:first-page><sb:last-page>541</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib48"><ce:label>48.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Richard Lyons</ce:surname><ce:given-name>C.</ce:given-name></sb:author><sb:author><ce:surname>Orloff</ce:surname><ce:given-name>G.J.</ce:given-name></sb:author><sb:author><ce:surname>Cunningham</ce:surname><ce:given-name>J.M.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophages cell line</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. biol. Chem.</sb:maintitle></sb:title><sb:volume-nr>267</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>6370</sb:first-page><sb:last-page>6374</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib49"><ce:label>49.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Riederer</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Sofic</ce:surname><ce:given-name>E.</ce:given-name></sb:author><sb:author><ce:surname>Rausch</ce:surname><ce:given-name>W.-D.</ce:given-name></sb:author><sb:author><ce:surname>Schmidt</ce:surname><ce:given-name>B.</ce:given-name></sb:author><sb:author><ce:surname>Reynolds</ce:surname><ce:given-name>G.P.</ce:given-name></sb:author><sb:author><ce:surname>Jellinger</ce:surname><ce:given-name>K.</ce:given-name></sb:author><sb:author><ce:surname>Youdim</ce:surname><ce:given-name>M.B.H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Transition metals, ferritin, glutathione, and ascorbic acid in Parkinsonian brains</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>52</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>515</sb:first-page><sb:last-page>520</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib50"><ce:label>50.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Schapira</ce:surname><ce:given-name>A.H.V.</ce:given-name></sb:author><sb:author><ce:surname>Cooper</ce:surname><ce:given-name>J.M.</ce:given-name></sb:author><sb:author><ce:surname>Dexter</ce:surname><ce:given-name>D.</ce:given-name></sb:author><sb:author><ce:surname>Clark</ce:surname><ce:given-name>J.B.</ce:given-name></sb:author><sb:author><ce:surname>Jenner</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Marsden</ce:surname><ce:given-name>C.D.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Mitochondrial complex I deficiency in Parkinson's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>54</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>823</sb:first-page><sb:last-page>827</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib51"><ce:label>51.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Simmons</ce:surname><ce:given-name>M.L.</ce:given-name></sb:author><sb:author><ce:surname>Murphy</ce:surname><ce:given-name>S.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Induction of nitric oxide synthase in glial cells</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Neurochem.</sb:maintitle></sb:title><sb:volume-nr>59</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>897</sb:first-page><sb:last-page>905</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib52"><ce:label>52.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Sims</ce:surname><ce:given-name>K.L.</ce:given-name></sb:author><sb:author><ce:surname>Kauffman</ce:surname><ce:given-name>F.C.</ce:given-name></sb:author><sb:author><ce:surname>Johnson</ce:surname><ce:given-name>E.C.</ce:given-name></sb:author><sb:author><ce:surname>Pickel</ce:surname><ce:given-name>V.M.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Cytochemical localization of brain nicotinamide adenine dinucleotide phosphate (oxidized)-dependent dehydrogenases. Qualitative and quantitative distributions</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Histochem. Cytochem.</sb:maintitle></sb:title><sb:volume-nr>22</sb:volume-nr></sb:series><sb:date>1974</sb:date></sb:issue><sb:pages><sb:first-page>7</sb:first-page><sb:last-page>19</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib53"><ce:label>53.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Stuehr</ce:surname><ce:given-name>D.J.</ce:given-name></sb:author><sb:author><ce:surname>Nathan</ce:surname><ce:given-name>C.F.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. exp. Med.</sb:maintitle></sb:title><sb:volume-nr>169</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>1543</sb:first-page><sb:last-page>1555</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib54"><ce:label>54.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Vigne</ce:surname><ce:given-name>P.</ce:given-name></sb:author><sb:author><ce:surname>Damais</ce:surname><ce:given-name>C.</ce:given-name></sb:author><sb:author><ce:surname>Frelin</ce:surname><ce:given-name>C.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>IL1 and TNFα induce cGMP formation in C6 astrocytoma cells via the nitridergic pathway</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Brain Res.</sb:maintitle></sb:title><sb:volume-nr>606</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>332</sb:first-page><sb:last-page>336</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib55"><ce:label>55.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Vincent</ce:surname><ce:given-name>S.R.</ce:given-name></sb:author><sb:author><ce:surname>Kimura</ce:surname><ce:given-name>H.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Histochemical mapping of nitric oxide synthase in the rat brain</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neuroscience</sb:maintitle></sb:title><sb:volume-nr>46</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>755</sb:first-page><sb:last-page>784</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib56"><ce:label>56.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Wallace</ce:surname><ce:given-name>M.N.</ce:given-name></sb:author><sb:author><ce:surname>Bisland</ce:surname><ce:given-name>S.K.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>NADPH-diaphorase activity in activated astrocytes represents inducible nitric oxide synthase</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Neuroscience</sb:maintitle></sb:title><sb:volume-nr>59</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>905</sb:first-page><sb:last-page>919</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib57"><ce:label>57.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Weibel</ce:surname><ce:given-name>E.R.</ce:given-name></sb:author></sb:authors></sb:contribution><sb:host><sb:edited-book><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Stereological Methods</sb:maintitle></sb:title><sb:volume-nr>Vol. 1</sb:volume-nr></sb:series></sb:book-series><sb:date>1979</sb:date><sb:publisher><sb:name>Academic Press</sb:name><sb:location>London</sb:location></sb:publisher></sb:edited-book><sb:pages><sb:first-page>101</sb:first-page><sb:last-page>161</sb:last-page></sb:pages></sb:host><sb:comment>Chap. 4</sb:comment></sb:reference></ce:bib-reference><ce:bib-reference id="bib58"><ce:label>58.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Wink</ce:surname><ce:given-name>D.A.</ce:given-name></sb:author><sb:author><ce:surname>Hanbauer</ce:surname><ce:given-name>I.</ce:given-name></sb:author><sb:author><ce:surname>Krishna</ce:surname><ce:given-name>M.C.</ce:given-name></sb:author><sb:author><ce:surname>DeGraff</ce:surname><ce:given-name>W.</ce:given-name></sb:author><sb:author><ce:surname>Gamson</ce:surname><ce:given-name>J.</ce:given-name></sb:author><sb:author><ce:surname>Mitchell</ce:surname><ce:given-name>J.B.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Proc. natn. Acad. Sci. U.S.A.</sb:maintitle></sb:title><sb:volume-nr>90</sb:volume-nr></sb:series></sb:book-series><sb:date>1993</sb:date></sb:edited-book><sb:pages><sb:first-page>9813</sb:first-page><sb:last-page>9817</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib59"><ce:label>59.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Xie</ce:surname><ce:given-name>Q.-W.</ce:given-name></sb:author><sb:author><ce:surname>Cho</ce:surname><ce:given-name>H.J.</ce:given-name></sb:author><sb:author><ce:surname>Calaycay</ce:surname><ce:given-name>J.</ce:given-name></sb:author><sb:author><ce:surname>Mumford</ce:surname><ce:given-name>R.A.</ce:given-name></sb:author><sb:author><ce:surname>Swiderek</ce:surname><ce:given-name>K.M.</ce:given-name></sb:author><sb:author><ce:surname>Lee</ce:surname><ce:given-name>T.D.</ce:given-name></sb:author><sb:author><ce:surname>Ding</ce:surname><ce:given-name>A.</ce:given-name></sb:author><sb:author><ce:surname>Troso</ce:surname><ce:given-name>T.</ce:given-name></sb:author><sb:author><ce:surname>Nathan</ce:surname><ce:given-name>C.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Cloning and characterization of inducible nitric oxide synthase from mouse macrophages</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Science</sb:maintitle></sb:title><sb:volume-nr>256</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>225</sb:first-page><sb:last-page>228</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib60"><ce:label>60.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Youdim</ce:surname><ce:given-name>M.B.H.</ce:given-name></sb:author><sb:author><ce:surname>Ben-Shachar</ce:surname><ce:given-name>D.</ce:given-name></sb:author><sb:author><ce:surname>Eshel</ce:surname><ce:given-name>G.</ce:given-name></sb:author><sb:author><ce:surname>Finberg</ce:surname><ce:given-name>J.P.M.</ce:given-name></sb:author><sb:author><ce:surname>Riederer</ce:surname><ce:given-name>P.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>The neurotoxicity of iron and nitric oxide. Relevance to the etiology of Parkinson's disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:editors><sb:editor><ce:surname>Narabayashi</ce:surname><ce:given-name>M.</ce:given-name></sb:editor><sb:editor><ce:surname>Nagatsu</ce:surname><ce:given-name>T.</ce:given-name></sb:editor><sb:editor><ce:surname>Yanagisame</ce:surname><ce:given-name>N.</ce:given-name></sb:editor><sb:editor><ce:surname>Mizuno</ce:surname><ce:given-name>Y.</ce:given-name></sb:editor></sb:editors><sb:edition>3rd edn</sb:edition><sb:book-series><sb:series><sb:title><sb:maintitle>Advances in Neurology</sb:maintitle></sb:title><sb:volume-nr>Vol. 60</sb:volume-nr></sb:series></sb:book-series><sb:date>1993</sb:date><sb:publisher><sb:name>Raven Press</sb:name><sb:location>New York</sb:location></sb:publisher></sb:edited-book><sb:pages><sb:first-page>259</sb:first-page><sb:last-page>266</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference></ce:bibliography-sec></ce:bibliography></tail></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Nitric oxide synthase and neuronal vulnerability in parkinson's disease</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Nitric oxide synthase and neuronal vulnerability in parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">S.</namePart><namePart type="family">Hunot</namePart><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F.</namePart><namePart type="family">Boissière</namePart><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B.</namePart><namePart type="family">Faucheux</namePart><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B.</namePart><namePart type="family">Brugg</namePart><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.</namePart><namePart type="family">Mouatt-Prigent</namePart><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Y.</namePart><namePart type="family">Agid</namePart><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E.C.</namePart><namePart type="family">Hirsch</namePart><affiliation>INSERM U289, Physiopathologie et Pathogenèse des Maladies Dégénératives du Système Nerveux, Hoˆpital de la Salpêtrière, 47 bd de l'Hoˆpital, 75013 Paris, France</affiliation><description>To whom correspondence should be addressed.</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1995</dateIssued><dateValid encoding="w3cdtf">1995-12-04</dateValid><copyrightDate encoding="w3cdtf">1996</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Parkinson's disease is characterized by a loss of dopaminergic neurons in the mesencephalon. Although the mechanism of this neuronal loss is still unknown, oxidative stress is very likely involved in the cascade of events leading to nerve cell death. Since nitric oxide could be involved in the production of free radicals, we analysed, using immunohistochemistry and histochemistry, the production systems of nitric oxide in the mesencephalon of four patients with idiopathic Parkinson's disease and three matched control subjects. Using specific antibodies directed against the inducible isoform of nitric oxide synthase (the enzyme involved in the synthesis of nitric oxide), we found evidence to suggest that this isoform was present solely in glial cells displaying the morphological characteristics of activated macrophages. Immunohistochemical analysis performed with antibodies against the neuronal isoform of nitric oxide synthase, however, revealed perikarya and processes of neurons but no glial cell staining. The number of nitric oxide synthase-containing cells was investigated by histoenzymology, using the NADPH-diaphorase activity of nitric oxide synthase. Histochemistry revealed (i) a significant increase in NADPH-diaphorasepositive glial cell density in the dopaminergic cell groups characterized by neuronal loss in Parkinson's disease and (ii) a neuronal loss in Parkinson's disease that was two-fold greater for pigmented NADPH-diaphorase-negative neurons than for pigmented NADPH-diaphorase-positive neurons.These data suggest a potentially deleterious role of glial cells producing excessive levels of nitric oxide in Parkinson's disease, which may be neurotoxic for a subpopulation of dopaminergic neurons, especially those not expressing NADPH-diaphorase activity. However, it cannot be excluded that the presence of glial cells expressing nitric oxide synthase in the substantia nigra of patients with Parkinson's disease represents a consequence of dopaminergic neuronal loss.</abstract><subject lang="en"><genre>Keywords</genre><topic>dopamine</topic><topic>human</topic><topic>NADPH-diaphorase</topic><topic>neurodegeneration</topic><topic>nitric oxide</topic><topic>mesencephalon</topic></subject><subject lang="en"><genre>Abbreviations</genre><topic>A8 : catecholaminergic cell group A8</topic><topic>eNOS : endothelial nitric oxide synthase</topic><topic>IFNγ : interferongamma</topic><topic>ILI-β : interleukin 1-beta</topic><topic>iNOS : inducible nitric oxide synthase</topic><topic>NADPH : nicotinamide adenine dinucleotide phosphate</topic><topic>NGS : normal goat serum</topic><topic>nNOS : neuronal nitric oxide synthase</topic><topic>NO : nitric oxide</topic><topic>NOS : nitric oxide synthase</topic><topic>O2− : superoxide radical</topic><topic>ONOO− : peroxynitrite</topic><topic>PBS : phosphate-buffered saline</topic><topic>PD : Parkinson's disease</topic><topic>SN : substantia nigra</topic><topic>SNpc : substantia nigra pars compacta</topic><topic>TBS : Tris-buffered saline</topic><topic>TNF-α : tumor necrosis factor-alpha</topic><topic>VTA : ventral tegmental area</topic></subject><relatedItem type="host"><titleInfo><title>Neuroscience</title></titleInfo><titleInfo type="abbreviated"><title>NSC</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">199605</dateIssued></originInfo><identifier type="ISSN">0306-4522</identifier><identifier type="PII">S0306-4522(00)X0007-3</identifier><part><detail type="volume"><number>72</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="issue pages"><start>309</start><end>592</end></extent><extent unit="pages"><start>355</start><end>363</end></extent></part></relatedItem><identifier type="istex">B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C</identifier><identifier type="DOI">10.1016/0306-4522(95)00578-1</identifier><identifier type="PII">0306-4522(95)00578-1</identifier><identifier type="ArticleID">95005781</identifier><accessCondition type="use and reproduction" contentType="">© 1996IBRO</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>IBRO, ©1996</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">NEUROSCIENCES</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001731 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 001731 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:B157D8785BAACB7BB3EC52E539A7FBA2A93B5D7C
|texte= Nitric oxide synthase and neuronal vulnerability in parkinson's disease
}}
| This area was generated with Dilib version V0.6.23. |  |