Cell Stem Cell
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.
| 论文编号: | DOI:10.1016/j.stem.2019.09.009 |
| 论文题目: | Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis |
| 英文论文题目: | Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis |
| 第一作者: | Jun Wang, Yaxiong Cui, Zhenyang Yu, Wenjing Wang, Xuan Cheng, Wenliang Ji, Shuyue Guo, Qing Zhou Ning Wu5, Yan Chen, Ying Chen, Xiaopeng Song, Hui Jiang, Yanxiao Wang, Yu Lan, Bin Zhou, Lanqun Mao, Jin Li, Huanming Yang, Weixiang Guo & Xiao Yang |
| 英文第一作者: | Jun Wang, Yaxiong Cui, Zhenyang Yu, Wenjing Wang, Xuan Cheng, Wenliang Ji, Shuyue Guo, Qing Zhou Ning Wu5, Yan Chen, Ying Chen, Xiaopeng Song, Hui Jiang, Yanxiao Wang, Yu Lan, Bin Zhou, Lanqun Mao, Jin Li, Huanming Yang, Weixiang Guo & Xiao Yang |
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| 发表年度: | 2019-12-04 |
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| 摘要: | 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. |
| 英文摘要: | 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. |
| 刊物名称: | Cell Stem Cell |
| 英文刊物名称: | Cell Stem Cell |
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| 其它备注: | Jun Wang, Yaxiong Cui, Zhenyang Yu, Wenjing Wang, Xuan Cheng, Wenliang Ji, Shuyue Guo, Qing Zhou Ning Wu5, Yan Chen, Ying Chen, Xiaopeng Song, Hui Jiang, Yanxiao Wang, Yu Lan, Bin Zhou, Lanqun Mao, Jin Li, Huanming Yang, Weixiang Guo & Xiao Yang. Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis. Cell Stem Cell. DOI:10.1016/j.stem.2019.09.009 |
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