Modelling Parkinson-like neurodegeneration via osmotic minipump delivery of MPTP and probenecid.
Identifieur interne : 000C04 ( PubMed/Checkpoint ); précédent : 000C03; suivant : 000C05Modelling Parkinson-like neurodegeneration via osmotic minipump delivery of MPTP and probenecid.
Auteurs : Daniel Alvarez-Fischer [France] ; Serge Guerreiro ; Stéphane Hunot ; Françoise Saurini ; Marc Marien ; Pierre Sokoloff ; Etienne C. Hirsch ; Andreas Hartmann ; Patrick P. MichelSource :
- Journal of neurochemistry [ 1471-4159 ] ; 2008.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (administration & dosage), Adjuvants, Pharmaceutic (administration & dosage), Animals, Brain (drug effects), Brain (pathology), Chromatography, High Pressure Liquid, Disease Models, Animal, Dopamine (analysis), Dopamine (metabolism), Immunohistochemistry, Infusion Pumps, Male, Mice, Mice, Inbred C57BL, Nerve Degeneration (chemically induced), Neurotoxins (administration & dosage), Parkinsonian Disorders (chemically induced), Probenecid (administration & dosage).
- MESH :
- chemical , administration & dosage : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Adjuvants, Pharmaceutic, Neurotoxins, Probenecid.
- chemical , analysis : Dopamine.
- chemically induced : Nerve Degeneration, Parkinsonian Disorders.
- drug effects : Brain.
- chemical , metabolism : Dopamine.
- pathology : Brain.
- Animals, Chromatography, High Pressure Liquid, Disease Models, Animal, Immunohistochemistry, Infusion Pumps, Male, Mice, Mice, Inbred C57BL.
Abstract
Mouse models of MPTP intoxication have been used extensively to explore the molecular mechanisms of Parkinson's disease. However, these models present some limitations since; (i) Dopaminergic (DA) cell death occurs rapidly in contrast to the presumably slow evolution of the disease process. (ii) Some of the key histological features of the disease such as Lewy body like inclusions and long-term inflammatory changes are lacking. Fornai et al. [Proc. Natl Acad. Sci. USA 102 (2005), 3413] suggested that continuous delivery of MPTP with Alzet osmotic minipumps may possibly circumvent these problems. Our results show, however, that MPTP infusion via Alzet osmotic minipumps (40 mg/kg/day) produces only a transient depletion in striatal dopamine (DA) without causing dopaminergic cell loss in the substantia nigra. Neuronal cell loss occurred, however, if MPTP was infused concomitantly with probenecid, an uricosuric agent which potentiates the effects of the toxin injected via the i.p. route. Even under these conditions, dopaminergic cell loss was moderate (-25%) and other neurodegenerative changes characteristic of Parkinson's disease remained undetectable.
DOI: 10.1111/j.1471-4159.2008.05651.x
PubMed: 18761710
Affiliations:
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Hirsch</name></author><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P" last="Michel">Patrick P. Michel</name></author></analytic><series><title level="j">Journal of neurochemistry</title><idno type="eISSN">1471-4159</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (administration & dosage)</term><term>Adjuvants, Pharmaceutic (administration & dosage)</term><term>Animals</term><term>Brain (drug effects)</term><term>Brain (pathology)</term><term>Chromatography, High Pressure Liquid</term><term>Disease Models, Animal</term><term>Dopamine (analysis)</term><term>Dopamine (metabolism)</term><term>Immunohistochemistry</term><term>Infusion Pumps</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Nerve Degeneration (chemically induced)</term><term>Neurotoxins (administration & dosage)</term><term>Parkinsonian Disorders (chemically induced)</term><term>Probenecid (administration & dosage)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Adjuvants, Pharmaceutic</term><term>Neurotoxins</term><term>Probenecid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Nerve Degeneration</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chromatography, High Pressure Liquid</term><term>Disease Models, Animal</term><term>Immunohistochemistry</term><term>Infusion Pumps</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mouse models of MPTP intoxication have been used extensively to explore the molecular mechanisms of Parkinson's disease. However, these models present some limitations since; (i) Dopaminergic (DA) cell death occurs rapidly in contrast to the presumably slow evolution of the disease process. (ii) Some of the key histological features of the disease such as Lewy body like inclusions and long-term inflammatory changes are lacking. Fornai et al. [Proc. Natl Acad. Sci. USA 102 (2005), 3413] suggested that continuous delivery of MPTP with Alzet osmotic minipumps may possibly circumvent these problems. Our results show, however, that MPTP infusion via Alzet osmotic minipumps (40 mg/kg/day) produces only a transient depletion in striatal dopamine (DA) without causing dopaminergic cell loss in the substantia nigra. Neuronal cell loss occurred, however, if MPTP was infused concomitantly with probenecid, an uricosuric agent which potentiates the effects of the toxin injected via the i.p. route. Even under these conditions, dopaminergic cell loss was moderate (-25%) and other neurodegenerative changes characteristic of Parkinson's disease remained undetectable.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">18761710</PMID><DateCreated><Year>2008</Year><Month>11</Month><Day>07</Day></DateCreated><DateCompleted><Year>2008</Year><Month>12</Month><Day>16</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1471-4159</ISSN><JournalIssue CitedMedium="Internet"><Volume>107</Volume><Issue>3</Issue><PubDate><Year>2008</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Journal of neurochemistry</Title><ISOAbbreviation>J. 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Our results show, however, that MPTP infusion via Alzet osmotic minipumps (40 mg/kg/day) produces only a transient depletion in striatal dopamine (DA) without causing dopaminergic cell loss in the substantia nigra. Neuronal cell loss occurred, however, if MPTP was infused concomitantly with probenecid, an uricosuric agent which potentiates the effects of the toxin injected via the i.p. route. Even under these conditions, dopaminergic cell loss was moderate (-25%) and other neurodegenerative changes characteristic of Parkinson's disease remained undetectable.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alvarez-Fischer</LastName><ForeName>Daniel</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S679, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guerreiro</LastName><ForeName>Serge</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Hunot</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Saurini</LastName><ForeName>Françoise</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Marien</LastName><ForeName>Marc</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Sokoloff</LastName><ForeName>Pierre</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Hirsch</LastName><ForeName>Etienne C</ForeName><Initials>EC</Initials></Author><Author ValidYN="Y"><LastName>Hartmann</LastName><ForeName>Andreas</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Michel</LastName><ForeName>Patrick P</ForeName><Initials>PP</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2008</Year><Month>09</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Neurochem</MedlineTA><NlmUniqueID>2985190R</NlmUniqueID><ISSNLinking>0022-3042</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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IdType="doi">10.1111/j.1471-4159.2008.05651.x</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Guerreiro, Serge" sort="Guerreiro, Serge" uniqKey="Guerreiro S" first="Serge" last="Guerreiro">Serge Guerreiro</name><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C" last="Hirsch">Etienne C. Hirsch</name><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name><name sortKey="Marien, Marc" sort="Marien, Marc" uniqKey="Marien M" first="Marc" last="Marien">Marc Marien</name><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P" last="Michel">Patrick P. Michel</name><name sortKey="Saurini, Francoise" sort="Saurini, Francoise" uniqKey="Saurini F" first="Françoise" last="Saurini">Françoise Saurini</name><name sortKey="Sokoloff, Pierre" sort="Sokoloff, Pierre" uniqKey="Sokoloff P" first="Pierre" last="Sokoloff">Pierre Sokoloff</name></noCountry><country name="France"><region name="Île-de-France"><name sortKey="Alvarez Fischer, Daniel" sort="Alvarez Fischer, Daniel" uniqKey="Alvarez Fischer D" first="Daniel" last="Alvarez-Fischer">Daniel Alvarez-Fischer</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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