Regulation of blood-brain barrier integrity by Dmp1-expressing astrocytes through mitochondrial transfer

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2024-06-28 DOI:10.1126/sciadv.adk2913

Delin Liu, Peng Liao, Hao Li, Sihan Tong, Bingqi Wang, Yafei Lu, Youshui Gao, Yigang Huang, Hao Zhou, Linjing Shi, John Papadimitriou, Yao Zong, Jun Yuan, Peilin Chen, Ziming Chen, Peng Ding, Yongqiang Zheng, Changqing Zhang, Minghao Zheng, Junjie Gao

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Abstract

The blood-brain barrier (BBB) acts as the crucial physical filtration structure in the central nervous system. Here, we investigate the role of a specific subset of astrocytes in the regulation of BBB integrity. We showed that Dmp1-expressing astrocytes transfer mitochondria to endothelial cells via their endfeet for maintaining BBB integrity. Deletion of the Mitofusin 2 (Mfn2) gene in Dmp1-expressing astrocytes inhibited the mitochondrial transfer and caused BBB leakage. In addition, the decrease of MFN2 in astrocytes contributes to the age-associated reduction of mitochondrial transfer efficiency and thus compromises the integrity of BBB. Together, we describe a mechanism in which astrocytes regulate BBB integrity through mitochondrial transfer. Our findings provide innnovative insights into the cellular framework that underpins the progressive breakdown of BBB associated with aging and disease.

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表达 Dmp1 的星形胶质细胞通过线粒体转移调节血脑屏障的完整性

血脑屏障（BBB）是中枢神经系统中至关重要的物理过滤结构。在这里，我们研究了特定星形胶质细胞亚群在调节血脑屏障完整性中的作用。我们发现，表达 Dmp1 的星形胶质细胞通过其内膜将线粒体转移到内皮细胞，以维持 BBB 的完整性。在表达Dmp1的星形胶质细胞中缺失Mitofusin 2（Mfn2）基因会抑制线粒体的转移并导致BBB渗漏。此外，星形胶质细胞中 MFN2 的减少导致了与年龄相关的线粒体转移效率的降低，从而损害了 BBB 的完整性。综上所述，我们描述了星形胶质细胞通过线粒体转移调节 BBB 完整性的机制。我们的发现为我们深入了解衰老和疾病相关的 BBB 逐步崩溃的细胞框架提供了创新性见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.