Regulation of blood-brain barrier integrity by <i>Dmp1</i> -expressing astrocytes through mitochondrial transfer-Reference-Cited by-同舟云学术

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

Published:2024-06-28 Issue:26 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Liu Delin¹²³⁴^ORCID,Liao Peng³⁴^ORCID,Li Hao³⁴,Tong Sihan³⁴,Wang Bingqi³⁴,Lu Yafei³⁴,Gao Youshui³^ORCID,Huang Yigang³,Zhou Hao⁵^ORCID,Shi Linjing⁵,Papadimitriou John¹⁶,Zong Yao¹,Yuan Jun¹²^ORCID,Chen Peilin¹,Chen Ziming¹,Ding Peng³⁴^ORCID,Zheng Yongqiang⁷,Zhang Changqing³⁴^ORCID,Zheng Minghao¹²^ORCID,Gao Junjie³⁴⁷^ORCID

Affiliation:

1. Centre for Orthopaedic Research, Medical School, The University of Western Australia, Nedlands, Western Australia 6009, Australia.

2. Perron Institute for Neurological and Translational Science, Nedlands, Western Australia 6009, Australia.

3. Department of Orthopaedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.

4. Institute of Microsurgery on Extremities, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.

5. Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310009, China.

6. Department of Pathology, Pathwest, Nedlands, Western Australia 6009, Australia.

7. Department of Orthopaedics, Jinjiang Municipal Hospital, Jinjiang, Fujian Province, 362200, China.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adk2913

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