Role of Ovarian Hormones on proBDNF Levels in the Rostral Ventrolateral Medulla: Influences Related to Neuronal Plasticity and Sympathetic Control of Blood Pressure

Abstract

Introduction: Rates of cardiovascular disease (CVD) are lower in females of reproductive age when compared to age-matched males. However, at the onset of menopause, a period characterized by decreases in ovarian hormones, there is a marked and dramatic rise in the incidence of CVD in females. Therefore, the presence of ovarian hormones may serve a cardioprotective role due to actions on several target organs, including the brain. In the brainstem, the rostral ventrolateral medulla (RVLM) has been implicated in CVD due to its direct impact on blood pressure. The RVLM also contains receptors for both the pro- and mature forms of brain-derived neurotrophic factor (proBDNF and mBDNF), a key neurotrophin which has been linked to ovarian hormones by the existence of an estrogen response element (ERE) on the bdnf gene. While mBDNF positively influences neuroplasticity by increasing connectivity between neurons (i.e., increased dendritic branching). Alternatively, proBDNF can decrease neuronal excitability—and potentially reduce RVLM overactivity—via structural actions which oppose those enacted by mBDNF. Ovarian hormones may modulate neuronal activity in the RVLM via ERE-mediated effects on proBDNF expression, providing a mechanism for the “cardioprotective” effects observed in females of reproductive age. Hypothesis: We hypothesized that the presence of ovarian hormones maintains proBDNF levels in the RVLM, minimizing activation of the RVLM, thus conferring cardioprotection. Methods: Four-week-old female Sprague-Dawley rats received ovariectomy (OVX) or sham surgery (n=5 and n=4, respectively). Rats were sacrificed at 16 weeks of age and the hindbrain was cut into 80μm coronal sections, from which the RVLM was isolated by tissue punches. Using the caudal pole of the facial nucelus as a landmark, punches were pooled into 4 discrete rostrocaudal subregions. Western blotting was performed to determine proBDNF levels in the RVLM relative to the loading control GAPDH. Results: Average proBDNF expression appeared higher in the RVLM of sham versus OVX females at all rostrocaudal levels; however, this difference did not reach statistical significance (p=0.169, main effect), perhaps due to lower sample sizes. There were no significant rostrocaudal variations in proBDNF expression (p=0.598, main effect), nor was there a significant interaction between main effects (p=0.687). Conclusions: These results suggest that the presence of ovarian hormones may maintain proBDNF expression in the RVLM; however, greater sample sizes will likely provide more definitive conclusions. Additionally, future studies could also address potential sex differences by examining the influence of ovarian hormones on expression of mBDNF. We anticipate our studies will illuminate the relationship between ovarian hormones and cardioprotection via the RVLM, thus providing insight into sex differences in CVD. R01-HL161233, APS and WSU Summer Undergraduate Research Fellowships. This is the full abstract presented at the American Physiology Summit 2024 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.