Modulation of torsinA expression in the globus pallidus internus is associated with levodopa-induced dyskinesia in hemiparkinsonian rats.
TorsinA is the causative protein of DYT1 dystonia, a major representative of hyperkinetic movement disorders. In this study, the distribution of torsinA was investigated in the basal ganglia of hemiparkinsonian rats with or without levodopa-induced dyskinesia (LID). Two months after 6-hydroxydopamine (OHDA) treatment, Wistar-albino rats were subjected to intermittent intraperitoneal injection of levodopa/benserazid (LID-group, n=5) or vehicle (control, n=5) for 21 days. Immunohistochemical analysis disclosed that in the caudal portion of the entopeduncular nucleus (EP), homologous to the globus pallidus internus (GPi) in primates, on the parkinsonian side, there was a significant decrease of torsinA-immunopositive neurons in rats with LID, but not in those without LID. However, Nissl-staining showed no loss of GPi neurons in rats with LID. In both groups, there was no significant difference between ipsi- and contralateral sides with respect to the density of torsinA-positive neuronal cells in the striatum, globus pallidus externus, and subthalamic nucleus. Ours are the first data to demonstrate the specific modulation of torsinA expression in the basal ganglia of the hyperkinesia model, suggesting that GPi neurons containing torsinA possess pathologic plasticity for LID.
Yamada
Kazumichi
K
Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Goto
Satoshi
S
Kaji
Ryuji
R
Kuratsu
Jun-ichi
J
D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000009:adverse effects; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism* / Q000503:physiopathology; D020392:Entopeduncular Nucleus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D018832:Molecular Chaperones / Q000187:drug effects / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D015259:Dopamine Agents; D018832:Molecular Chaperones; C491549:Tor1a protein, rat; D007980:Levodopa; D016627:Oxidopamine