Reduction of neuronal activity mediated by blood-vessel regression in the brain
Gao X, Li J-L, Chen X, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J-M, Yi Y, Zhang S, Shi Y-C, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco DB, Lu Y, Yang S, Adams RH, Lindner V, Huang F, Wu L-J, Zheng H, Han F, Hippenmeyer S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Körbelin J, Trepel M, Lu H, Zhou BO, Zhao H, Su W, Bachoo RM, Ge W. 2025. Reduction of neuronal activity mediated by blood-vessel regression in the brain. Nature Communications. 16, 5840.
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Author
Gao, Xiaofei;
Li, Jun-Liszt;
Chen, Xingjun;
Ci, Bo;
Chen, Fei;
Lu, Nannan;
Shen, Bo;
Zheng, Lijun;
Jia, Jie-Min;
Yi, Yating;
Zhang, Shiwen;
Shi, Ying-Chao
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All
Department
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.
Publishing Year
Date Published
2025-07-01
Journal Title
Nature Communications
Publisher
Springer Nature
Acknowledgement
The project was initiated in the Jan lab at UCSF. We thank Lily Jan and Yuh-Nung Jan’s generous support. We thank Liqun Luo’s lab for providing MADM-7 mice and Rolf A Brekken for VEGF-antibodies. Drs. Yuanquan Song (UPenn), Zhaozhu Hu (JHU), Ji Hu (ShanghaiTech), Yang Xiang (U. Mass), Hao Wang (Zhejiang U.) and Ruikang Wang (U. Washington) for critical input, colleagues at Children’s Research Institute, Departments of Neuroscience, Neurology and Neurotherapeutics, Pediatrics from UT Southwestern, and colleagues from the Jan lab for discussion. Dr. Bridget Samuels, Sean Morrison (UT Southwestern), and Nannan Lu (Zhejiang U.) for critical reading. We acknowledge the assistance of the CIBR Imaging core. We also thank UT Southwestern Live Cell Imaging Facility, a Shared Resource of the Harold C. Simmons Cancer Center, supported in part by an NCI Cancer Center Support Grant, P30 CA142543K. This work is supported by CIBR funds and the American Heart Association AWRP Summer 2016 Innovative Research Grant (17IRG33410377) to W-P.G.; National Natural Science Foundation of China (No.81370031) to Z.Z.;National Key Research and Development Program of China (2016YFE0125400)to F.H.;National Natural Science Foundations of China (No. 81473202) to Y.L.; National Natural Science Foundation of China (No.31600839) and Shenzhen Science and Technology Research Program (JCYJ20170818163320865) to B.P.; National Natural Science Foundation of China (No. 31800864) and Westlake University start-up funds to J-M. J. NIH R01NS088627 to W.L.J.; NIH: R01 AG020670 and RF1AG054111 to H.Z.; R01 NS088555 to A.M.S., and European Research Council No.725780 to S.H.;W-P.G. was a recipient of Bugher-American Heart Association Dan Adams Thinking Outside the Box Award.
Volume
16
Article Number
5840
eISSN
IST-REx-ID
Cite this
Gao X, Li J-L, Chen X, et al. Reduction of neuronal activity mediated by blood-vessel regression in the brain. Nature Communications. 2025;16. doi:10.1038/s41467-025-60308-0
Gao, X., Li, J.-L., Chen, X., Ci, B., Chen, F., Lu, N., … Ge, W. (2025). Reduction of neuronal activity mediated by blood-vessel regression in the brain. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-025-60308-0
Gao, Xiaofei, Jun-Liszt Li, Xingjun Chen, Bo Ci, Fei Chen, Nannan Lu, Bo Shen, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” Nature Communications. Springer Nature, 2025. https://doi.org/10.1038/s41467-025-60308-0.
X. Gao et al., “Reduction of neuronal activity mediated by blood-vessel regression in the brain,” Nature Communications, vol. 16. Springer Nature, 2025.
Gao X, Li J-L, Chen X, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J-M, Yi Y, Zhang S, Shi Y-C, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco DB, Lu Y, Yang S, Adams RH, Lindner V, Huang F, Wu L-J, Zheng H, Han F, Hippenmeyer S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Körbelin J, Trepel M, Lu H, Zhou BO, Zhao H, Su W, Bachoo RM, Ge W. 2025. Reduction of neuronal activity mediated by blood-vessel regression in the brain. Nature Communications. 16, 5840.
Gao, Xiaofei, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression in the Brain.” Nature Communications, vol. 16, 5840, Springer Nature, 2025, doi:10.1038/s41467-025-60308-0.
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