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Abstract
A sedentary lifestyle is the top preventable cause of death and accounts for substantial socioeconomic costs to society. The rostral ventrolateral medulla regulates blood pressure under normal and pathophysiological states, and demonstrates inactivity-related structural and functional neuroplasticity, which is subregionally specific. The purpose of this study was to examine pro- and mature forms of brain-derived neurotrophic factor (BDNF) and their respective receptors in the male rat rostral ventrolateral medulla (RVLM) and its rostral extension following sedentary vs. active (running wheels) conditions (10–12weeks). We used subregionally specific Western blotting to determine that the mature form of BDNF and its ratio to its pro-form were lower in more caudal subregions of the rostral ventrolateral medulla of sedentary rats but higher in the rostral extension when both were compared to active rats. The full-length form of the tropomyosin receptor kinase B receptor and the non-glycosylated form of the 75 kilodalton neurotrophin receptor were lower in sedentary compared to active rats. The rostrocaudal patterns of expression of the mature form of BDNF and the full-length form of the tropomyosin receptor kinase B receptor were remarkably similar to the subregionally specific patterns of enhanced dendritic branching, neuronal activity, and glutamate-mediated increases in sympathetic nerve activity observed in previous studies performed in sedentary rats. Our studies suggest signaling pathways related to BDNF within subregions of both the rostral ventrolateral medulla and its rostral extension contribute to cardiovascular disease and premature death related to a sedentary lifestyle.
Highlights
Hypertension is a major public health concern in the U.S and globally
The purpose of our study was to determine expression levels of pro form of BDNF (proBDNF) and mature form of BDNF (mBDNF) and receptors involved in their signaling pathways in different subregions of the rostral ventrolateral medulla (RVLM) and RVLMRE of sedentary compared to physically active rats
The purpose of our study was to determine expression levels of proteins involved in proBDNF and mBDNF signaling pathways in different subregions of the RVLM/RVLMRE of sedentary compared to physically active rats
Summary
Hypertension is a major public health concern in the U.S and globally. Approximately 70 million adults in the United States have hypertension, which is a significant risk factor for stroke, heart failure, and kidney failure (Kearney et al, 2005; Lloyd-Jones et al, 2009). An ever-increasing amount of evidence suggests that risk factors for hypertension, such as a lack of regular exercise, are associated with increased excitability of RVLM neurons (Martins-Pinge et al, 2005; Mischel et al, 2015; Subramanian and Mueller, 2016; Mueller et al, 2017). RVLM neurons from sedentary vs physically active rats demonstrate various forms of structural neuroplasticity, including increased dendritic branching (Mischel et al, 2014) and alterations in inhibitory and excitatory neurotransmitter receptors (Mueller et al, 2020; Fyk-Kolodziej et al, 2021), each suggestive of greater synaptic input and enhanced sympathoexcitatory and sympathoinhibitory responses following sedentary vs physically active conditions.
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