Microglia-astrocyte crosstalk in leukoencephalopathies

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07972
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Niigata University
• Principal Investigator: Tada Mari 新潟大学, 脳研究所, 准教授 (30646394)
• Co-Investigator(Kenkyū-buntansha): 池内 健 新潟大学, 脳研究所, 教授 (20372469) ; 竹林 浩秀 新潟大学, 医歯学系, 教授 (60353439) ; 加藤 隆弘 九州大学, 大学病院, 講師 (70546465) ; 柿田 明美 新潟大学, 脳研究所, 教授 (80281012)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: microglia / astrocyte / ALSP / TGFβ / C3d

Outline of Final Research Achievements

We have previously reported that in the brains of patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), an inherited leukoencephalopathy caused by mutations in the colony stimulating factor 1 receptor (CSF1R) gene, the increase of inflammatory microglia is small in number and restricted in area relative to the degree of widespread white matter degeneration, whereas the decrease of homeostatic microglia is significant. In this study, we examined the correlation between the distribution of astrocytes and microglia in the cerebral white matter of ALSP. Our findings support the hypothesis that disruption of microglial control over astrocytes due to microglial dysfunction induces abnormal activation of astrocytes, leading to accelerated white matter degeneration.

Free Research Field

神経病理学

Academic Significance and Societal Importance of the Research Achievements

CSF1Rの遺伝子変異による遺伝性白質脳症、Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) を対象として組織学的に解析を進め、大脳白質維持においてミクログリアとアストロサイトが相関して役割を果たしている可能性を示した。大脳白質の恒常性維持機構の解明はアルツハイマー病などの加齢に伴い認知症をきたす疾患において極めて重要な課題であり、本研究で得られた知見はその足がかりとなり得る。