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Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer’s disease
https://repo.qst.go.jp/records/81530
https://repo.qst.go.jp/records/815305ddd31b4-cd64-49f1-8581-584d083b0090
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-01-05 | |||||
| タイトル | ||||||
| タイトル | Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer’s disease | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Sobue, Akira
× Sobue, Akira× Komine, Okiru× Hara, Yuichiro× Endo, Fumito× Mizoguchi, Hiroyuki× Watanabe, Seiji× Murayama, Shigeo× Saito, Takashi× C. Saido, Takaomi× Sahara, Naruhiko× Higuchi, Makoto× Ogi, Tomoo× Yamanaka, Koji× Naruhiko, Sahara× Makoto, Higuchi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Microglia-mediated neuroinflammation has been implicated in the pathogenesis of Alzheimer’s disease (AD). Although microglia in aging and neurodegenerative disease model mice show a loss of homeostatic phenotype and activation of disease-associated microglia (DAM), a correlation between those phenotypes and the degree of neuronal cell loss has not been clarified. In this study, we performed RNA sequencing of microglia isolated from three representative neurodegenerative mouse models, AppNL-G-F/NL-G-F with amyloid pathology, rTg4510 with tauopathy, and SOD1G93A with motor neuron disease by magnetic activated cell sorting. In parallel, gene expression patterns of the human precuneus with early Alzheimer’s change (n = 11) and control brain (n = 14) were also analyzed by RNA sequencing. We found that a substantial reduction of homeostatic microglial genes in rTg4510 and SOD1G93A microglia, whereas DAM genes were uniformly upregulated in all mouse models. The reduction of homeostatic microglial genes was correlated with the degree of neuronal cell loss. In human precuneus with early AD pathology, reduced expression of genes related to microglia- and oligodendrocyte-specific markers was observed, although the expression of DAM genes was not upregulated. Our results implicate a loss of homeostatic microglial function in the progression of AD and other neurodegenerative diseases. Moreover, analyses of human precuneus also suggest loss of microglia and oligodendrocyte functions induced by early amyloid pathology in human |
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| 書誌情報 |
Acta Neuropathologica Communications 巻 9, 号 1, p. 1, 発行日 2021-01 |
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| 出版者 | ||||||
| 出版者 | BMC | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2051-5960 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 33402227 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1186/s40478-020-01099-x | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-020-01099-x | |||||
