(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.

Pediatric cardio-autonomic response to variable effort after severe traumatic brain injury

“…This is in line with previous studies on this topic [2]. A sedentary lifestyle might also be associated with sympathetic dominance [16]. It is not possible to differentiate between the effect of the primary brain insult and the secondary disability of less activity regarding the results which were presented in the study.…”

The link between exercise and titin passive stiffness

“…The impact of exercise training versus sedentary conditions on the neural control of the circulation under healthy conditions and disease states have been reviewed recently (Michelini & Stern, ; Patel & Zheng, ; Mischel et al . ).…”

“…There is growing evidence that changes in the autonomic nervous system also impact regulation of the heart and vascular system, if not the organs themselves. The impact of exercise training versus sedentary conditions on the neural control of the circulation under healthy conditions and disease states have been reviewed recently (Michelini & Stern, 2009;Patel & Zheng, 2012;Mischel et al 2015).…”

Central Glutamatergic-Purinergic System Importance in Brain/Neural Plasticity

“…In a preclinical model of neurocardiac function, exercise-induced neuroplasticity of the rostral ventrolateral medulla (RVLM) has an inhibitory effect on glutamatergic neurotransmission, which, in turn, decreases sympathetic activity. This neuroplasticity in the RVLM may represent a mechanism by which regular exercise prevents inactivity-related cardiovascular disease [18].…”