Modulation of the basal ganglia dopaminergic system in a transgenic mouse exhibiting dystonia-like features.
Dystonia is a movement disorder characterized by involuntary excessive muscle activity and abnormal postures. There are data supporting the hypothesis that basal ganglia dysfunction, and specifically dopaminergic system dysfunction, plays a role in dystonia. In the present study, we used hyperkinetic transgenic mice generated as a model of DYT1 dystonia and compared the basal ganglia dopaminergic system between transgenic mice exhibiting hyperkinesia (affected), transgenic mice not showing movement abnormalities (unaffected), and non-transgenic littermates. A decrease in the density of striatal D2 binding sites, measured by [³H]raclopride binding, and D2 mRNA expression in substantia nigra pars compacta (SNpc) was revealed in affected and unaffected transgenic mice when compared with non-transgenic. No difference in D1 receptor binding and DAT binding, measured by [³H]SCH23390 and [³H]WIN35428 binding, respectively, was found in striatum of transgenic animals. In SNpc, increased levels of DAT binding sites were observed in affected and unaffected animals compared to non-transgenic, whereas no change in DAT mRNA expression was found. Our results show selective neurochemical changes in the basal ganglia dopaminergic system, suggesting a possible involvement in the pathophysiology of dystonia-like motor hyperactivity.
Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, 26500 Patra, Greece.
Dimitra
D
Giannakopoulou
Ioanna
I
Armata
Ada
A
Mitsacos
Pullani
P
Shashidharan
Panagiotis
P
Giompres
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004421:Dystonia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000378:metabolism* / Q000473:pathology
D004298:Dopamine