Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse
Identifieur interne : 000180 ( France/Analysis ); précédent : 000179; suivant : 000181Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse
Auteurs : Jean-Michel Itier ; Pablo Iba N Ez ; Mari A Angeles Mena ; Nacer Abbas ; Charles Cohen-Salmon ; Georg Andrees Bohme ; Michel Laville ; Jeremy Pratt ; Olga Corti ; Laurent Pradier ; Gwe Na Elle Ret ; Chantal Joubert ; Magali Periquet ; Francisco Araujo ; Julia Negroni ; Mari A Jose Casarejos ; Santiago Canals ; Rosa Solano ; Alba Serrano ; Eva Gallego ; Marina Sa Nchez ; Patrice Dene Fle ; Jesu S Benavides ; Gu Nter Tremp ; Thomas A. Rooney ; Alexis Brice [France] ; Justo Garci A De Ye BenesSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2003-09-15.
Abstract
Mutations of the parkin gene are the most frequent cause of early onset autosomal recessive parkinsonism (EO-AR). Here we show that inactivation of the parkin gene in mice results in motor and cognitive deficits, inhibition of amphetamine-induced dopamine release and inhibition of glutamate neurotransmission. The levels of dopamine are increased in the limbic brain areas of parkin mutant mice and there is a shift towards increased metabolism of dopamine by MAO. Although there was no evidence for a reduction of nigrostriatal dopamine neurons in the parkin mutant mice, the level of dopamine transporter protein was reduced in these animals, suggesting a decreased density of dopamine terminals, or adaptative changes in the nigrostriatal dopamine system. GSH levels were increased in the striatum and fetal mesencephalic neurons from parkin mutant mice, suggesting that a compensatory mechanism may protect dopamine neurons from neuronal death. These parkin mutant mice provide a valuable tool to better understand the preclinical deficits observed in patients with PD and to characterize the mechanisms leading to the degeneration of dopamine neurons that could provide new strategies for neuroprotection.
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DOI: 10.1093/hmg/ddg239
Affiliations:
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Rooney</name></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></author><author><name sortKey="Garci A De Ye Benes, Justo" sort="Garci A De Ye Benes, Justo" uniqKey="Garci A De Ye Benes J" first="Justo" last="Garci A De Ye Benes">Justo Garci A De Ye Benes</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:CF16ADEC7627F46229CE703E26898F55B09AFF14</idno><date when="2003" year="2003">2003</date><idno type="doi">10.1093/hmg/ddg239</idno><idno type="url">https://api.istex.fr/document/CF16ADEC7627F46229CE703E26898F55B09AFF14/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001E85</idno><idno type="wicri:Area/Main/Curation">001B95</idno><idno type="wicri:Area/Main/Exploration">001732</idno><idno type="wicri:Area/France/Extraction">000180</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse</title><author><name sortKey="Itier, Jean Michel" sort="Itier, Jean Michel" uniqKey="Itier J" first="Jean-Michel" last="Itier">Jean-Michel Itier</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Iba N Ez, Pablo" sort="Iba N Ez, Pablo" uniqKey="Iba N Ez P" first="Pablo" last="Iba N Ez">Pablo Iba N Ez</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Mena, Mari A Angeles" sort="Mena, Mari A Angeles" uniqKey="Mena M" first="Mari A Angeles" last="Mena">Mari A Angeles Mena</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Abbas, Nacer" sort="Abbas, Nacer" uniqKey="Abbas N" first="Nacer" last="Abbas">Nacer Abbas</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Cohen Salmon, Charles" sort="Cohen Salmon, Charles" uniqKey="Cohen Salmon C" first="Charles" last="Cohen-Salmon">Charles Cohen-Salmon</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Bohme, Georg Andrees" sort="Bohme, Georg Andrees" uniqKey="Bohme G" first="Georg Andrees" last="Bohme">Georg Andrees Bohme</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Laville, Michel" sort="Laville, Michel" uniqKey="Laville M" first="Michel" last="Laville">Michel Laville</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Pratt, Jeremy" sort="Pratt, Jeremy" uniqKey="Pratt J" first="Jeremy" last="Pratt">Jeremy Pratt</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Pradier, Laurent" sort="Pradier, Laurent" uniqKey="Pradier L" first="Laurent" last="Pradier">Laurent Pradier</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Ret, Gwe Na Elle" sort="Ret, Gwe Na Elle" uniqKey="Ret G" first="Gwe Na Elle" last="Ret">Gwe Na Elle Ret</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Joubert, Chantal" sort="Joubert, Chantal" uniqKey="Joubert C" first="Chantal" last="Joubert">Chantal Joubert</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Periquet, Magali" sort="Periquet, Magali" uniqKey="Periquet M" first="Magali" last="Periquet">Magali Periquet</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Araujo, Francisco" sort="Araujo, Francisco" uniqKey="Araujo F" first="Francisco" last="Araujo">Francisco Araujo</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Negroni, Julia" sort="Negroni, Julia" uniqKey="Negroni J" first="Julia" last="Negroni">Julia Negroni</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Casarejos, Mari A Jose" sort="Casarejos, Mari A Jose" uniqKey="Casarejos M" first="Mari A Jose" last="Casarejos">Mari A Jose Casarejos</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Canals, Santiago" sort="Canals, Santiago" uniqKey="Canals S" first="Santiago" last="Canals">Santiago Canals</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Solano, Rosa" sort="Solano, Rosa" uniqKey="Solano R" first="Rosa" last="Solano">Rosa Solano</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Serrano, Alba" sort="Serrano, Alba" uniqKey="Serrano A" first="Alba" last="Serrano">Alba Serrano</name><affiliation><wicri:noCountry code="subField">Spain and</wicri:noCountry></affiliation></author><author><name sortKey="Gallego, Eva" sort="Gallego, Eva" uniqKey="Gallego E" first="Eva" last="Gallego">Eva Gallego</name><affiliation><wicri:noCountry code="subField">Spain and</wicri:noCountry></affiliation></author><author><name sortKey="Sa Nchez, Marina" sort="Sa Nchez, Marina" uniqKey="Sa Nchez M" first="Marina" last="Sa Nchez">Marina Sa Nchez</name><affiliation><wicri:noCountry code="subField">Spain and</wicri:noCountry></affiliation></author><author><name sortKey="Dene Fle, Patrice" sort="Dene Fle, Patrice" uniqKey="Dene Fle P" first="Patrice" last="Dene Fle">Patrice Dene Fle</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Benavides, Jesu S" sort="Benavides, Jesu S" uniqKey="Benavides J" first="Jesu S" last="Benavides">Jesu S Benavides</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Tremp, Gu Nter" sort="Tremp, Gu Nter" uniqKey="Tremp G" first="Gu Nter" last="Tremp">Gu Nter Tremp</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Rooney, Thomas A" sort="Rooney, Thomas A" uniqKey="Rooney T" first="Thomas A." last="Rooney">Thomas A. Rooney</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Département de Génétique, Cytogénétique et Embryologie, Groupe Hopitalier Pitié-Salpêtrière, AP-HP, 47, Bd de l'Hôpital, 75651 Paris Cedex 13</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Garci A De Ye Benes, Justo" sort="Garci A De Ye Benes, Justo" uniqKey="Garci A De Ye Benes J" first="Justo" last="Garci A De Ye Benes">Justo Garci A De Ye Benes</name><affiliation><wicri:noCountry code="subField">Spain and</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><title level="j" type="abbrev">Hum. Mol. Genet.</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2003-09-15">2003-09-15</date><biblScope unit="volume">12</biblScope><biblScope unit="issue">18</biblScope><biblScope unit="page" from="2277">2277</biblScope><biblScope unit="page" to="2291">2291</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">CF16ADEC7627F46229CE703E26898F55B09AFF14</idno><idno type="DOI">10.1093/hmg/ddg239</idno><idno type="local">ddg239</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations of the parkin gene are the most frequent cause of early onset autosomal recessive parkinsonism (EO-AR). Here we show that inactivation of the parkin gene in mice results in motor and cognitive deficits, inhibition of amphetamine-induced dopamine release and inhibition of glutamate neurotransmission. The levels of dopamine are increased in the limbic brain areas of parkin mutant mice and there is a shift towards increased metabolism of dopamine by MAO. Although there was no evidence for a reduction of nigrostriatal dopamine neurons in the parkin mutant mice, the level of dopamine transporter protein was reduced in these animals, suggesting a decreased density of dopamine terminals, or adaptative changes in the nigrostriatal dopamine system. GSH levels were increased in the striatum and fetal mesencephalic neurons from parkin mutant mice, suggesting that a compensatory mechanism may protect dopamine neurons from neuronal death. These parkin mutant mice provide a valuable tool to better understand the preclinical deficits observed in patients with PD and to characterize the mechanisms leading to the degeneration of dopamine neurons that could provide new strategies for neuroprotection.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Abbas, Nacer" sort="Abbas, Nacer" uniqKey="Abbas N" first="Nacer" last="Abbas">Nacer Abbas</name><name sortKey="Araujo, Francisco" sort="Araujo, Francisco" uniqKey="Araujo F" first="Francisco" last="Araujo">Francisco Araujo</name><name sortKey="Benavides, Jesu S" sort="Benavides, Jesu S" uniqKey="Benavides J" first="Jesu S" last="Benavides">Jesu S Benavides</name><name sortKey="Bohme, Georg Andrees" sort="Bohme, Georg Andrees" uniqKey="Bohme G" first="Georg Andrees" last="Bohme">Georg Andrees Bohme</name><name sortKey="Canals, Santiago" sort="Canals, Santiago" uniqKey="Canals S" first="Santiago" last="Canals">Santiago Canals</name><name sortKey="Casarejos, Mari A Jose" sort="Casarejos, Mari A Jose" uniqKey="Casarejos M" first="Mari A Jose" last="Casarejos">Mari A Jose Casarejos</name><name sortKey="Cohen Salmon, Charles" sort="Cohen Salmon, Charles" uniqKey="Cohen Salmon C" first="Charles" last="Cohen-Salmon">Charles Cohen-Salmon</name><name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name><name sortKey="Dene Fle, Patrice" sort="Dene Fle, Patrice" uniqKey="Dene Fle P" first="Patrice" last="Dene Fle">Patrice Dene Fle</name><name sortKey="Gallego, Eva" sort="Gallego, Eva" uniqKey="Gallego E" first="Eva" last="Gallego">Eva Gallego</name><name sortKey="Garci A De Ye Benes, Justo" sort="Garci A De Ye Benes, Justo" uniqKey="Garci A De Ye Benes J" first="Justo" last="Garci A De Ye Benes">Justo Garci A De Ye Benes</name><name sortKey="Iba N Ez, Pablo" sort="Iba N Ez, Pablo" uniqKey="Iba N Ez P" first="Pablo" last="Iba N Ez">Pablo Iba N Ez</name><name sortKey="Itier, Jean Michel" sort="Itier, Jean Michel" uniqKey="Itier J" first="Jean-Michel" last="Itier">Jean-Michel Itier</name><name sortKey="Joubert, Chantal" sort="Joubert, Chantal" uniqKey="Joubert C" first="Chantal" last="Joubert">Chantal Joubert</name><name sortKey="Laville, Michel" sort="Laville, Michel" uniqKey="Laville M" first="Michel" last="Laville">Michel Laville</name><name sortKey="Mena, Mari A Angeles" sort="Mena, Mari A Angeles" uniqKey="Mena M" first="Mari A Angeles" last="Mena">Mari A Angeles Mena</name><name sortKey="Negroni, Julia" sort="Negroni, Julia" uniqKey="Negroni J" first="Julia" last="Negroni">Julia Negroni</name><name sortKey="Periquet, Magali" sort="Periquet, Magali" uniqKey="Periquet M" first="Magali" last="Periquet">Magali Periquet</name><name sortKey="Pradier, Laurent" sort="Pradier, Laurent" uniqKey="Pradier L" first="Laurent" last="Pradier">Laurent Pradier</name><name sortKey="Pratt, Jeremy" sort="Pratt, Jeremy" uniqKey="Pratt J" first="Jeremy" last="Pratt">Jeremy Pratt</name><name sortKey="Ret, Gwe Na Elle" sort="Ret, Gwe Na Elle" uniqKey="Ret G" first="Gwe Na Elle" last="Ret">Gwe Na Elle Ret</name><name sortKey="Rooney, Thomas A" sort="Rooney, Thomas A" uniqKey="Rooney T" first="Thomas A." last="Rooney">Thomas A. Rooney</name><name sortKey="Sa Nchez, Marina" sort="Sa Nchez, Marina" uniqKey="Sa Nchez M" first="Marina" last="Sa Nchez">Marina Sa Nchez</name><name sortKey="Serrano, Alba" sort="Serrano, Alba" uniqKey="Serrano A" first="Alba" last="Serrano">Alba Serrano</name><name sortKey="Solano, Rosa" sort="Solano, Rosa" uniqKey="Solano R" first="Rosa" last="Solano">Rosa Solano</name><name sortKey="Tremp, Gu Nter" sort="Tremp, Gu Nter" uniqKey="Tremp G" first="Gu Nter" last="Tremp">Gu Nter Tremp</name></noCountry><country name="France"><region name="Île-de-France"><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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