creatine protects against excitoxicity in an in vitro model of neurodegeneration肌酸可防止excitoxicity神经退化的体外模型.pdfVIP

Creatine Protects against Excitoxicity in an In Vitro Model of Neurodegeneration 1 1 2 ¨ ¨ 1 2 Just Genius , Johanna Geiger , Andreas Bender , Hans-Jurgen Moller , Thomas Klopstock , Dan Rujescu1* 1 Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany, 2 Department of Neurology, Ludwig-Maximilians-University, Munich, Germany Abstract Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common molecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions. Moreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents, mainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly neuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with glutamate or H O . In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance, 2 2 leading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively antagonized the H O -induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as 2 2 an antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response, which initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that high- dose creatine supplementation as a health-promoting agent in specific pathological situations or as