2021 Fiscal Year Final Research Report
Studies of neurodegenerative processes and alpha-synuclein expression focusing on regional specificity of astrocytes.
| Project/Area Number |
19K07993
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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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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
浅沼 幹人 岡山大学, 医歯薬学域, 教授 (00273970)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | パーキンソン病 / α-シヌクレイン / ロテノン / アストロサイト / ミクログリア / ドパミン神経障害 |
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| Outline of Final Research Achievements |
In this study, we revealed that mesencephalic astrocyte-microglia interaction promoted a pesticide rotenone-induced dopaminergic neurotoxicity. In addition, we demonstrated that mesencephalic astrocytes upregulated alpha-synuclein expression in the dopaminergic neurons. We examined secreted molecules from rotenone-treated mesencephalic astrocyte and microglia co-culture by LC-MS/MS analysis. It is demonstrated increase in the inflammatory molecules and decrease in the antioxidants and a protein which inhibits alpha-synuclein aggregation and cell-to-cell propagation. In rotenone-injected parkinsonian mice, we observed alpha-synuclein aggregation and neurodegeneration not only in the central nervous system but also peripheral enteric nervous system. However, change in the alpha-synuclein expression and neurodegeneration are not parallel in some brain region. These results suggest some factors in addition to alpha-synuclein aggregation are involved in region-specific neurodegeneration.
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| Free Research Field |
神経分子病態学，神経病態薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
近年，グリア細胞の部位特異性や神経-グリア連関が注目されつつある．本研究では，アストロサイトの部位特異性が神経細胞でのα-syn発現動態を規定すること，ロテノン誘発ドパミン神経障害においては部位特異的アストロサイト-ミクログリア相互連関が重要であることを明らかにした．また，孤発性パーキンソン病における特定の神経系におけるLewy小体を伴う神経障害機構を解明するためには，アストロサイト-ミクログリア相互連関の部位特異性に着目する必要性があることを提示した．また，本研究でのグリア細胞が部位特異的に分泌する神経障害性分子の同定結果は，今後の神経保護薬開発に寄与しうる．
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