Fenoglio Kristina A, Brunson Kristen L, Avishai-Eliner Sarit, Chen Yuncai, Baram Tallie Z
19182 Jamboree Boulevard, University of California, Irvine, Med Sci I Room B160, Irvine, California 92697-4475, USA.
Endocrinology. 2004 Jun;145(6):2702-6. doi: 10.1210/en.2004-0111. Epub 2004 Mar 24.
Early-life experience including maternal care profoundly influences hormonal stress responses during adulthood. Daily handling on postnatal day (P) 2-9, eliciting augmented maternal care upon returning pups to their cage, permanently modifies the expression of the stress neuromodulators corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR). We have previously demonstrated reduced hypothalamic CRF expression already at the end of the handling period, followed by enhanced hippocampal GR mRNA levels (by P45). However, the initial site(s) and time of onset of these enduring changes have remained unclear. Therefore, we used semiquantitative in situ hybridization to delineate the spatiotemporal evolution of CRF and GR expression throughout stress-regulatory brain regions in handled (compared with undisturbed) pups. Enhanced CRF mRNA expression was apparent in the amygdaloid central nucleus (ACe) of handled pups already by P6. By P9, the augmented CRF mRNA levels persisted in ACe, accompanied by increased peptide expression in the bed nucleus of the stria terminalis and reduced expression in the paraventricular nucleus. The earliest change in GR consisted of reduced expression in the ACe of handled pups on P9, a time point when hippocampal GR expression was not yet affected. Thus, altered gene expression in ACe, bed nucleus of the stria terminalis as well as paraventricular nucleus may contribute to the molecular cascade by which handling (and increased maternal care) influences the stress response long term.
包括母性照料在内的早期生活经历会深刻影响成年期的激素应激反应。在出生后第（P）2 - 9天进行每日抚摸，当幼崽被放回笼中时会引发更多的母性照料，这会永久性地改变应激神经调节剂促肾上腺皮质激素释放因子（CRF）和糖皮质激素受体（GR）的表达。我们之前已经证明，在抚摸期结束时，下丘脑CRF表达就已降低，随后海马体GR mRNA水平升高（到P45时）。然而，这些持久变化的初始位点和起始时间仍不清楚。因此，我们使用半定量原位杂交来描绘在接受抚摸的（与未受干扰的相比）幼崽的整个应激调节脑区中CRF和GR表达的时空演变。到P6时，接受抚摸的幼崽杏仁体中央核（ACe）中CRF mRNA表达增强就已很明显。到P9时，ACe中CRF mRNA水平升高持续存在，同时终纹床核中的肽表达增加，室旁核中的表达减少。GR的最早变化包括在P9时接受抚摸的幼崽的ACe中表达降低，此时海马体GR表达尚未受到影响。因此，ACe、终纹床核以及室旁核中基因表达的改变可能促成了分子级联反应，通过这种级联反应，抚摸（以及增加的母性照料）长期影响应激反应。
