Analysis of mechanism of LTM-induced cell death in aged brains
| Project/Area Number |
26430030
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurophysiology / General neuroscience
|
|---|
| Research Institution | Tokyo Metropolitan Institute of Medical Science |
|---|
Principal Investigator |
MATSUNO Motomi 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 主席研究員 (90392365)
|
|---|
| Project Period (FY) |
2014-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | 加齢性長期記憶障害 / グリア / グルタミン酸シグナル / カスパーゼ３ / 記憶固定 / ドーパミン作動性神経 / ショウジョウバエ / 長期記憶 / グルタミン酸 / 加齢性記憶障害 / 細胞死 |
|---|
| Outline of Final Research Achievements |
The cellular and molecular mechanisms underlying age-related LTM impairment (LTM-AMI) has been unclear. We previously found that aging inhibits the activity of neuron-glial circuits, which is required for LTM.
Here we show that (1) a defect in the activity of neuron-glial circuits during memory-consolidation suppresses up-regulation of glial glutamate transporter upon LTM induction, causing disinhibition of glutamate signaling. (2)The increase in glutamate signaling results in both hyperactivity and increased caspase3 activation in dopaminergic neurons during consolidation, causing LTM defects. We further found that (3) memory encoding is normal in aged flies. These results suggest that LTM-AMI is not due to a defect of memory encoding, but due to defects in memory consolidation caused by over-excited dopaminergic neurons.
|
| Academic Significance and Societal Importance of the Research Achievements |
若齢脳における長期記憶形成では記憶形成時に上昇したグルタミン酸シグナルを、記憶形成後には一転して抑制する機構があることを示した。一方、加齢個体ではこの抑制機構が機能せず、その結果神経細胞の過剰興奮とアポトーシス関連因子カスパーゼ3活性化が引き起こされ、これがAMIの原因となることを明らかにした。長期記憶がリスクの上で形成されるという概念は新しい概念であり、若い脳にはこのリスクを低下させるグリア細胞を介した仕組みが存在することを示した。本研究で得られた知見はAMI研究および記憶形成におけるグリアの機能について新たな見解を与えると思われる。
|
Report
(7 results)
Research Products
(12 results)
-
-
-
[Journal Article] Glial dysfunction causes age-related memory impairment in Drosophila.2014
Author(s)
Yamazaki D, Horiuchi J, Ueno K, Ueno T, Saeki S, Matsuno M, Naganos S, Miyashita T, Hirano Y, Nishikawa H, Taoka M, Yamauchi Y, Isobe T, Honda Y, Kodama T, Masuda T, Saitoe M
-
Journal Title
Neuron
Volume: 84
Issue: 4
Pages: 753-763
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
