Smith M A, Kim S Y, van Oers H J, Levine S
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Endocrinology. 1997 Nov;138(11):4622-8. doi: 10.1210/endo.138.11.5529.
The hypothalamic-pituitary-adrenal (HPA) axis is normally quiescent during the stress-hyporesponsive period (SHRP) from day 4-14 in infant rats. However, maternal deprivation (DEP) can disinhibit the HPA axis, thus enabling neonatal rats to respond to mild stressors. In an effort to understand how DEP may alter HPA axis sensitivity, we used in situ hybridization to measure changes in the expression of stress-responsive genes in the brains of neonatal rats. Despite the minimal HPA axis response in nondeprived rats during the SHRP (postnatal day 12), the mild stress of a saline injection significantly increased messenger RNA levels of two immediate-early genes (IEGs), c-fos and NGFI-B, in the hypothalamic paraventricular nucleus (PVN) and in the cerebral cortex. Following 24 h of DEP, the induction of IEGs in response to stress was greatly potentiated in the PVN of P12 neonates. In contrast, DEP attenuated the effects of stress on IEG induction in rats that had matured beyond the SHRP (P20). Surprisingly, DEP decreased basal levels of CRH messenger RNA in the PVN at P12 and P20. Thus the SHRP most accurately refers to HPA axis insensitivity to stress because the brain itself readily responds to stress as evidenced by the induction of IEGs.
在幼鼠出生后第4至14天的应激低反应期（SHRP），下丘脑 - 垂体 - 肾上腺（HPA）轴通常处于静止状态。然而，母体剥夺（DEP）可解除对HPA轴的抑制，从而使新生大鼠能够对轻度应激源作出反应。为了了解DEP如何改变HPA轴的敏感性，我们采用原位杂交技术来测量新生大鼠大脑中应激反应基因表达的变化。尽管在SHRP期间（出生后第12天）未受剥夺的大鼠HPA轴反应极小，但盐水注射引起的轻度应激显著增加了下丘脑室旁核（PVN）和大脑皮质中两个即刻早期基因（IEGs）——c-fos和NGFI-B的信使核糖核酸水平。在24小时的DEP后，P12新生大鼠PVN中对应激的IEGs诱导作用大大增强。相比之下，DEP减弱了应激对超过SHRP期成熟大鼠（P20）IEGs诱导的影响。令人惊讶的是，DEP降低了P12和P20时PVN中促肾上腺皮质激素释放激素（CRH）信使核糖核酸的基础水平。因此，SHRP最准确地指的是HPA轴对应激不敏感，因为大脑本身很容易对应激作出反应，这由IEGs的诱导所证明。
