Learning and Memory Performance of Alzheimer Disease Mouse Model with Mutant Human Tau Protein
| Project/Area Number |
16K08215
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Physical pharmacy
|
|---|
| Research Institution | Tokushima 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
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| 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 / 瞬目反射条件付け / モリス水迷路試験 / 新奇物体探索試験 / アルツハイマー病 / 学習・記憶 / 認知障害 / 行動神経科学 / マウスモデル |
|---|
| 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.
|
| 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。
|
Report
(5 results)
Research Products
(21 results)
-
-
-
[Journal Article] Loss of synapse repressor MDGA1 enhances perisomatic inhibition, confers resistance to network excitation, and impairs cognitive function2017
Author(s)
Steven A. Connor, Ina Ammendrup-Johnsen, Yasushi Kishimoto, Parisa Karimi Tari, Vedrana Cvetkovska, Takashi Harada, Daiki Ojima, Tohru Yamamoto, Yu Tian Wang, Ann Marie Craig
-
Journal Title
Cell Rep.
Volume: 26
Issue: 13
Pages: 3637-3645
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Altered Cortical Dynamics and Cognitive Function upon Haploinsufficiency of the Autism-Linked Excitatory Synaptic Suppressor MDGA2.2016
Author(s)
Steven A. Connor*, Ina Ammendrup-Johnsen*, Allen W. Chan*, Yasushi Kishimoto*, Chiaki Murayama, Naokazu Kurihara, Atsushi Tada, Yuan Ge, Hong Lu, Ryan Yan, Jeffrey M. LeDue, Hirotaka Matsumoto, Hiroshi Kiyonari, Yutaka Kirino,... Tohru Yamamoto, Ann Marie Craig.
-
Journal Title
Neuron
Volume: 91
Pages: 1052-2068
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
