Investigation of microglia and chronic stress in the onset of Parkinson disease

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06783
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Nippon Medical School
• Principal Investigator: Sugama Shuei 日本医科大学, 医学部, 講師 (70302461)
• Co-Investigator(Renkei-kenkyūsha): KAKINUMA Yoshihiko 日本医科大学, 大学院医学研究科, 教授 (40233944) ; TAKENOUCHI Takato 国立筑波農業資源研究所, 主任研究員 (20292518) ; HASHIMOTO Makoto 東京都神経科学総合研究所, 副参事研究員 (50189502)
• Research Collaborator: Conti Bruno 米国スクリップス医学研究所, 教授
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 慢性ストレス / パーキンソン病 / ミクログリア / ドーパミン / ノルアドレナリン / 黒質 / 青斑核 / 腹側被蓋野

Outline of Final Research Achievements

In this study, we investigated the effect of chronic stress and microglia in the onset of Parkinson disease. To the best of our knowledge, we report the first evidence that chronic restraint stress in the rat substantially reduces the nigral dopaminergic and locus coeruleus noradrenergic neuronal cells. This reduction was accompanied by robust microglial activation and oxidative stress, marked by nitrotyrosine in the midbrain. These results indicate that chronic stress may trigger the dopaminergic and noradrenergic neurodegeneration by virtue of increased oxidative stress, and that activated microglia, detected in the midbrain, may play an important role in modulating the neurotoxic effects of oxidative stress. Thus, our findings suggest that exposure to chronic stress itself may trigger the dopaminergic and noradrenergic neurodegeneration, a cause of Parkinson disease.

Free Research Field

神経科学