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

Xiaofei Gao; Xing Jun Chen; Meng Ye; Jun Liszt Li; Nannan Lu; Di Yao; Bo Ci; Fei Chen; Lijun Zheng; Yating Yi; Shiwen Zhang; Zhanying Bi; Xinwei Gao; Yuanlei Yue; Tingbo Li; Jiafu Lin; Ying Chao Shi; Kaibin Shi; Nicholas E. Propson; Yubin Huang; Katherine Poinsatte; Zhaohuan Zhang; Dale B. Bosco; Shi Bing Yang; Ralf H. Adams; Volkhard Lindner; Fen Huang; Long Jun Wu; Hui Zheng; Simon Hippenmeyer; Ann M. Stowe; Bo Peng; Marta Margeta; Qingchun Guo; Xiaoqun Wang; Qiang Liu; Jakob Körbelin; Martin Trepel; Hui Lu; Guoen Cai; Bo O. Zhou; Bo Shen; Ying Mei Lu; Wenzhi Sun; Jie Min Jia; Feng Han; Hu Zhao; Robert M. Bachoo; Woo Ping Ge

doi:10.1038/s41467-025-60308-0

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

Xiaofei Gao
, Xing Jun Chen
, Meng Ye
, Jun Liszt Li
, Nannan Lu
, Di Yao
, Bo Ci
, Fei Chen
, Lijun Zheng
, Yating Yi
, Shiwen Zhang
, Zhanying Bi
, Xinwei Gao
, Yuanlei Yue
, Tingbo Li
, Jiafu Lin
, Ying Chao Shi
, Kaibin Shi
, Nicholas E. Propson
, Yubin Huang

Katherine Poinsatte, Zhaohuan Zhang, Dale B. Bosco, Shi Bing Yang, Ralf H. Adams, Volkhard Lindner, Fen Huang, Long Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M. Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O. Zhou, Bo Shen, Ying Mei Lu, Wenzhi Sun, Jie Min Jia, Feng Han, Hu Zhao, Robert M. Bachoo, Woo Ping Ge

Producción científica: Article › revisión exhaustiva

14 Citas (Scopus)

Resumen

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.

Idioma original	English
Número de artículo	5840
Número de páginas	18
Publicación	Nature Communications
Volumen	16
N.º	1
DOI	https://doi.org/10.1038/s41467-025-60308-0
Estado	Published - dic 2025

Nota bibliográfica

Publisher Copyright:
© The Author(s) 2025.

Financiación

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, for critical reading. We acknowledge the assistance of the CIBR Imaging core. This work was supported by grants from the STI2030-Major Projects (2022ZD0204700), CAMS Innovation Fund for Medical Sciences (CIFMS, 2024-I2M-ZD-012), the National Natural Science Foundation of China (32170964), and funds from CIBR to W.G., grants from National Natural Science Foundation of China to J.M.J, (32170961), National Natural Science Foundation of China (No. 31800864), Westlake University start-up funds to J-M. J. and German Research Foundation, DFG (No. 335447717) to J.K. German Research Foundation (DFG, No 523830300) to M.T. and J.K. 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 also supported by 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.; 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.

Financiadores	Número del financiador
UT Southwestern Live Cell Imaging Facility
Westlake University
University of California San Francisco	2022ZD0204700
National Natural Science Foundation of China (NSFC)	32170964, 81473202, 31600839
CIBR	32170961, 31800864
National Institutes of Health (NIH)	RF1AG054111, R01 NS088555, R01 AG020670
National Childhood Cancer Registry – National Cancer Institute	P30 CA142543K
American the American Heart Association	81370031, 17IRG33410377
Shenzhen Technology Development Program	JCYJ20170818163320865
Chinese Academy of Medical Sciences Initiative for Innovative Medicine	2024-I2M-ZD-012
Deutsche Forschungsgemeinschaft	335447717, 523830300
H2020 European Research Council	725780
National Key Basic Research and Development Program of China	2016YFE0125400

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

Acceder al documento

10.1038/s41467-025-60308-0

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ChemiDoc Imaging System Bio-Rad
Stowe, A. (Manager), Chen, M. (Operator), Hubbard, W. (Operator), Gipson-Reichardt, C. (Operator), Sullivan, P. (Operator), Roberts, J. (Operator), Trout, A. (Operator), Whiteheart, S. (Operator) & Wood, J. (Operator)
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Gao, X., Chen, X. J., Ye, M., Li, J. L., Lu, N., Yao, D., Ci, B., Chen, F., Zheng, L., Yi, Y., Zhang, S., Bi, Z., Gao, X., Yue, Y., Li, T., Lin, J., Shi, Y. C., Shi, K., Propson, N. E., ... Ge, W. P. (2025). Reduction of neuronal activity mediated by blood-vessel regression in the adult brain. Nature Communications, 16(1), Artículo 5840. https://doi.org/10.1038/s41467-025-60308-0

@article{b24378083ecc4b248803682edad57f58,

title = "Reduction of neuronal activity mediated by blood-vessel regression in the adult brain",

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.",

author = "Xiaofei Gao and Chen, \{Xing Jun\} and Meng Ye and Li, \{Jun Liszt\} and Nannan Lu and Di Yao and Bo Ci and Fei Chen and Lijun Zheng and Yating Yi and Shiwen Zhang and Zhanying Bi and Xinwei Gao and Yuanlei Yue and Tingbo Li and Jiafu Lin and Shi, \{Ying Chao\} and Kaibin Shi and Propson, \{Nicholas E.\} and Yubin Huang and Katherine Poinsatte and Zhaohuan Zhang and Bosco, \{Dale B.\} and Yang, \{Shi Bing\} and Adams, \{Ralf H.\} and Volkhard Lindner and Fen Huang and Wu, \{Long Jun\} and Hui Zheng and Simon Hippenmeyer and Stowe, \{Ann M.\} and Bo Peng and Marta Margeta and Qingchun Guo and Xiaoqun Wang and Qiang Liu and Jakob K{\"o}rbelin and Martin Trepel and Hui Lu and Guoen Cai and Zhou, \{Bo O.\} and Bo Shen and Lu, \{Ying Mei\} and Wenzhi Sun and Jia, \{Jie Min\} and Feng Han and Hu Zhao and Bachoo, \{Robert M.\} and Ge, \{Woo Ping\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41467-025-60308-0",

language = "English",

volume = "16",

number = "1",

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Gao, X, Chen, XJ, Ye, M, Li, JL, Lu, N, Yao, D, Ci, B, Chen, F, Zheng, L, Yi, Y, Zhang, S, Bi, Z, Gao, X, Yue, Y, Li, T, Lin, J, Shi, YC, Shi, K, Propson, NE, Huang, Y, Poinsatte, K, Zhang, Z, Bosco, DB, Yang, SB, Adams, RH, Lindner, V, Huang, F, Wu, LJ, Zheng, H, Hippenmeyer, S, Stowe, AM, Peng, B, Margeta, M, Guo, Q, Wang, X, Liu, Q, Körbelin, J, Trepel, M, Lu, H, Cai, G, Zhou, BO, Shen, B, Lu, YM, Sun, W, Jia, JM, Han, F, Zhao, H, Bachoo, RM & Ge, WP 2025, 'Reduction of neuronal activity mediated by blood-vessel regression in the adult brain', Nature Communications, vol. 16, n.º 1, 5840. https://doi.org/10.1038/s41467-025-60308-0

TY - JOUR

T1 - Reduction of neuronal activity mediated by blood-vessel regression in the adult brain

AU - Gao, Xiaofei

AU - Chen, Xing Jun

AU - Ye, Meng

AU - Li, Jun Liszt

AU - Lu, Nannan

AU - Yao, Di

AU - Ci, Bo

AU - Chen, Fei

AU - Zheng, Lijun

AU - Yi, Yating

AU - Zhang, Shiwen

AU - Bi, Zhanying

AU - Gao, Xinwei

AU - Yue, Yuanlei

AU - Li, Tingbo

AU - Lin, Jiafu

AU - Shi, Ying Chao

AU - Shi, Kaibin

AU - Propson, Nicholas E.

AU - Huang, Yubin

AU - Poinsatte, Katherine

AU - Zhang, Zhaohuan

AU - Bosco, Dale B.

AU - Yang, Shi Bing

AU - Adams, Ralf H.

AU - Lindner, Volkhard

AU - Huang, Fen

AU - Wu, Long Jun

AU - Zheng, Hui

AU - Hippenmeyer, Simon

AU - Stowe, Ann M.

AU - Peng, Bo

AU - Margeta, Marta

AU - Guo, Qingchun

AU - Wang, Xiaoqun

AU - Liu, Qiang

AU - Körbelin, Jakob

AU - Trepel, Martin

AU - Lu, Hui

AU - Cai, Guoen

AU - Zhou, Bo O.

AU - Shen, Bo

AU - Lu, Ying Mei

AU - Sun, Wenzhi

AU - Jia, Jie Min

AU - Han, Feng

AU - Zhao, Hu

AU - Bachoo, Robert M.

AU - Ge, Woo Ping

PY - 2025/12

Y1 - 2025/12

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AB - 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.

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AN - SCOPUS:105009720823

SN - 2041-1723

VL - 16

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5840

ER -

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

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

Acceder al documento

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