Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson's disease brain
Identifieur interne : 001A86 ( Main/Exploration ); précédent : 001A85; suivant : 001A87Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson's disease brain
Auteurs : Neelima B. Chauhan [États-Unis] ; George J. Siegel [États-Unis] ; John M. Lee [États-Unis]Source :
- Journal of Chemical Neuroanatomy [ 0891-0618 ] ; 2001.
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Abstract
The distribution of nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in substantia nigra pars compacta (SNc) of Parkinson's disease (PD) brains was investigated by immunofluorescence. Cases studied included four 69–77 year old neurologically normal male controls and four 72–79 year old male PD patients. Integrated optical densities (IODs) of immunofluorescence over individual neuromelanin-containing neurons and in areas of neuropil and the number of neurons on H & E stained adjacent sections were quantitated with the use of the BioQuant Image Analyzer. Data were statistically analyzed by ANOVA, including the unpaired two-tailed Student t-test and the Mann–Whitney test. The results showed 55.8% (P<0.0001) dropout of SNc neurons in PD brains compared to age-matched controls. Despite considerable neuronal dropout, immunofluorescent NTFs in the PD brains showed differential reductions that were consistent within the group as compared to age-matched controls: reductions were GDNF, 19.4%/neuron (P<0.0001), 20.2%/neuropil (P<0.0001); CNTF, 11.1%/neuron (P<0.0001), 9.4%/neuropil (P<0.0001); BDNF, 8.6%/neuron (P<0.0001), 2.5%/neuropil. NGF, NT-3 and NT-4 showed no significant differences within surviving neurons or neuropil. Since the depletion of GDNF both within surviving neurons and neuropil was twice as great as that of CNTF and BDNF and since the other NTFs showed no changes, GDNF, of the tested NTFs, is probably the most susceptible and the earliest to decrease in the surviving neurons of SNc. These observations suggest a role for decreased availability of GDNF in the process of SNc neurodegeneration in PD.
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DOI: 10.1016/S0891-0618(01)00115-6
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Lee</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:223CE479F323E30920AD7524CF5BE433F41E17DB</idno><date when="2001" year="2001">2001</date><idno type="doi">10.1016/S0891-0618(01)00115-6</idno><idno type="url">https://api.istex.fr/document/223CE479F323E30920AD7524CF5BE433F41E17DB/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002310</idno><idno type="wicri:Area/Main/Curation">001F93</idno><idno type="wicri:Area/Main/Exploration">001A86</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson's disease brain</title><author><name sortKey="Chauhan, Neelima B" sort="Chauhan, Neelima B" uniqKey="Chauhan N" first="Neelima B" last="Chauhan">Neelima B. Chauhan</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Research and Development Service, Edward Hines, Jr., Veterans Affairs Hospital, Hines, IL 60141</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Siegel, George J" sort="Siegel, George J" uniqKey="Siegel G" first="George J" last="Siegel">George J. Siegel</name><affiliation><wicri:noCountry code="no comma">E-mail: george.siegel@med.va.gov</wicri:noCountry></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neurology Service (127), Edward Hines, Jr., Veterans Affairs Hospital, Hines, IL 60141</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Lee, John M" sort="Lee, John M" uniqKey="Lee J" first="John M" last="Lee">John M. Lee</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Department of Pharmacology and Experimental Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60141</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Chemical Neuroanatomy</title><title level="j" type="abbrev">CHENEU</title><idno type="ISSN">0891-0618</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001">2001</date><biblScope unit="volume">21</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="277">277</biblScope><biblScope unit="page" to="288">288</biblScope></imprint><idno type="ISSN">0891-0618</idno></series><idno type="istex">223CE479F323E30920AD7524CF5BE433F41E17DB</idno><idno type="DOI">10.1016/S0891-0618(01)00115-6</idno><idno type="PII">S0891-0618(01)00115-6</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0891-0618</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aging</term><term>Dopaminergic neurons</term><term>Image analysis</term><term>Immunocytochemistry</term><term>Neuronal loss</term><term>Neurotrophic factors</term><term>Parkinson's disease</term><term>Substantia nigra</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The distribution of nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) in substantia nigra pars compacta (SNc) of Parkinson's disease (PD) brains was investigated by immunofluorescence. Cases studied included four 69–77 year old neurologically normal male controls and four 72–79 year old male PD patients. Integrated optical densities (IODs) of immunofluorescence over individual neuromelanin-containing neurons and in areas of neuropil and the number of neurons on H & E stained adjacent sections were quantitated with the use of the BioQuant Image Analyzer. Data were statistically analyzed by ANOVA, including the unpaired two-tailed Student t-test and the Mann–Whitney test. The results showed 55.8% (P<0.0001) dropout of SNc neurons in PD brains compared to age-matched controls. Despite considerable neuronal dropout, immunofluorescent NTFs in the PD brains showed differential reductions that were consistent within the group as compared to age-matched controls: reductions were GDNF, 19.4%/neuron (P<0.0001), 20.2%/neuropil (P<0.0001); CNTF, 11.1%/neuron (P<0.0001), 9.4%/neuropil (P<0.0001); BDNF, 8.6%/neuron (P<0.0001), 2.5%/neuropil. NGF, NT-3 and NT-4 showed no significant differences within surviving neurons or neuropil. Since the depletion of GDNF both within surviving neurons and neuropil was twice as great as that of CNTF and BDNF and since the other NTFs showed no changes, GDNF, of the tested NTFs, is probably the most susceptible and the earliest to decrease in the surviving neurons of SNc. These observations suggest a role for decreased availability of GDNF in the process of SNc neurodegeneration in PD.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li></region></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Chauhan, Neelima B" sort="Chauhan, Neelima B" uniqKey="Chauhan N" first="Neelima B" last="Chauhan">Neelima B. Chauhan</name></region><name sortKey="Lee, John M" sort="Lee, John M" uniqKey="Lee J" first="John M" last="Lee">John M. Lee</name><name sortKey="Siegel, George J" sort="Siegel, George J" uniqKey="Siegel G" first="George J" last="Siegel">George J. Siegel</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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