Exercise Regulates the Lactate Receptor HCAR1 and ERK1/2-PI3K/Akt Pathways to Promote Cerebral Angiogenesis

Background: We aimed to explore the ole and mechanism of lactate receptor (HCAR1) in the angiogenesis of leptomeningeal fibroblast-like cells. Methods: Human brain fibroblast-like cells were selected and some cells were deactivated, analyzed and compared with HCAR1 mRNA and protein expressions in deactivated/normal cells. HCAR1-/- mice and wild type (WT) mice were selected and divided into WT, WT exercise, HCAE1 KO and HCAE1 KO exercise groups, with 10 mice for each group. HCAR1mRNA and expression levels of proteins in fibroblast-like cells, mRNA and expression levels of proteins in Collagen IV, phosphatidylinositol trihydroxykinase (PI3K), serine threonine kinase (AKT) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) in hippocampus were compared, and the microvessel density (MVD) and diameter were calculated. Results: mRNA and expression levels of proteins in Collagen IV, PI3K, AKT, ERK1/2 and MVD in hippocampus were significantly higher in the WT exercise group than those in the WT group, microvessel diameter was significantly lower than that in the WT group (P<0.05). mRNA and expression levels of proteins in Collagen IV, PI3K, AKT, ERK1/2 and MVD in hippocampus in the HCAR1 KO and HCAR1 KO exercise groups were significantly lower than those in the WT group, microvessel diameter was higher than that in the WT group (P<0.05). Compared with the HCAR1 KO exercise group, the changes of mRNA in Collagen IV, PI3K, AKT, ERK1/2 and microvascular were not significant. Conclusion: Exercise can promote cerebral angiogenesis through the activation of the lactate receptor HCAR1 and the ERK1/2-PI3K/Akt signaling pathways.