title: (In)activity-related neuroplasticity in brainstem control of sympathetic outflow: unraveling underlying molecular, cellular, and anatomical mechanisms.
abstract: More people die as a result of physical inactivity than any other preventable risk factor including smoking, high cholesterol, and obesity. Cardiovascular disease, the number one cause of death in the United States, tops the list of inactivity-related diseases. Nevertheless, the vast majority of Americans continue to make lifestyle choices that are creating a rapidly growing burden of epidemic size and impact on the United States healthcare system. It is imperative that we improve our understanding of the mechanisms by which physical inactivity increases the incidence of cardiovascular disease and how exercise can prevent or rescue the inactivity phenotype. The current review summarizes research on changes in the brain that contribute to inactivity-related cardiovascular disease. Specifically, we focus on changes in the rostral ventrolateral medulla (RVLM), a critical brain region for basal and reflex control of sympathetic activity. The RVLM is implicated in elevated sympathetic outflow associated with several cardiovascular diseases including hypertension and heart failure. We hypothesize that changes in the RVLM contribute to chronic cardiovascular disease related to physical inactivity. Data obtained from our translational rodent models of chronic, voluntary exercise and inactivity suggest that functional, anatomical, and molecular neuroplasticity enhances glutamatergic neurotransmission in the RVLM of sedentary animals. Collectively, the evidence presented here suggests that changes in the RVLM resulting from sedentary conditions are deleterious and contribute to cardiovascular diseases that have an increased prevalence in sedentary individuals. The mechanisms by which these changes occur over time and their impact are important areas for future study.
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan; and.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Mischel
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan; and.
authors.forename: Madhan
authors.initials: M
authors.lastname: Subramanian
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan; and.
authors.forename: Maryetta D
authors.initials: MD
authors.lastname: Dombrowski
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan; and Cardiovascular Medicine, Physiology and Centre for Neuroscience, School of Medicine, Flinders University, Bedford Park, South Australia, Australia.
authors.forename: Ida J
authors.initials: IJ
authors.lastname: Llewellyn-Smith
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan; and pmueller@med.wayne.edu.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Mueller
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D002319:Cardiovascular System / Q000294:innervation*; D015444:Exercise; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008526:Medulla Oblongata / Q000378:metabolism / Q000503:physiopathology*; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity; D012018:Reflex; D012307:Risk Factors; D057185:Sedentary Behavior; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D009435:Synaptic Transmission; D013997:Time Factors
chemical_list: D018698:Glutamic Acid
keywords: arterial pressure; cardiovascular disease; inactivity; neurons; sympathetic nervous system