title: Alteration of striatal dopaminergic neurotransmission in a mouse model of DYT11 myoclonus-dystonia.
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 ε-sarcoglycan (ε-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.
  
  
  RESULTS
  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 and D1R. Sgce KO mice also exhibited a significant increase of dopamine release after amphetamine injection in comparison to wild-type (WT) littermates.
  
  
  CONCLUSIONS
  The results suggest ε-SG may have a role in the regulation of D2R expression. The loss of ε-SG results in decreased striatal D2R, and subsequently leads to increased discharge of dopamine which could contribute to the behavioral impairment observed in DYT11 dystonia patients and in Sgce KO mice. The results suggest that reduction of striatal D2R and enhanced striatal dopamine release may contribute to the pathophysiology of DYT11 M-D patients.
authors.affiliation: Department of Neurology, School of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Yokoi
authors.forename: Dee S
authors.initials: DS
authors.lastname: Parsons
authors.forename: David G
authors.initials: DG
authors.lastname: Standaert
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Li
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D020821:Dystonic Disorders / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D049031:Sarcoglycans / Q000172:deficiency / Q000235:genetics; D009435:Synaptic Transmission / Q000502:physiology; D014793:Visual Cortex / Q000187:drug effects / Q000503:physiopathology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D049031:Sarcoglycans; D000661:Amphetamine; D004298:Dopamine