Possible involvement of impaired intrinsic microglial clock in Periodontotis-associated exacerbation of Alzheimer's disease
| Project/Area Number |
18K19650
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 57:Oral science and related fields
|
|---|
| Research Institution | Yasuda Women's University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
倪 軍軍 九州大学, 歯学研究院, 助教 (00783953)
|
|---|
| Project Period (FY) |
2018-06-29 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | ミクログリア / 時計遺伝子 / 炎症性反応 / アルツハイマー病 / ジンジバリス菌 / 網羅的遺伝子解析 / 時計遺伝 / 脳炎症 |
|---|
| Outline of Final Research Achievements |
It is well known that disturbances in clock genes affect almost all patients with Alzheimer’s disease (AD). As microglia-mediated neuroinflammation proved to be a driver of AD rather than a result of the disease, we evaluated the relationship between clock gene disturbance and neuroinflammation in microglia and their contribution to the onset of AD. Pro-inflammatory genes in microglia isolated from APP knock-in mice were significantly higher than those isolated from wild-type mice. The expression of pro-inflammatory genes was positively associated with NF-κB activation and negatively associated with the BMAL1 expression. SR9009 induced the activation of microglia, the increased expression of pro-inflammatory genes, and cognitive decline in APP knock-in mice. Therefore, clock gene disturbance in microglia is involved in the early onset of AD through the induction of chronic neuroinflammation.
|
| Academic Significance and Societal Importance of the Research Achievements |
ミクログリアの活性化反応を活動期に規制するゲート機構が存在し、ミクログリア分子時計の制御下にあることが想定された。本研究ではREV-ERBalphaの発現量がミクログリアの活性化反応を規制するゲート機構の実体であることを突き止めた。さらに、REV-ERBalphaによるミクログリアにおける炎症反応は、Abetaオリゴマーにより促進されることが明らかとなった。本研究成果より、ミクログリアの時計遺伝子（特にREV-ERBalpha）を制御することによりアルツハイマー病に伴う過剰な慢性炎症を抑制できる可能性が示唆される。
|
Report
(4 results)
Research Products
(36 results)
-
-
-
-
-
-
-
-
-
-
[Journal Article] Induction of bone repair in rat calvarial defects using a combination of hydroxyapatite with phosphatidylserine liposomes2019
Author(s)
Hatakeyama J, Anan H, Hatakeyama Y, Matsumoto N, Takayama F, Wu Z, Matsuzaki E, Minakami M, Izumi T, Nakanishi H
-
Journal Title
Journal of Oral Science
Volume: 61
Issue: 1
Pages: 111-118
DOI
NAID
ISSN
1343-4934, 1880-4926
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Pterostilbene, an active component of the dragon’s blood extract, acts as an antiderpressant in adult rats.2019
Author(s)
Yang L, Ran Y, Quan Z, Wang R, Yang Q, Jia Q, Zhang H, Li Y, Peng Y, Liang J, Wang H, Nakanishi H, Deng Y, Qing H.
-
Journal Title
Psychopharmacology (Berl)
Volume: 14
Issue: 4
Pages: 658-665
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
[Journal Article] A Novel Autoantibody against Plexin D1 in Patients with Neuropathic Pain.2018
Author(s)
Fujii T, Yamasaki R, Iinuma K, Tsuchimoto D, Hayashi Y, Saitoh BY, Matsushita T, Kido MA, Aishima S, Nakanishi H, Nakabeppu Y, Kira JI.
-
Journal Title
Annals of Neurology
Volume: 84
Issue: 2
Pages: 208-224
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Manipulation of hippocampal CA3 firing via luminopsins modulates spatial and episodic short-term memory, especially working memory, but not long-term memory.2018
Author(s)
Song D, Yang Q, Lang Y, Wen Z, Xie Z, Zheng D, Yan T, Deng Y, Nakanishi H, Qing H
-
Journal Title
Neurobiol Learn Mem
Volume: 155
Pages: 435-445
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
