Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions

摘要: The endothelial cells of the blood-brain barrier participate in regulation glutamate concentrations brain interstitial fluid by taking up glutamate. However, metabolism has not been characterized, nor is its role homeostasis and energy production known. aim this study was to investigate dehydrogenase (GDH) expression probe functional significance. primary were isolated from bovine mouse brains, human derived induced pluripotent stem cells. GDH on protein level function investigated model systems using western blotting, confocal microscopy, 13 C-glutamate metabolism, Seahorse assay. In study, it shown that expressed murine capillaries cultured as well human-induced cell-derived confirmed mice carrying a central nervous system-specific knockout. Endothelial all tested species metabolized α-ketoglutarate, which subsequently entered tricarboxylic acid (TCA)-cycle. Brain maintained mitochondrial oxygen consumption rates, when supplied with alone, whereas addition glucose did lead additional consumption. conclusion, directly take metabolize utilize resulting α-ketoglutarate cycle ultimately yield ATP if unavailable.