Department of Biomedical Sciences and School of Biomedical Engineering, Colorado State University, Fort Collins, CO 80523, USA.
Physiol Behav. 2011 Aug 3;104(2):327-33. doi: 10.1016/j.physbeh.2011.01.003. Epub 2011 Jan 12.
The paraventricular nucleus of the hypothalamus (PVN) is a major regulator of stress responses via release of corticotropin releasing hormone (CRH) to the pituitary gland. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is characteristic of individuals with major depressive disorder (MDD). Postmortem data from individuals diagnosed with MDD show increased levels of CRH mRNA and CRH immunoreactive neurons in the PVN. In the current study, an immunohistochemical (IHC) analysis revealed increased levels of CRH in the PVN of newborn mice lacking functional GABA(B) receptors. There was no difference in the total number of CRH immunoreactive cells. By contrast, there was a significant increase in the amount of CRH immunoreactivity per cell. Interestingly, this increase in CRH levels in the GABA(B) receptor R1 subunit knockout was limited to the rostral PVN. While GABAergic regulation of the HPA axis has been previously reported in adult animals, this study provides evidence of region-specific GABA modulation of immunoreactive CRH in newborns.
下丘脑室旁核（PVN）通过释放促肾上腺皮质激素释放激素（CRH）到垂体来调节应激反应，是主要的调节者。下丘脑-垂体-肾上腺（HPA）轴的失调是重度抑郁症（MDD）患者的特征。从被诊断患有 MDD 的个体的尸检数据中显示，PVN 中的 CRH mRNA 和 CRH 免疫反应性神经元水平增加。在当前的研究中，免疫组织化学（IHC）分析显示，缺乏功能性 GABA（B）受体的新生小鼠的 PVN 中 CRH 水平升高。CRH 免疫反应性细胞的总数没有差异。相比之下，每个细胞的 CRH 免疫反应性显著增加。有趣的是，这种 GABA（B）受体 R1 亚基敲除小鼠的 CRH 水平升高仅限于 PVN 的前侧。虽然之前已经报道了 GABA 对 HPA 轴的调节作用，但这项研究提供了证据表明 GABA 对新生儿免疫反应性 CRH 的调节具有区域特异性。
