Molecular Connections Between Arousal and Metabolic Disease: Orexin and Modafinil

摘要

Metabolic diseases are known to be tightly linked to arousal-sleep cycles and impact cognitive function. Importantly, the armed forces represent a population at significant risk for increased stress and disrupted arousal-sleep cycles. Because the incidence of metabolic disease and obesity is increasing, even in these physically fit individuals, understanding the interactions between these systems is highly significant. Further, some anti-fatigue pharmacologies (e.g.,modafinil) are already used in military settings, though their long-term effects on metabolism or central nervous system function are not well-understood. We have completed Year 3 of the proposed funding period to assess the physiological and behavioral effects of this pharmacology on rat subjects and identify potential molecular mechanisms activated by nutrients. We have begun additional studies to elucidate the specific nutrients that confer these effects with an eye toward specifically identifying the source of possible beneficial consequences for stress-reduction and cognition. Additionally, we have recently observed chronic stress can differentially regulate expression of the orexin system in CNS circuits critical to complex behavior and memory processes. Finally, we have made further progress on identifying the molecular and cellular mechanisms of these systems.