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2019 Fiscal Year Final Research Report

Learning and Memory Performance of Alzheimer Disease Mouse Model with Mutant Human Tau Protein

Research Project

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Project/Area Number 16K08215
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionTokushima Bunri University

Principal Investigator

Kirino Yutaka  徳島文理大学, 薬学部, 教授 (10012668)

Co-Investigator(Kenkyū-buntansha) 窪田 剛志  徳島文理大学, 薬学部, 助教 (90412402)
岸本 泰司  徳島文理大学, 薬学部, 教授 (90441592)
Project Period (FY) 2016-04-01 – 2020-03-31
Keywords生物物理化学 / タウタンパク質 / 神経原線維変化 / 学習と記憶 / 遺伝子変異マウス / アルツハイマー病モデル
Outline of Final Research Achievements

rTg4510 mice constitutively express mutant human tau protein until transgene expression is inactivated by administration of the doxycycline (DOX). In 6-month-old (young) rTg4510 mice, the hippocampus dependent learning abilities including spatial memory, object recognition memory, and trace eyeblink conditioning were impaired. These impairments were reduced by pre-treatment with DOX for 2 months. In parallel, the expression of NFTs decreased in DOX-treated group. 10-month-old (aged) rTg4510 mice showed severe recognition impairment and increased levels of NFTs. Treatment with DOX could not ameliorate the tau pathology in aged rTg4510 mice as well as DOX-untreated group. Since the amount of autophagy markers decreased along with the amelioration of tau pathology, clearance mechanisms of NFTs via autophagy have kept normal functions in 4- to 6-month-old mice while, in 10-month-old mice, clearance system may reach a saturation level.

Free Research Field

物理系薬学

Academic Significance and Societal Importance of the Research Achievements

本研究は、タウタンパク質変異ADモデルマウスにおいて、神経原線維変化(NFT)の程度と学習・記憶障害の程度に強い相関があること、そして、異常タウタンパク質の発現、及び、その結果としてのNFT蓄積を抑制することで、学習・記憶障害を改善できることを示した。これは、最近、われわれとは異なるタイプのタウタンパク変異モデルマウスに対して、鼻腔にタウタンパクに対する抗体ワクチンを投与することにより、病態が改善されたという報告(Takeuchi et al., npj Vaccines, 2020)と一致する。NFTをターゲットとするAD治療法の開発の可能性を示した成果であるという社会的意義を有する。

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Published: 2021-02-19  

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