1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)　を用いたパーキンソニズム・モデルマウスにおける脳内神経ペプチドに関する研究

1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) has been shown to destroy the nigrostriatal dopaminergic system, inducing biochemical and histopathological changes resembling Parkinson's disease. Biochemical changes, especially changes of neuropeptides were determined 1,2 or 6 weeks after MPTP treatment in various regions of the mice brain. The dopamine (DA) concentration decreased to 22% of the control level in the striatum 1 week after MPTP treatment, but recovered to 50% of the control level 6 weeks after MPTP treatment. The decrease in the noradrenaline concentration was less than that of DA. Amine fluorescence histochemistry revealed, markedly decreased amine fluorescnece in the striatum 6 weeks after MPTP treatment, and this decrease in amine fluorescence was recovered after levodopa treatment. The results of a pole thst revealed the bradykinesia of MPTP-treated mice and it was attenuated b y levodopa and amantadine hydrochloride treatments. Among the neuropeptides tested, somatostatin (SOM) increased 1 week after MPTP treatment in the striatum and the thalamus＋midbrain but decreased 6 weeks after MPTP treatment in the striatum and the hippocampus. In the striatum the decreased SOM recovered with levodopa treatment. Thus, the SOM might be regulated by a dopaminergic system. On the other hand, in the cerebral cortex, while no changes appeared in the SOM concentration after MPTP treatment, the concentration decreased significantly with levodopa treatment. Other neuropeptides such as substance P, cholecystokinin-octapeptide and thyrotropin releasing hormone did not show any significant changes up to 6 weeks after MPTP treatment.

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