Abstract:
Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder, and there is an association between it and the development of cardiovascular disease. The aim of this study was to explore whether there is a glutamatergic pathway connecting the medial habenula (MHb) with the rostral ventrolateral medulla (RVLM) that is involved in the regulation of cardiovascular function in a rat model of PTSD. Vesicular glutamate transporter 2 (VGLUT2)-positive neurons in the MHb region were retrogradely labeled with FluoroGold (FG) by the double-labeling technique of VGLUT2 immunofluorescence and FG retrograde tracing. Rats belonging to the PTSD model group were microinjected with artificial cerebrospinal fluid (ACSF) or kynurenic acid (KYN; a nonselective glutamate receptor blocker) into their RVLM. Subsequently, with electrical stimulation of MHb, the discharge frequency of the RVLM neurons, heart rate, and blood pressure were found to be significantly increased after microinjection of ACSF using an in vivo multichannel synchronous recording technology; however, this effect was inhibited by injection of KYN. The expression of N-methyl-D-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits was significantly increased in RVLM of PTSD model rats analyzed by the Western blotting technique. These findings suggest that there may be a glutamatergic pathway connection between MHb and RVLM and that this pathway may be involved in the regulation of cardiovascular function in the PTSD model rats, by acting on NMDA and AMPA receptors in the RVLM.
摘要:
创伤后应激障碍(PTSD)是一种严重的精神疾病,它与心血管疾病的发展之间存在关联。这项研究的目的是探讨在PTSD大鼠模型中,是否存在连接内侧hu(MHb)和延髓腹外侧(RVLM)的谷氨酸能通路,该通路参与心血管功能的调节。通过VGLUT2免疫荧光和FG逆行追踪的双标记技术,用FluoroGold(FG)逆行标记MHb区域的囊泡谷氨酸转运体2(VGLUT2)阳性神经元。将属于PTSD模型组的大鼠显微注射人工脑脊液(ACSF)或犬尿酸(KYN;非选择性谷氨酸受体阻滞剂)到其RVLM中。随后,通过MHb的电刺激,RVLM神经元的放电频率,心率,并且发现使用体内多通道同步记录技术显微注射ACSF后血压显着升高;但是,注射KYN抑制了这种作用。通过Westernblotting技术分析,PTSD模型大鼠RVLM中N-甲基-D-天冬氨酸(NMDA)和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体亚基的表达显着增加。这些发现表明,MHb和RVLM之间可能存在谷氨酸通路连接,并且该通路可能参与PTSD模型大鼠心血管功能的调节。通过作用于RVLM中的NMDA和AMPA受体。