Brain Endothelial Cells Maintain Lactate Homeostasis and Control Adult Hippocampal Neurogenesis
Copyright © 2019 Elsevier Inc. All rights reserved..
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.
| Errataetall: |
CommentIn: Cell Stem Cell. 2019 Dec 5;25(6):729-731. - PMID 31809733 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Cell stem cell - 25(2019), 6 vom: 05. Dez., Seite 754-767.e9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jun [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.09.2020 Date Revised 14.09.2020 published: Print-Electronic CommentIn: Cell Stem Cell. 2019 Dec 5;25(6):729-731. - PMID 31809733 Citation Status MEDLINE |
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| doi: |
10.1016/j.stem.2019.09.009 |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Yu, Zhenyang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wenjing |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Wenliang |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Shuyue |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Xiaopeng |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yanxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Lan, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Lanqun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Huanming |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Weixiang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xiao |e verfasserin |4 aut | |
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