title: Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health.
abstract: Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain-derived neurotrophic factor (BDNF) plays a critical role in the integration and optimization of behavioral and metabolic responses to environments with limited energy resources and intense competition. In particular, BDNF signaling mediates adaptive responses of the central, autonomic, and peripheral nervous systems from exercise and DER. In the hypothalamus, BDNF inhibits food intake and increases energy expenditure. By promoting synaptic plasticity and neurogenesis in the hippocampus, BDNF mediates exercise- and DER-induced improvements in cognitive function and neuroprotection. DER improves cardiovascular stress adaptation by a mechanism involving enhancement of brainstem cholinergic activity. Collectively, findings reviewed in this paper provide a rationale for targeting BDNF signaling for novel therapeutic interventions in a range of metabolic and neurological disorders.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. rothmansm@mail.nih.gov
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Rothman
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Griffioen
authors.forename: Ruiqian
authors.initials: R
authors.lastname: Wan
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D031204:Caloric Restriction; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D003071:Cognition; D004435:Eating; D004734:Energy Metabolism; D015444:Exercise; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D051379:Mice; D009473:Neuronal Plasticity; D009765:Obesity
chemical_list: D019208:Brain-Derived Neurotrophic Factor