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Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis.

Cell stem cell (2019-11-26)
Jun Wang, Yaxiong Cui, Zhenyang Yu, Wenjing Wang, Xuan Cheng, Wenliang Ji, Shuyue Guo, Qing Zhou, Ning Wu, Yan Chen, Ying Chen, Xiaopeng Song, Hui Jiang, Yanxiao Wang, Yu Lan, Bin Zhou, Lanqun Mao, Jin Li, Huanming Yang, Weixiang Guo, Xiao Yang
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tamoxifen, ≥99%
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Retinoic acid, ≥98% (HPLC), powder
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Donkey serum
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5-Bromo-2′-deoxyuridine, ≥99% (HPLC)
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Forskolin, from Coleus forskohlii, ≥98% (HPLC), powder
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Evans Blue, Dye content ≥75 %
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Anti-NeuN Antibody, clone A60, clone A60, Chemicon®, from mouse
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Lactate Assay Kit, sufficient for 100 colorimetric or fluorometric tests
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Sodium L-lactate, ≥99.0% (NT)
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Glucose Colorimetric/Fluorometric Assay Kit, sufficient for 100 colorimetric or fluorometric tests
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5-Bromo-2′-deoxyuridine, BioUltra, ≥99%