Differential regulation of striatal G protein levels following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration in C57 BL/6 mice.
The dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to produce a severe Parkinsonian state in both humans and animals. Unlike idiopathic Parkinson's disease, however, most MPTP models show some degree of behavioral recovery with time. Here we report that stimulatory G proteins are differentially regulated in the striatum of C57 BL/6 mice following systemic MPTP administration. As measured by Western blotting, the striatal stimulatory G proteins Gs and Golf were reduced by 20% and 25% at 10 days following cessation of MPTP treatment, despite a significant impairment in striatal dopamine levels (<90% reduction). Conversely, Gs and Golf levels were upregulated by 15% and 30% at 10 months following MPTP withdrawal. No change was observed in striatal inhibitory G proteins or any cortical G protein at any time post-treatment. These results suggest that G protein upregulation may play a role in mediating behavioral recovery following MPTP administration.
Marcotte
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Department of Psychiatry, Faculty of Health Sciences, McMaster University, Hamilton, L8N 3Z5, Ontario, Canada. mishrar@mcmaster.ca
Chugh
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A
Barlas
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Mishra
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RK
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019204:GTP-Binding Proteins