Creatine Protects against Excitoxicity in an In Vitro Model of Neurodegeneration

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 H2O2. In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance, leading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively antagonized the H2O2-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as 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 a primary prophylactic compound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of creatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with reduced glutamate spillover, oxidative stress and subsequent excitotoxicity

Social-ecological considerations informing a universal screening strategy for sleep health in the community

“Poor sleep health” (PSH), defined as reduced amount of sleep and non-restorative sleep, affects cognitive, social and emotional development. Evidence suggests an association of sleep deprivation and mental health problems; however, there are no universal concepts allowing a first-tier screening of PSH at a community level. The focus of this narrative review is to highlight the cultural context of the current medicalized approach to PSH and to suggest social ecological strategies informing new and holistic community-based screening concepts. We present two conceptual screening frameworks; a “medical” and a merged “social emotional wellbeing framework” and combine them utilizing the concept of “ecologies.” The first framework proposes the incorporation of “sleep” in the interpretation of “vigilance” and “inappropriate” labeled behaviors. In the first framework, we provide a logic model for screening the myriad of presentations and possible root causes of sleep disturbances as a tool to assess daytime behaviors in context with PSH. In the second framework, we provide evidence that informs screening for “social emotional wellbeing” in the context of predictive factors, perpetuating factors and predispositions through different cultural perspectives. The distinct goals of both frameworks are to overcome training-biased unidirectional thinking and a priori medicalization of challenging, disruptive and/or disobedient behaviors. The latter has been explicitly informed by the critical discourse on colonization and its consequences, spearheaded by First Nations. Our “transcultural, transdisciplinary and transdiagnostic screening framework” may serve as a starting point from which adaptations of medical models could be developed to suit the purposes of holistic screening, diagnosis, and treatment of complex childhood presentations in different cultural contexts.</p