Da Costa A P, Kampa R J, Windle R J, Ingram C D, Lightman S L
Department of Medicine, University of Bristol, Bristol Royal Infirmary, UK.
Brain Res. 1997 Oct 3;770(1-2):151-62. doi: 10.1016/s0006-8993(97)00764-6.
Central administration of corticotropin-releasing hormone (CRH) induces immediate-early gene (IEG) expression (c-fos and NGFI-B) in forebrain structures in a pattern similar to that observed following restraint stress. Lactating rats display modified neuroendocrine and behavioural responses to stress which have been hypothesized to be at least partially mediated through changes within the circuitry converging on the PVN, including CRH activated pathways. Quantitative measures of regional expression of c-fos and NGFI-B mRNA representative of two classical intracellular pathways, were used to define modification of the circuitry involved in the altered response to central CRH in the lactating female. Compared to saline controls, virgin female rats injected with 5 micrograms CRH i.c.v. displayed significantly increased immediate-early gene expression in the hypothalamic paraventricular nucleus (PVN), arcuate nucleus, lateral septum, bed nucleus of the stria terminalis, central, medial and cortical nuclei of the amygdala, and all subfields of the hippocampal formation. In lactating rats treated with CRH there was a significant increase in c-fos gene expression in the CeA and in the hippocampal subfields CA1, CA4 and dentate gyrus but not in the other areas examined. The i.c.v. administration of CRH significantly increased NGFI-B expression in the PVN, arcuate nucleus, medial amygdala and all hippocampal subfields of virgin rats. Lactating rats treated with CRH failed to show a significant increase in NGFI-B expression in the PVN, median eminence, arcuate nucleus, medial amygdala, CA2 and CA3 subfields of the hippocampus. These results further suggest that changes in specific neural circuits might at least partially underlie the modified responses to CRH and perhaps to stress in the lactating female.
中枢给予促肾上腺皮质激素释放激素(CRH)可诱导前脑结构中立即早期基因(IEG)(c-fos和NGFI-B)的表达,其模式与束缚应激后观察到的相似。哺乳期大鼠对应激的神经内分泌和行为反应有所改变,据推测这至少部分是通过汇聚于室旁核(PVN)的神经回路内的变化介导的,包括CRH激活的通路。采用代表两条经典细胞内途径的c-fos和NGFI-B mRNA区域表达的定量测量方法,来确定哺乳期雌性大鼠对中枢CRH反应改变所涉及的神经回路的变化。与生理盐水对照组相比,经脑室内注射5微克CRH的未孕雌性大鼠,其下丘脑室旁核(PVN)、弓状核、外侧隔、终纹床核、杏仁核的中央核、内侧核和皮质核以及海马结构的所有亚区中立即早期基因的表达显著增加。在用CRH处理的哺乳期大鼠中,中央杏仁核(CeA)以及海马亚区CA1、CA4和齿状回中的c-fos基因表达显著增加,但在其他检查区域中未增加。脑室内注射CRH可显著增加未孕大鼠PVN、弓状核、内侧杏仁核和所有海马亚区中NGFI-B的表达。用CRH处理的哺乳期大鼠在PVN、正中隆起、弓状核、内侧杏仁核、海马的CA2和CA3亚区中NGFI-B的表达未显示出显著增加。这些结果进一步表明,特定神经回路的变化可能至少部分是哺乳期雌性大鼠对CRH以及可能对应激反应改变的基础。