Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1 - PubMed (original) (raw)
Comparative Study
. 2005 Feb 17;45(4):489-96.
doi: 10.1016/j.neuron.2005.01.041.
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
Affiliations
- PMID: 15721235
- DOI: 10.1016/j.neuron.2005.01.041
Free article
Comparative Study
Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1
Matthew S Goldberg et al. Neuron. 2005.
Free article
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.
Comment in
- Without DJ-1, the D2 receptor doesn't play.
Borrelli E. Borrelli E. Neuron. 2005 Feb 17;45(4):479-81. doi: 10.1016/j.neuron.2005.02.004. Neuron. 2005. PMID: 15721232 Review.
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