Elucidation of molecular mechanisms of neurodegeneration caused by dysfunctional senescent astrocytes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kagawa University
• Principal Investigator: Chiba Yoichi 香川大学, 医学部, 准教授 (30372113)
• Co-Investigator(Kenkyū-buntansha): 古川 絢子 鈴鹿医療科学大学, 薬学部, 助教 (10455537) ; 上野 正樹 香川大学, 医学部, 教授 (30322267)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 神経変性疾患 / 細胞老化 / アストロサイト / プロテオミクス

Outline of Final Research Achievements

There is an increasing awareness of the contribution of senescent cells to age-related pathologies. Recent studies suggested astrocytes exhibit cellular senescence phenotypes in aged human brain and Alzheimer’s disease. However, the mechanisms that　senescent astrocytes affect pathophysiology of brain aging and age-related neurodegenerative diseases remain unclear. Here we investigated changes in protein expression in senescent astrocyte using 2-dimensional fluorescence difference gel electrophoresis (2D-DIGE). Cellular senescence, assessed by senescence-associated β-galactosidase (SA-β-Gal) staining, immunoblotting with p21 and lamin B1 antibodies, and γH2AX immunocytochemistry, was efficiently induced by treating mouse primary astrocytes with 200 μM H2O2 for 2 hours. 2D-DIGE analyses revealed that 5 protein spots showed a significant increase in H2O2-treated astrocytes compared with control, whereas 6 spots exhibited significant decrease in H2O2-treated cells.

Free Research Field

神経病理学

Academic Significance and Societal Importance of the Research Achievements

細胞老化は、老化関連疾患の基盤にある現象として近年注目されている。我が国で今後患者数の増加が予想されるアルツハイマー病やパーキンソン病などの加齢性神経変性疾患においても、細胞老化が関わる可能性が示唆されている。アストロサイトは細胞老化関連分泌形質（SASP）因子を発現しうる細胞であり、脳の加齢性変化に密接に関わっている可能性が高い。我々は、老化アストロサイトの形質の変化を蛋白質発現変化の観点から明らかにした。本研究の成果は今後加齢性神経変性疾患の予防や新しい治療を考える上で基盤となる知見をもたらすものと考えられる。