Reduction of neuronal activity mediated by blood-vessel regression in the adult brain

Xiaofei Gao, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Xing-Jun Chen, Chinese Institute for Brain Research, Beijing, Beijing, 102206, China.
Meng Ye, Chinese Institute for Brain Research, Beijing, Beijing, 102206, China.
Jun-Liszt Li, Chinese Institute for Brain Research, Beijing, Beijing, 102206, China.
Nannan Lu, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Di Yao, Chinese Institute for Brain Research, Beijing, Beijing, 102206, China.
Bo Ci, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Fei Chen, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Lijun Zheng, Chinese Institute for Brain Research, Beijing, Beijing, 102206, China.
Yating Yi, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Shiwen Zhang, State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Zhanying Bi, Chinese Institute for Brain Research, Beijing, Beijing, 102206, China.
Xinwei Gao, Chinese Institute for Brain Research, Beijing, Beijing, 102206, China.
Yuanlei Yue, GW Institute for Neuroscience, the George Washington University, Washington, DC, 20037, USA.
Tingbo Li, Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Westlake Laboratory of Life Sciences and Biomedicine, School of Life Sciences, Westlake University, Hangzhou, 310024, China.
Jiafu Lin, Department of Medical College, Fujian Health College, Fuzhou, 350101, China.
Ying-Chao Shi, Guangdong Institute of Intelligence Science and Technology, Guangdong, 519031, China.
Kaibin Shi, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; Chinese Institutes for Medical Research, Beijing, 100069, China.
Nicholas E. Propson, Huffington Center on Aging, Baylor College of Medicine, Houston, TX, 77030, USA.
Yubin Huang, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Katherine Poinsatte, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX75390, USA.
Zhaohuan Zhang, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Dale B. Bosco, Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
Shi-Bing Yang, Departments of Physiology, Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA, 94158, USA.
Ralf H. Adams, Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, and Faculty of Medicine, University of Münster, D-, 48149, Münster, Germany.
Volkhard Lindner, Center for Molecular Medicine, MaineHealth Institute for Research, Scarborough, ME04074, USA.
Fen Huang, Departments of Physiology, Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA, 94158, USA.
Long-Jun Wu, Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
Hui Zheng, Huffington Center on Aging, Baylor College of Medicine, Houston, TX, 77030, USA.
Simon Hippenmeyer, Institute of Science and Technology Austria, Am Campus 1, 3400, Klosterneuburg, Austria.
Ann M. Stowe, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX75390, USA.
Bo Peng, Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, 200040, China.

Document Type

Journal Article

Publication Date

7-1-2025

Journal

Nature communications

Volume

16

Issue

1

DOI

10.1038/s41467-025-60308-0

Abstract

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and glutamate production. Our results elucidate the mechanism of vessel regression and its role in neuronal function in the adult brain.

Department

Pharmacology and Physiology

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