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.

对乳酸功能的日益了解表明，由于乳酸作为能量来源和信号分子的重要性，因此乳酸稳态与大脑的正常活动之间存在着密切的关系。在这里，我们显示乳酸水平影响成年海马神经发生。脑血管特异性PTEN的缺失会导致学习和记忆障碍，并伴随着乳酸的积累破坏成人的神经发生。一致地，对野生型动物施用乳酸会损害成年海马神经发生。内皮PTEN / Akt途径增加了单羧酸转运蛋白1（MCT1）的表达，从而增强了乳酸跨脑内皮的转运。此外，MCT1的脑血管过表达或Akt1的缺失可恢复MCT1的表达，降低乳酸水平，并使PTEN突变小鼠的海马神经发生和认知功能正常化。这些发现共同说明了脑内皮如何维持乳酸稳态，并有助于成年海马神经发生和认知功能。