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論文
- タイトル
- タイトル（英）
- Establishment and Use of Primary Cultured Astrocytes from Alexander Disease Model Mice
- 参照URL
- https://researchmap.jp/read0091842/published_papers/49486003
- 著者
- 著者（英）
- Yuto Kubota,Eiji Shigetomi,Kozo Saito,Youichi Shinozaki,Kenji Kobayashi,Masayoshi Tanaka,Bijay Parajuli,Kenji F. Tanaka,Schuichi Koizumi
- 担当区分
- 概要
- 概要（英）
- Alexander disease (AxD) is an intractable neurodegenerative disease caused by mutations in glial fibrillary acidic protein (GFAP), which is predominantly expressed in astrocytes. Thus, AxD is a primary astrocyte disease. However, it remains unclear how GFAP mutations affect astrocytes and cause AxD pathology. Three features are characteristic of AxD astrocytes in vivo: (1) Rosenthal fibers (RFs), the hallmark of AxD; (2) aberrant Ca2+ signals (AxCa); and (3) upregulation of disease-associated genes (AxGen). We established a primary culture system for astrocytes from an AxD transgenic mouse model, and used it to analyze the above features of AxD pathogenesis in astrocytes in vitro. We observed the formation of RFs in AxD primary cultures. The abundance of RFs was greater in AxD-transgene-homozygous compared with -hemizygous astrocytes, indicating a gene dosage effect, and this abundance increased with time in culture, indicating a developmental process effect. However, cultured AxD astrocytes did not exhibit changes in either AxCa or AxGen. We therefore conclude that RFs in astrocytes form via a cell-autonomous mechanism, whereas AxCa and AxGen are likely to occur via a non-cell-autonomous mechanism through interactions with other cells, such as neurons, microglia, and vascular cells. Although primary cultured AxD astrocytes are suitable for elucidating the mechanisms of RFs formation and for intervention studies, it should be noted that they cannot reflect the pathophysiology of non-cell-autonomous events in astrocytes.
- 出版者・発行元
- 出版者・発行元（英）
- MDPI AG
- 誌名
- 誌名（英）
- International Journal of Molecular Sciences
- 巻
- 25
- 号
- 22
- 開始ページ
- 12100
- 終了ページ
- 12100
- 出版年月
- 2024年11月11日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.3390/ijms252212100
- 共同研究・競争的資金等の研究課題
研究者
篠﨑 陽一
(シノザキ ヨウイチ)