Involvement of brain pericytes in alpha-synuclein-induced dysfunction of the blood-brain barrier and dopaminergic neurons
| Project/Area Number |
16K08566
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Fukuoka University |
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Principal Investigator |
DOHGU Shinya 福岡大学, 薬学部, 准教授 (60399186)
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| Co-Investigator(Kenkyū-buntansha) |
高田 芙友子 福岡大学, 薬学部, 助教 (70412575)
山内 淳史 福岡大学, 薬学部, 教授 (90341453)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 脳ペリサイト / αシヌクレイン / 血液脳関門 / 炎症性サイトカイン / ドパミン神経 / オートファジー / パーキンソン病 / ドパミン神経細胞 / 神経細胞 / 6-hydroxydopamine |
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| Outline of Final Research Achievements |
Parkinson’s disease (PD) is characterized by widespread distribution of aggregated α-synuclein (α-Syn) protein in inclusions known as Lewy bodies and loss of dopaminergic neurons in substantia nigra. α-Syn is secreted from neurons and transferred to neighboring cells. This cell-to-cell transmission of α-Syn is thought to underlie the progress of PD. In addition, disruption of the BBB occurred in the patients with PD. Here, we investigated whether brain pericytes is involved in loss of dopaminergic neurons and BBB disruption in PD.
Brain pericytes inhibited dopaminergic neuronal cell death by decreasing expression of the cleaved caspase-3. Pericytes up-regulate the activity of dopaminergic neurons in healthy condition.
Brain pericytes are sensitive to monomeric α-Syn in terms of the release of various inflammatory cytokines/chemokines and MMP-9 leading to BBB dysfunction. α-Syn-reactive pericytes could contribute to dysfunction of dopaminergic neurons and BBB in patient with PD.
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| Academic Significance and Societal Importance of the Research Achievements |
血液脳関門機能低下と認知機能障害が相関することが明らかにされており、αシヌクレインによって誘発される血液脳関門機能破綻が認知機能障害誘発に繋がるかもしれない。さらに、αシヌクレイン単量体はペリサイトのドパミン神経機能亢進作用の抑制因子でもある。一方で、脳ペリサイトはαシヌクレインを細胞内へ取り込み、分解することで、脳内での過剰なαシヌクレイン蓄積を抑制しているかもしれない。従って、脳ペリサイトの機能低下はαシヌクレイン病態の加速因子となり得る。今後in vivoでの検討が必要であるが、ペリサイトがαシヌクレイン病態を解明する鍵になる可能性がある。
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Report
(4 results)
Research Products
(10 results)
