Schmidt M V, Levine S, Alam S, Harbich D, Sterlemann V, Ganea K, de Kloet E R, Holsboer F, Müller M B
Max Planck Institute of Psychiatry, Munich, Germany.
J Neuroendocrinol. 2006 Nov;18(11):865-74. doi: 10.1111/j.1365-2826.2006.01482.x.
The postnatal development of the mouse is characterised by a period of hypo-responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to moderate stressors. Maternal separation disinhibits this blockade of the HPA axis, but the mechanism responsible is not clear. The present study examined the influence of metabolic signals on the central and peripheral components of the HPA axis in neonatal mice aged 8 days in absence or presence of the mother. Reductions in plasma glucose and leptin as well as rapid increases in plasma ghrelin were apparent in the neonate 4 h following maternal deprivation and maximal at 8 h. In addition, maternal separation induced an increase of neuropeptide Y (NPY) mRNA expression in the arcuate nucleus, a decrease of corticotrophin-releasing hormone (CRH) mRNA expression in the paraventricular nucleus and a rise in serum corticosterone. Pharmacological manipulation of the metabolic signals attenuated the HPA response to maternal separation. Thus, the rise in plasma corticosterone induced by maternal separation was ameliorated by prevention of reduction in blood glucose or blockade of the ghrelin signalling pathway, as were the hypothalamic changes in NPY and CRH mRNAs. By contrast, leptin treatment did not affect the HPA axis response to maternal separation. Together these results suggest that metabolic signals play an important role in triggering the HPA response of the neonate to maternal separation.
小鼠出生后的发育特点是下丘脑 - 垂体 - 肾上腺（HPA）轴对中等强度应激源的反应性较低。母婴分离可解除HPA轴的这种抑制状态，但其作用机制尚不清楚。本研究在有或无母体存在的情况下，检测了代谢信号对8日龄新生小鼠HPA轴中枢和外周组成部分的影响。母体剥夺后4小时，新生小鼠血浆葡萄糖和瘦素水平降低，血浆胃饥饿素迅速升高，并在8小时达到峰值。此外，母婴分离诱导弓状核中神经肽Y（NPY）mRNA表达增加、室旁核中促肾上腺皮质激素释放激素（CRH）mRNA表达减少以及血清皮质酮水平升高。对代谢信号进行药理学调控可减弱HPA轴对母婴分离的反应。因此，通过预防血糖降低或阻断胃饥饿素信号通路，可改善母婴分离诱导的血浆皮质酮升高，同时也可改善下丘脑NPY和CRH mRNA的变化。相比之下，瘦素治疗并不影响HPA轴对母婴分离的反应。这些结果共同表明，代谢信号在触发新生小鼠HPA轴对母婴分离的反应中起重要作用。
