Interdisciplinary Program in Physiology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Veterinary Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
Behav Brain Res. 2022 Aug 26;432:113985. doi: 10.1016/j.bbr.2022.113985. Epub 2022 Jul 3.
Stress is associated with cardiovascular diseases. One possible mechanism is the reduction in gamma-aminobutyric acid (GABA)ergic transmission at the paraventricular nucleus (PVN), which contributes to the disinhibition of sympathoexcitatory circuits and activates sympathetic outflow. At present, the mechanism of chronic mild stress (CMS) on GABAergic transmission at the PVN and cardiac autonomic activity is not yet fully clarified. Therefore, this study was designed to investigate the effects of CMS on the GABAergic system at the PVN and on the cardiac autonomic activity. Adult male Sprague-Dawley rats were randomly assigned to control (left undisturbed in their home cage) or CMS (subjected to various mild stressors for 4 weeks). Cardiac autonomic activities were determined by heart rate variability (HRV) analysis, and GABAergic alterations at the PVN were determined from GABA levels and mRNA expression of GABA-related activities. Results showed that the CMS group had decreased HRV as determined by the standard deviation of all R-R intervals (SDNN). The low frequency (LF) and high frequency (HF) powers of the CMS group were higher than those of the control. Hence, the LF/HF ratio was consequently unaffected. These findings indicated that despite the increase in sympathetic and parasympathetic activities, the autonomic balance was preserved at 4 weeks post CMS. For the GABAergic-related parameters, the CMS group had decreased mRNA expression of glutamic acid decarboxylase-65 (GAD-65), the GABA-synthesizing enzyme, and increased mRNA expression of gamma-aminobutyric acid transporter-1 (GAT-1). Moreover, the GAD-65 mRNA expression was negatively correlated with LF. In conclusion, 4-week CMS exposure in male rats could attenuate GABAergic transmission at the PVN and alter cardiac autonomic activities.
压力与心血管疾病有关。一种可能的机制是室旁核（PVN）中γ-氨基丁酸（GABA）能传递减少，这导致交感兴奋回路去抑制，并激活交感传出。目前，慢性轻度应激（CMS）对 PVN 中的 GABA 能传递和心脏自主活动的机制尚不完全清楚。因此，本研究旨在探讨 CMS 对 PVN 中 GABA 能系统和心脏自主活动的影响。成年雄性 Sprague-Dawley 大鼠被随机分配到对照组（在其巢箱中不受干扰）或 CMS 组（接受各种轻度应激 4 周）。通过心率变异性（HRV）分析来确定心脏自主活动，通过 GABA 水平和 GABA 相关活性的 mRNA 表达来确定 PVN 中的 GABA 变化。结果表明，CMS 组的所有 R-R 间隔标准差（SDNN）降低，表明 HRV 降低。CMS 组的低频（LF）和高频（HF）功率高于对照组。因此，LF/HF 比值不受影响。这些发现表明，尽管交感和副交感活动增加，但在 CMS 后 4 周，自主平衡得以维持。对于 GABA 相关参数，CMS 组谷氨酸脱羧酶-65（GAD-65）的 mRNA 表达降低，GAD-65 是 GABA 合成酶，GABA 转运蛋白-1（GAT-1）的 mRNA 表达增加。此外，GAD-65 mRNA 表达与 LF 呈负相关。总之，4 周 CMS 暴露可减弱雄性大鼠 PVN 中的 GABA 能传递，并改变心脏自主活动。
