Division of Biomedical Sciences and Biomedical Sciences Graduate Program, School of Medicine, University of California Riverside, Riverside, California, USA.
Neuroscience Graduate Program, University of California Riverside, Riverside, California, USA.
ASN Neuro. 2024;16(1):2401753. doi: 10.1080/17590914.2024.2401753. Epub 2024 Oct 22.
Astrocytes have been implicated in oligodendrocyte development and myelination, however, the mechanisms by which astrocytes regulate oligodendrocytes remain unclear. Our findings suggest a new mechanism that regulates astrocyte-mediated oligodendrocyte development through ephrin-B1 signaling in astrocytes. Using a mouse model, we examined the role of astrocytic ephrin-B1 signaling in oligodendrocyte development by deleting ephrin-B1 specifically in astrocytes during the postnatal days (P)14-P28 period and used mRNA analysis, immunohistochemistry, and mouse behaviors to study its effects on oligodendrocytes and myelination. We found that deletion of astrocytic ephrin-B1 downregulated many genes associated with oligodendrocyte development, myelination, and lipid metabolism in the hippocampus and the corpus callosum. Additionally, we observed a reduced number of oligodendrocytes and impaired myelination in the corpus callosum of astrocyte-specific ephrin-B1 KO mice. Finally, our data show reduced motor strength in these mice exhibiting clasping phenotype and impaired performance in the rotarod test most likely due to impaired myelination. Our studies provide new evidence that astrocytic ephrin-B1 positively regulates oligodendrocyte development and myelination, potentially through astrocyte-oligodendrocyte interactions.
星形胶质细胞被认为参与少突胶质细胞的发育和髓鞘形成，然而，星形胶质细胞调节少突胶质细胞的机制尚不清楚。我们的研究结果表明，星形胶质细胞通过 Ephrin-B1 信号通路调节少突胶质细胞发育的新机制。我们使用小鼠模型，通过在 P14-P28 期间特异性敲除星形胶质细胞中的 Ephrin-B1，研究了星形胶质细胞 Ephrin-B1 信号在少突胶质细胞发育中的作用，并使用 mRNA 分析、免疫组织化学和小鼠行为来研究其对少突胶质细胞和髓鞘形成的影响。我们发现，星形胶质细胞 Ephrin-B1 的缺失下调了海马体和胼胝体中许多与少突胶质细胞发育、髓鞘形成和脂质代谢相关的基因。此外，我们观察到星形胶质细胞特异性 Ephrin-B1 KO 小鼠胼胝体中的少突胶质细胞数量减少，髓鞘形成受损。最后，我们的数据显示这些小鼠的运动力量减弱，表现出抓握表型，在旋转棒试验中的表现也受损，这很可能是由于髓鞘形成受损所致。我们的研究提供了新的证据，表明星形胶质细胞 Ephrin-B1 正向调节少突胶质细胞的发育和髓鞘形成，这可能是通过星形胶质细胞-少突胶质细胞相互作用实现的。
