Bundzikova-Osacka Jana, Ghosal Sriparna, Packard Benjamin A, Ulrich-Lai Yvonne M, Herman James P
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Metabolic Diseases Institute , Cincinnati, OH , USA and.
Stress. 2015;18(2):221-32. doi: 10.3109/10253890.2015.1013531. Epub 2015 Mar 13.
Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic (NA) neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. In this study, we tested the hypothesis that NTS NA A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n = 5; HPA study, n = 5] or vehicle [cardiovascular study, n = 6; HPA study, n = 4]. Rats were exposed to acute restraint stress followed by 14 d of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low-frequency to high-frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress.
慢性应激会导致下丘脑 - 垂体 - 肾上腺（HPA）轴功能亢进和心血管系统内稳态失调。孤束核（NTS）中的去甲肾上腺素能（NA）神经元被认为在这些变化中起作用。在本研究中，我们检验了以下假设：NTS的NA A2神经元是心血管系统和HPA轴对急性和慢性应激反应所必需的。成年雄性大鼠接受双侧向NTS微量注射6 - 羟基多巴胺（6 - OHDA）以损毁A2神经元[心血管研究，n = 5；HPA研究，n = 5]或注射溶剂[心血管研究，n = 6；HPA研究，n = 4]。大鼠先暴露于急性束缚应激，随后接受14天的慢性可变应激（CVS）。在测试的最后一天，将大鼠置于新型高架十字迷宫（EPM）中以测试CVS后的应激反应。NTS A2神经元的损毁降低了对急性束缚的心动过速反应，证实A2神经元在急性应激后促进交感神经激活。此外，CVS增加了心率变异性的低频与高频功率之比，表明交感 - 迷走失衡，而这种效应被6 - OHDA损毁显著减弱。NTS A2神经元的损毁降低了急性束缚诱导的皮质酮分泌，但不影响对EPM的皮质酮反应，表明A2神经元促进急性HPA轴反应，但不参与CVS介导的HPA轴致敏。总体而言，这些数据表明A2神经元促进心血管系统和HPA轴对急性应激的反应。此外，A2儿茶酚胺能神经元可能导致慢性应激后交感神经驱动的潜在有害增强。
