Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common\r\nmolecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions.\r\nMoreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents,\r\nmainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly\r\nneuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with\r\nglutamate or H2O2. In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance,\r\nleading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively\r\nantagonized the H2O2-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as\r\nan antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response,\r\nwhich initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that highdose\r\ncreatine supplementation as a health-promoting agent in specific pathological situations or as a primary prophylactic\r\ncompound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of\r\ncreatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with\r\nreduced glutamate spillover, oxidative stress and subsequent excitotoxicity.
Loading....