Abrahám I M, Kovács K J
Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Budapest, Szigony u. 43, 1083, Hungary.
Eur J Neurosci. 2000 Aug;12(8):3003-14. doi: 10.1046/j.1460-9568.2000.00176.x.
Postnatal handling, as a crucial early life experience, plays an essential role in the development of hypothalamo-pituitary-adrenal axis responses to stress. The impact of postnatal handling on the reactivity of stress-related neuronal circuitries was investigated in animals that were handled for the first 21 days of life and as adults they were exposed to physical (ether) or emotional (restraint) challenge. To assess neuronal activation we relied on the induction of immediate-early gene product c-Fos and analysed its spatial and temporal distribution at various time intervals after stress. Ether and restraint commonly activated parvocellular neurons in the hypothalamic paraventricular nucleus, and resulted in activation of brain areas providing stress-related information to the hypothalamic effector neurons and/or in regions governing autonomic and behavioural responses to stress. Beyond these areas, the strength and timing of c-Fos induction showed stressor specificity in olfactory and septal region, basal ganglia, hypothalamus, hippocampal formation, amygdala and brainstem. Handled rats displayed a lower number of c-Fos-positive cell nuclei and weaker staining intensity than non-handled controls in the hypothalamic paraventricular nucleus, bed nucleus of stria terminalis, central nucleus of amygdala, hippocampus, piriform cortex and posterior division of the cingulum. Significant differences were revealed in timing of c-Fos induction as a function of stressor and early life experience. Together, these data provide functional anatomical evidence that environmental enrichment in the early postnatal period attenuates the reactivity of stress-related neuronal circuitries in the adult rat brain.
产后护理作为一种至关重要的早期生活经历，在下丘脑 - 垂体 - 肾上腺轴对应激反应的发育中起着重要作用。在出生后前21天接受护理的动物中，研究了产后护理对应激相关神经回路反应性的影响，成年后将它们暴露于物理（乙醚）或情绪（束缚）挑战中。为了评估神经元激活，我们依赖于立即早期基因产物c-Fos的诱导，并分析了应激后不同时间间隔其空间和时间分布。乙醚和束缚通常激活下丘脑室旁核中的小细胞神经元，并导致向丘脑效应神经元提供应激相关信息的脑区激活和/或对应激的自主和行为反应进行调控的区域激活。除了这些区域，c-Fos诱导的强度和时间在嗅觉和隔区、基底神经节、下丘脑、海马结构、杏仁核和脑干中表现出应激源特异性。与未接受护理的对照组相比，接受护理的大鼠在下丘脑室旁核、终纹床核、杏仁核中央核、海马、梨状皮质和扣带回后部分中，c-Fos阳性细胞核数量较少且染色强度较弱。根据应激源和早期生活经历，c-Fos诱导的时间存在显著差异。总之，这些数据提供了功能解剖学证据，表明出生后早期的环境丰富化会减弱成年大鼠脑中应激相关神经回路的反应性。
