Presympathetic neurons in the paraventricular nucleus of the hypothalamus (PVN) play a key role in cardiovascular regulation. We have previously shown that brain-derived neurotrophic factor (BDNF), acting in the PVN, increases sympathetic activity and blood pressure and serves as a key regulator of stress-induced hypertensive responses. BDNF is known to alter glutamatergic and GABA-ergic signaling broadly in the central nervous system, but whether BDNF has similar actions in the PVN remains to be investigated. Here, we tested the hypothesis that increased BDNF expression in the PVN elevates blood pressure by enhancing NMDA receptor (NMDAR)- and inhibiting GABA_A receptor (GABA_AR)-mediated signaling. Sprague Dawley rats received bilateral PVN injections of AAV2 viral vectors expressing GFP or BDNF. Three weeks later, cardiovascular responses to PVN injections of NMDAR and GABA_AR agonists and antagonists were recorded under α-chloralose-urethane anesthesia. Additionally, expressions of excitatory and inhibitory signaling components in the PVN were assessed using immunofluorescence. Our results showed that NMDAR inhibition led to a greater decrease in blood pressure in the BDNF vs GFP group, while GABA_AR inhibition led to greater increases in blood pressure in the GFP group compared to BDNF. Conversely, GABA_AR activation decreased blood pressure significantly more in GFP vs BDNF rats. In addition, immunoreactivity of NMDAR1 was upregulated, while GABA_AR-a1 and K⁺/Cl^- cotransporter 2 were downregulated by BDNF overexpression in the PVN. In summary, our findings indicate that hypertensive actions of BDNF within the PVN are mediated, at least in part, by augmented NMDAR and reduced GABA_AR signaling.

中文翻译：

---

BDNF改变下丘脑室旁核的兴奋-抑制平衡以提高血压

下丘脑室旁核（PVN）中的前交感神经元在心血管调节中起关键作用。我们之前已经表明，脑源性神经营养因子 (BDNF) 在 PVN 中起作用，可增加交感神经活动和血压，并作为压力诱导的高血压反应的关键调节因子。已知 BDNF 在中枢神经系统中广泛改变谷氨酸和 GABA 能信号，但 BDNF 在 PVN 中是否具有类似作用仍有待研究。在这里，我们检验了 PVN 中 BDNF 表达增加通过增强 NMDA 受体 (NMDAR) 和抑制 GABA _A受体 (GABA _AR) 介导的信号传导。Sprague Dawley 大鼠接受双侧 PVN 注射表达 GFP 或 BDNF 的 AAV2 病毒载体。三周后，在 α-氯醛糖-氨基甲酸乙酯麻醉下记录了对 PVN 注射 NMDAR 和 GABA _{A R 激动剂和拮抗剂的心血管反应。}此外，使用免疫荧光评估 PVN 中兴奋性和抑制性信号成分的表达。我们的研究结果表明，与 BDNF 相比，NMDAR 抑制导致 BDNF 组的血压下降幅度更大，而 GABA _A R 抑制导致 GFP 组的血压升高幅度更大。相反，GABA _A在 GFP 与 BDNF 大鼠中，R 激活显着降低了血压。此外，NMDAR1 的免疫反应性被上调，而 GABA _A R-a1 和 K ⁺ /Cl ^-协同转运蛋白 2 被 PVN 中的 BDNF 过表达下调。总之，我们的研究结果表明，PVN 内 BDNF 的高血压作用至少部分是由增强的 NMDAR 和减少的 GABA _A R 信号介导的。