It is found that brain blood vessels maintain lactate homeostasis and regulate neurogenesis and cognition

Lactate has long been considered as a harmful end product of metabolism However, recent studies have shown that lactate can be used as an important energy substrate and signal molecule to affect the function of nerve cells, suggesting that brain lactate homeostasis may be essential for the stable operation of the central nervous system The hippocampal area of mammalian brain can produce new neurons through adult neurogenesis, and participate in learning and memory, emotion regulation and other functions How lactate affects neurogenesis in the hippocampus is still poorly understood As an important microenvironment of neural stem cells, cerebrovascular cells secrete cytokines, which affect the self-renewal and differentiation of neural stem cells However, it is still unclear whether cerebrovascular endothelial cells participate in the regulation of lactate homeostasis Guo Weixiang research group, Institute of genetics and developmental biology, Chinese Academy of Sciences, Institute of life group, Institute of military medicine, proteome According to the research of Yang Xiao, a national key laboratory, and Yang Huanming, a team of Huada gene, we found that lactate level in mammalian brain affects adult neurogenesis, and revealed a new mechanism of cerebrovascular regulation of adult neurogenesis by maintaining lactate homeostasis PTEN gene knockout of cerebral vascular endothelial cells leads to the over proliferation and differentiation of adult neural stem cells in the hippocampus, and the ability of learning and memory in the hippocampus is significantly reduced, accompanied by a significant increase in the concentration of lactate in the brain, while lactate injection in the hippocampus can simulate the phenotype of PTEN knockout mice Furthermore, through RNA sequencing of the cerebral vascular endothelial cells, we found that MCT1 was highly expressed in the cerebral vascular endothelial cells and negatively regulated by PI3K / Akt signaling pathway MCT1 transports lactate from central nervous system into peripheral blood to maintain lactate homeostasis in brain Furthermore, MCT1 gene knockout mice were established, and the important physiological function of MCT1 to maintain lactate homeostasis in brain was confirmed in vivo for the first time In addition, overexpression of MCT1 in cvec or AKT1 gene knockout in cvec can improve the level of lactate in brain of PTEN knockout mice, save their adult neurogenesis disorder and restore their hippocampal dependent learning and memory ability This study is the first to reveal the important physiological functions and new mechanisms of cerebral blood vessels to maintain the brain lactate homeostasis, regulate adult neurogenesis and cognitive function, and provide a new model of PTEN / Akt signal pathway up regulating MCT1 and excessive lactate transport into peripheral blood The results were published online on cell stem cell on November 21 (DOI: 10.1016/j.stem 2019.09.009) The title of the article is brain exclusive cells maintain place homeostasis to control adult hippocampal neurogenesis Researcher Yang Xiao, Guo Weixiang and academician Yang Huanming of the Chinese Academy of sciences are the corresponding authors of the paper The research was supported by the key R & D program of the Ministry of science and technology, the National Natural Science Foundation of China and the youth thousand talents program of the central organization department.