Identification of chronic stress-activated regions reveals a potential recruited circuit in rat brain.
Identification of chronic stress-activated regions reveals a potential recruited circuit in rat brain.
复制标题
DOI：
10.1111/j.1460-9568.2012.08161.x
复制
发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Herman JP
中科院分区：
文献类型：
--
作者：
Flak JN;Solomon MB;Jankord R;Krause EG;Herman JP
慢性应激诱导下丘脑室旁核（PVN）突触前和突触后改变，这与增强的兴奋性下丘脑-垂体-肾上腺皮质（HPA）轴驱动一致。介导这些分子修饰的大脑区域尚不清楚。我们假设慢性可变应激（CVS）强直激活与PVN相互作用的应激兴奋区，最终导致应激促进。为了识别慢性激活的大脑区域，ΔFosB，一个记录的强直神经元激活的标记物，在已知的应激调节边缘和脑干部位进行了评估。四个实验组包括：CVS、重复约束（RR） （HPA习惯化对照组）、与CVS动物体重匹配（WM）（体重增加减少导致循环代谢因子变化的对照组）和未处理对照组。CVS而非RR或WM诱导肾上腺肥大，表明持续的HPA轴驱动仅发生在CVS组。CVS（而不是RR或WM）选择性地增加了孤立束核、下丘脑后核以及内侧前额叶皮层边缘下和边缘前区FosB/ΔFosB核的数量，表明这些区域参与了HPA轴的慢性驱动。在RR和CVS之后，在其他区域（如下丘脑背内侧）观察到FosB/ΔFosB-immunoreactive细胞的增加，这表明在适应和非适应应激条件下都有激活。这些数据表明，不可预测的压力会独特地激活相互连接的皮层、下丘脑和脑干核，潜在地揭示了介导脑应激效应系统慢性驱动的招募电路的存在。
Chronic stress induces pre-synaptic and post-synaptic modifications in the paraventricular nucleus of the hypothalamus (PVN) that are consistent with enhanced excitatory hypothalamo-pituitary-adrenocortical (HPA) axis drive. The brain regions mediating these molecular modifications are not known. We hypothesized that chronic variable stress (CVS) tonically activates stress-excitatory regions that interact with the PVN, culminating in stress facilitation. In order to identify chronically activated brain regions, ΔFosB, a documented marker of tonic neuronal activation, was assessed in known stress regulatory limbic and brainstem sites. Four experimental groups were included: CVS, repeated restraint (RR) (control for HPA habituation), animals weight-matched (WM) to CVS animals (control for changes in circulating metabolic factors due to reduced weight gain), and non-handled controls. CVS, but not RR or WM, induced adrenal hypertrophy, indicating that sustained HPA axis drive only occurred in the CVS group. CVS (but not RR or WM) selectively increased the number of FosB/ΔFosB nuclei in the nucleus of the solitary tract, posterior hypothalamic nucleus, and both the infralimbic and prelimbic divisions of the medial prefrontal cortex, indicating an involvement of these regions in chronic drive of the HPA axis. Increases in FosB/ΔFosB-immunoreactive cells were observed following both RR and CVS in the other regions (e.g., the dorsomedial hypothalamus), suggesting activation by both habituating and non-habituating stress conditions. The data suggest that unpredictable stress uniquely activates interconnected cortical, hypothalamic, and brainstem nuclei, potentially revealing the existence of a recruited circuitry mediating chronic drive of brain stress effector systems.