Effects of a neurotoxin DSP-4 on pathogenesis in a mouse model of tauopathy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K14343
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: YOSHIDA Hirotaka 国立研究開発法人国立長寿医療研究センター, 共同利用推進室, 研究生 (70646570)
• Co-Investigator(Kenkyū-buntansha): 木村 哲也 国立研究開発法人国立長寿医療研究センター, アルツハイマー病研究部, 室長 (00415142)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: タウ / タウオパチー / 認知症 / ノルアドレナリン / 神経毒

Outline of Final Research Achievements

A reduction of level of noradrenalin in cortex, hippocampus and entorhinal cortex by a neurotoxin DSP-4 induced a spread of tau pathology to these regions in an earlier stage in a pathological process and a reduction of survival rate in a transgenic mouse model of tauopathy, expressing P301S mutant tau protein. The results suggested that the reduction of the level of noradrenalin and its effects on neuronal activity in brain enhance the aging and the pathogenesis of tauopathy in the model mouse line. In addition, extracellular tau was labeled by oligomer- and conformation-dependent anti-tau antibodies more than intracellular tau, indicating that immunochemical approach using these antibodies are useful for further study for a molecular mechanism of progression of tau pathology.

Free Research Field

神経科学