MAR 16, 2017 12:00 PM PDT

The Orexin/Hypocretin System in Aging and Cognition

Presented At Neuroscience 2017
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  • Associate Professor , University of South Carolina School of Medicine
      Jim Fadel received his Ph.D. in Neuroscience from The Ohio State University and was a postdoctoral fellow at Vanderbilt University Medical Center prior to accepting a faculty position at the University of South Carolina School of Medicine in 2002. He is currently an Associate Professor in the Department of Pharmacology, Physiology and Neuroscience and directs the School's Medical Neuroscience course.
      Dr. Fadel studies the anatomical and neurochemical basis of age-related cognitive decline. His work has received continuous extramural grant support since 2000 from multiple NIH institutes as well as private foundation and industry sources. He is a member of the American Federation for Aging Research National Scientific Advisory Council and in 2012 received the USC Education Foundation Health Sciences Research Award. He has served on several NIH grant review panels and has also served on the editorial board for the journal, Neuropsychopharmacology. In addition to his primary interests in brain aging, Jim collaborates extensively on projects related to the biology of neuropsychiatric disorders, and has received Young Investigator Awards from the National Alliance for Research on Schizophrenia and Depression and the International Congress on Schizophrenia Research. Dr. Fadel has also been active in neuroscience outreach efforts with schools, community organizations and undergraduate institutions around the state.


    Alterations in homeostatic functions such as energy balance and sleep patterns are frequently seen in the elderly and these changes may precede and predict subsequent cognitive decline.  A novel hypothesis is that some of these seemingly disparate manifestations of age-related deficits may share common underlying neurobiological mechanisms; that is, brain regions that are involved in homeostasis regulate the activity of brain regions that mediate the appropriate behavioral and cognitive responses to physiological challenges, and these interactions may be impacted in aging.  The hypothalamic orexin/hypocretin neuropeptide system regulates energy balance, arousal and cognition via widespread ascending and descending projections.  We have shown in animal models that the orexin system plays an important role in modulating cognitive—particularly attentional—function and that aging is associated with dramatic reductions in the number of orexin neurons and deficits in activation of cortical and hippocampal circuitry by homeostatically-relevant stimuli.  Recent clinical literature has also shown significant loss of these neurons in age-related neurological disorders, including Alzheimer’s and Parkinson’s disease.  Here, I will review and expand on these findings and discuss the potential of the orexin system as a therapeutic target for “healthy brain aging”, with effects on both cognitive and physiological correlates of aging.

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