Journal Article

Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse

Jean-Michel Itier, Pablo Ibáñez, María Angeles Mena, Nacer Abbas, Charles Cohen-Salmon, Georg Andrees Bohme, Michel Laville, Jeremy Pratt, Olga Corti, Laurent Pradier, Gwénäelle Ret, Chantal Joubert, Magali Periquet, Francisco Araujo, Julia Negroni, María José Casarejos, Santiago Canals, Rosa Solano, Alba Serrano, Eva Gallego, Marina Sánchez, Patrice Denèfle, Jesús Benavides, Günter Tremp, Thomas A. Rooney, Alexis Brice and Justo García de Yébenes

in Human Molecular Genetics

Volume 12, issue 18, pages 2277-2291
Published in print September 2003 | ISSN: 0964-6906
Published online September 2003 | e-ISSN: 1460-2083 | DOI:
Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse

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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.

Journal Article.  11491 words.  Illustrated.

Subjects: Genetics and Genomics

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