Pham Laurie, Baker Madelyn R, Shahanoor Ziasmin, Romeo Russell D
Department of Psychology and Neuroscience and Behavior Program, Barnard College of Columbia University, New York, NY 10027, United States.
Department of Psychology and Neuroscience and Behavior Program, Barnard College of Columbia University, New York, NY 10027, United States.
Brain Res. 2017 Jul 1;1666:11-16. doi: 10.1016/j.brainres.2017.04.012. Epub 2017 Apr 22.
During adolescence, the increased susceptibility to stress-related dysfunctions (e.g., anxiety, drug use, obesity) may be influenced by changes in the hormonal stress response mediated by the hypothalamic-pituitary-adrenal (HPA) axis. We have previously reported that restraint stress leads to significantly prolonged HPA responses in pre-adolescent compared to adult rats. Further, pre-adolescent animals exposed to restraint show greater levels of neural activation than adults in the paraventricular nucleus of the hypothalamus (PVN), a key nucleus integrating information from brain regions that coordinate HPA responses. Here, we examined the potential contribution of the noradrenergic A2 region of the nucleus of the solitary tract (NST) as a contributor to these age-dependent shifts in HPA reactivity. Specifically, we used double-labeled immunohistochemistry for FOS and dopamine-β-hydroxylase (DβH) to measure cellular activation and noradrenergic cells, respectively, before or after restraint stress in pre-adolescent (30days old) and adult (70days old) male rats. We also measured the density of DβH-immunoreactive fibers in the PVN as an index of noradrenergic inputs to this area. We found that pre-adolescent animals have a greater number of DβH-positive cells in the A2 region compared to adults, yet the number and percentage of double-labeled DβH/FOS cells were similar between these two ages. We found no differences between the ages in the staining intensity of DβH-immunoreactive fibers in the PVN. These data indicate there are adolescent-related changes in the number of noradrenergic cells in the A2 region, but no clear association between the increased stress reactivity prior to pubertal maturation and activation of A2 noradrenergic afferents to the PVN.
在青春期，对与压力相关的功能障碍（如焦虑、药物使用、肥胖）易感性增加，可能受到下丘脑 - 垂体 - 肾上腺（HPA）轴介导的激素应激反应变化的影响。我们之前报道过，与成年大鼠相比，束缚应激会导致青春期前大鼠的HPA反应显著延长。此外，暴露于束缚应激的青春期前动物在下丘脑室旁核（PVN）中显示出比成年动物更高水平的神经激活，PVN是整合来自协调HPA反应的脑区信息的关键核团。在这里，我们研究了孤束核（NST）的去甲肾上腺素能A2区域对这些HPA反应性年龄依赖性变化的潜在贡献。具体而言，我们使用FOS和多巴胺-β-羟化酶（DβH）的双重免疫组织化学分别测量青春期前（30日龄）和成年（70日龄）雄性大鼠在束缚应激前后的细胞激活和去甲肾上腺素能细胞。我们还测量了PVN中DβH免疫反应性纤维的密度，作为该区域去甲肾上腺素能输入的指标。我们发现，与成年动物相比，青春期前动物的A2区域中DβH阳性细胞数量更多，但这两个年龄段之间双重标记的DβH/FOS细胞数量和百分比相似。我们发现PVN中DβH免疫反应性纤维的染色强度在不同年龄之间没有差异。这些数据表明，A2区域去甲肾上腺素能细胞数量存在与青春期相关的变化，但青春期前成熟前应激反应性增加与PVN的A2去甲肾上腺素能传入激活之间没有明确关联。
