Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial parkinsonism-linked gene DJ-1

Matthew S. Goldberg, Antonio Pisani, Marian Haburcak, Timothy A. Vortherms, Tohru Kitada, Cinzia Costa, Youren Tong, Giuseppina Martella, Anne Tscherter, Andrea Martins, Giorgio Bernardi, Bryan L. Roth, Emmanuel N. Pothos, Paolo Calabresi, Jie Shen

Research output: Contribution to journalArticlepeer-review

Abstract

The manifestations of Parkinson's disease are caused by reduced dopaminergic innervation of the striatum. Loss-of-function mutations in the DJ-1 gene cause early-onset familial parkinsonism. To investigate a possible role for DJ-1 in the dopaminergic system, we generated a mouse model bearing a germline disruption of DJ-1. Although DJ-1-/- mice had normal numbers of dopaminergic neurons in the substantia nigra, evoked dopamine overflow in the striatum was markedly reduced, primarily as a result of increased reuptake. Nigral neurons lacking DJ-1 were less sensitive to the inhibitory effects of D2 autoreceptor stimulation. Corticostriatal long-term potentiation was normal in medium spiny neurons of DJ-1-/- mice, but long-term depression (LTD) was absent. The LTD deficit was reversed by treatment with D2 but not D1 receptor agonists. Furthermore, DJ-1-/- mice displayed hypoactivity in the open field. Collectively, our findings suggest an essential role for DJ-1 in dopaminergic physiology and D2 receptor-mediated functions.

Original languageEnglish
Pages (from-to)489-496
Number of pages8
JournalNeuron
Volume45
Issue number4
DOIs
Publication statusPublished - Feb 17 2005

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial parkinsonism-linked gene DJ-1'. Together they form a unique fingerprint.

Cite this