2. Academic Validation
  3. Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis

Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis

  • Cell Stem Cell. 2019 Dec 5;25(6):754-767.e9. doi: 10.1016/j.stem.2019.09.009.
Jun Wang 1,  Yaxiong Cui 1,  Zhenyang Yu 1,  Wenjing Wang 2,  Xuan Cheng 1,  Wenliang Ji 3,  Shuyue Guo 3,  Qing Zhou 2,  Ning Wu 4,  Yan Chen 2,  Ying Chen 4,  Xiaopeng Song 1,  Hui Jiang 2,  Yanxiao Wang 1,  Yu Lan 1,  Bin Zhou 5,  Lanqun Mao 3,  Jin Li 4,  Huanming Yang 6,  Weixiang Guo 7,  Xiao Yang 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
  • 2 BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank-Shenzhen, BGI-Shenzhen, Shenzhen 518083, China.
  • 3 Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
  • 4 Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • 5 The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, China.
  • 6 BGI-Shenzhen, Shenzhen 518083, China; James D. Watson Institute of Genome Sciences, Hangzhou 310058, China. Electronic address: [email protected].
  • 7 State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing 100101, China. Electronic address: [email protected].
  • 8 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address: [email protected].
PMID: 31761722 DOI: 10.1016/j.stem.2019.09.009
Abstract

Increased understanding of the functions of lactate has suggested a close relationship between lactate homeostasis and normal brain activity because of its importance as an energy source and signaling molecule. Here we show that lactate levels affect adult hippocampal neurogenesis. Cerebrovascular-specific deletion of PTEN causes learning and memory deficits and disrupts adult neurogenesis with accompanying lactate accumulation. Consistently, administering lactate to wild-type Animals impairs adult hippocampal neurogenesis. The endothelial PTEN/Akt pathway increases monocarboxylic acid transporter 1 (MCT1) expression to enhance lactate transport across the brain endothelium. Moreover, cerebrovascular overexpression of MCT1 or deletion of Akt1 restores MCT1 expression, decreases lactate levels, and normalizes hippocampal neurogenesis and cognitive function in PTEN mutant mice. Together, these findings delineate how the brain endothelium maintains lactate homeostasis and contributes to adult hippocampal neurogenesis and cognitive functions.

Keywords

CRISPR-Cas9; PTEN/Akt signaling; adult neurogenesis; cerebrovascular endothelial cell; cognition; lactate; monocarboxylic acid transporter 1.

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