alteration of striatal dopaminergic neurotransmission in a mouse model of dyt11 myoclonus-dystonia小鼠模型的变更的纹状体多巴胺能神经传递dyt11 myoclonus-dystonia.pdfVIP

Alteration of Striatal Dopaminergic Neurotransmission in a Mouse Model of DYT11 Myoclonus-Dystonia 1 1 2 2 1 Lin Zhang , Fumiaki Yokoi , Dee S. Parsons , David G. Standaert , Yuqing Li * 1 Department of Neurology, School of Medicine, University of Florida, Gainesville, Florida, United States of America, 2 Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America Abstract Background: DYT11 myoclonus-dystonia (M-D) syndrome is a neurological movement disorder characterized by myoclonic jerks and dystonic postures or movement that can be alleviated by alcohol. It is caused by mutations in SGCE encoding e- sarcoglycan (e-SG); the mouse homolog of this gene is Sgce. Paternally-inherited Sgce heterozygous knockout (Sgce KO) mice exhibit myoclonus, motor impairment and anxiety- and depression-like behaviors, modeling several clinical symptoms observed in DYT11 M-D patients. The behavioral deficits are accompanied by abnormally high levels of dopamine and its metabolites in the striatum of Sgce KO mice. Neuroimaging studies of DYT11 M-D patients show reduced dopamine D2 receptor (D2R) availability, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out. Methodology/Principal Findings: The protein levels of striatal D2R, dopamine transporter (DAT), and dopamine D1 receptor (D1R) in Sgce KO mice were analyzed by Western blot. The striatal dopamine release after amphetamine injection in Sgce KO mice were analyzed by microdialysis in vivo. The striatal D2R was significantly decreased in Sgce KO mice without altering DAT