BDNF-related mechanisms of neuroplasticity in the rostral ventrolateral medulla of sedentary versus active rats
Authors: Haidar Sarah , Fyk-Kolodziej Bozena , Mueller Patrick 
Published: May 2023

Overactivity of the sympathetic nervous system is implicated in cardiovascular disease (CVD), the leading cause of death. Sympathetic nerve activity is regulated by a region in the brainstem, the rostral ventrolateral medulla (RVLM). The RVLM contains sympathoexcitatory neurons, which when overactive, likely contribute to hypertension, a leading risk factor for CVD. RVLM neurons undergo structural and functional neuroplasticity. Our laboratory reported that sedentary vs active conditions promote increased dendritic branching in rostral regions of the RVLM. Increased dendritic branching is consistent with previous observations of greater sympathoexcitation after activation of the RVLM in sedentary vs active rats. Regulation of dendritic branching is mediated by brain-derived neurotrophic factor (BDNF). Interestingly, the mature form (mBDNF) but not its precursor (proBDNF) is significantly elevated in rostral regions of the RVLM in sedentary rats. Since conversion of proBDNF to mBDNF is facilitated by tissue plasminogen activator (tPA), the purpose of this study was to determine whether tPA expression in the RVLM is different under sedentary vs active conditions. We hypothesized that tPA levels are higher in rostral regions of the RVLM of sedentary vs active animals. Four-week-old, male Sprague-Dawley rats were divided into two groups: Active (running wheels) or Sedentary (no running wheel) for 12 weeks (n=4 ea.). Rats were sacrificed for fresh tissue removal under deep anesthesia, and brainstems were cryosectioned serially (80 μm). Bilateral tissue punches of the RVLM were retrieved and rostrocaudal boundaries were verified by cresyl violet staining of post-punched sections. Bilateral punches were pooled for gel electrophoresis based on rostrocaudal location. Expression levels of tPA and GAPDH (loading control) were detected using fluorescent immunoblotting and acquisition on a Typhoon Laser-scanner. Band densities were quantified using ImageQuant software. Sedentary conditions resulted in significant increases in tPA/GAPDH in the most rostral RVLM region compared to the two caudal regions (p=0.0006, for both; two way ANOVA). In contrast, active conditions did not result in increases of tPA/GAPDH in rostral vs caudal regions of the RVLM (p>0.05, across all levels); appearing lower in the most rostral region compared to sedentary rats (p=0.085). Interestingly, tPA/GAPDH was significantly lower in the most caudal region of the RVLM in sedentary vs active rats (p=0.017). Our data suggests that sedentary conditions may drive increased tPA and possibly greater conversion of proBDNF to mBDNF in the rostral RVLM. However, higher tPA expression may also contribute to similar branching following active conditions in the caudal RVLM compared to sedentary rats. Thus, additional studies are necessary to clarify the role of tPA in mechanisms of neuroplasticity in RVLM neurons involved in blood pressure regulation in sedentary vs active animals. 1R01-HL161233 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.