Romeo Russell D, Bellani Rudy, Karatsoreos Ilia N, Chhua Nara, Vernov Mary, Conrad Cheryl D, McEwen Bruce S
Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021, USA.
Endocrinology. 2006 Apr;147(4):1664-74. doi: 10.1210/en.2005-1432. Epub 2006 Jan 12.
Both the magnitude and the duration of the hormonal stress response change dramatically during neonatal development and aging as well as with prior experience with a stressor. However, surprisingly little is known with regard to how pubertal maturation and experience with stress interact to affect hypothalamic-pituitary-adrenal axis responsiveness. Because adolescence is a period of neurodevelopmental vulnerabilities and opportunities that may be especially sensitive to stress, it is imperative to more fully understand these interactions. Thus, we examined hormonal and neural responses in prepubertal (28 d of age) and adult (77 d of age) male rats after exposure to acute (30 min) or more chronic (30 min/d for 7 d) restraint stress. We report here that after acute stress, prepubertal males exhibited a significantly prolonged hormonal stress response (e.g. ACTH and total and free corticosterone) compared with adults. In contrast, after chronic stress, prepubertal males exhibited a higher response immediately after the stressor, but a faster return to baseline, compared with adults. Additionally, we demonstrate that this differential stress reactivity is associated with differential neuronal activation in the paraventricular nucleus of the hypothalamus, as measured by FOS immunohistochemistry. Using triple-label immunofluorescence histochemistry, we found that a larger proportion of CRH, but not arginine vasopressin, cells are activated in the arginine vasopressin in response to both acute and chronic stress in prepubertal animals compared with adults. These data indicate that experience-dependent plasticity of the hypothalamic-pituitary-adrenal neuroendocrine axis is significantly influenced by pubertal maturation.
在新生儿发育、衰老过程中以及与应激源的既往经历相关时，激素应激反应的强度和持续时间都会发生显著变化。然而，令人惊讶的是，关于青春期成熟与应激经历如何相互作用以影响下丘脑 - 垂体 - 肾上腺轴反应性，我们所知甚少。由于青春期是神经发育脆弱且充满机遇的时期，可能对压力特别敏感，因此更全面地了解这些相互作用势在必行。因此，我们检测了青春期前（28日龄）和成年（77日龄）雄性大鼠在暴露于急性（30分钟）或更慢性（每天30分钟，持续7天）束缚应激后的激素和神经反应。我们在此报告，急性应激后，与成年大鼠相比，青春期前雄性大鼠的激素应激反应（如促肾上腺皮质激素、总皮质酮和游离皮质酮）显著延长。相比之下，慢性应激后，与成年大鼠相比，青春期前雄性大鼠在应激源作用后立即表现出更高的反应，但恢复到基线的速度更快。此外，我们证明这种不同的应激反应性与下丘脑室旁核中不同的神经元激活有关，通过FOS免疫组织化学测量。使用三重标记免疫荧光组织化学，我们发现与成年动物相比，青春期前动物在急性和慢性应激下，更多比例的促肾上腺皮质激素释放激素（CRH）细胞（而非精氨酸加压素细胞）在精氨酸加压素的作用下被激活。这些数据表明，下丘脑 - 垂体 - 肾上腺神经内分泌轴的经验依赖性可塑性受到青春期成熟的显著影响。
