Table_5_Age-related and individual features of the HPA axis stress responsiveness under constant light in nonhuman primates.xlsx

The hypothalamic-pituitary-adrenal (HPA) axis is a key adaptive neuroendocrine system, dysfunction of which plays an important role in the increasing incidence of stress-dependent age-related pathology. Among the environmental factors effecting increase age-related diseases, great importance is given to disturbances of the light-dark schedule, particularly with increased illumination at night. While disruption of the light-dark schedule has long been recognized as a powerful behavioral stressor, little is known regarding stress reactivity of the HPA under constant light (CL) conditions, especially with aging and depending on the features of stress behavior. The purpose of this investigation was to study the age-related and individual features of the HPA axis response to acute stress exposure (ASE) under chronic CL in nonhuman primates that are known to differ in behavioral responsiveness to stress. Young and old female rhesus monkeys (with control standard behavior or anxiety and depression-like behavior) were exposed to CL (24 h light/day, 330-400 lux for 4 to 8 weeks). Control young and old monkeys were exposed to standard lighting (SL) with natural light during the day and darkness at night. All animals were subjected to ASE (restriction of mobility for 2 hours), functional tests with corticotrophin-releasing hormone and arginine-vasopressin, and study of circadian rhythms of cortisol and pineal melatonin secretion. For the first time an inhibitory effect of CL on the reaction of the adrenal cortex to ASE was revealed in all individuals, regardless of age and preexisting behavior stress reactivity, the mechanisms of which were age-dependent: due to inhibition of the pituitary ACTH secretion in young animals and mainly not affecting the ACTH secretion in old individuals. There were no significant changes in melatonin secretion both in young and old animals. The observed CL inhibition of adrenal cortical reactivity to ASE may be useful to correct increased vulnerability to ASE observed in individuals with preexisting anxiety and depression-like stress behaviors. On the other hand, the CL induced decrease in adrenal stress reactivity of behaviorally normal animals suggests a potential risk of reducing the adaptive capacity of the organism under conditions of continuous light exposure.

下丘脑-垂体-肾上腺轴（hypothalamic-pituitary-adrenal, HPA）是关键的适应性神经内分泌系统，其功能异常与应激相关年龄相关性病理发生率的升高密切相关。在导致年龄相关性疾病发生率上升的各类环境因素中，明暗节律紊乱（尤其是夜间光照增强）受到广泛关注。尽管明暗节律紊乱早已被证实为强效行为应激源，但目前对于持续光照（constant light, CL）条件下HPA轴的应激反应性，尤其是随衰老进程变化以及与应激行为特征相关的调控机制，仍知之甚少。本研究旨在针对应激行为反应性存在固有差异的非人类灵长类动物，探究慢性持续光照环境下，HPA轴对急性应激暴露（acute stress exposure, ASE）的年龄相关与个体特征差异。实验选取年轻与老年雌性恒河猴，分为行为表现正常组与焦虑、抑郁样行为组，给予持续光照处理（每日24小时光照，光照强度330~400 lux，持续4~8周）；对照组年轻与老年恒河猴则采用标准光照（standard lighting, SL）环境，即日间自然光照射、夜间黑暗环境。所有受试动物均接受急性应激暴露（2小时运动限制）、促肾上腺皮质激素释放激素与精氨酸加压素功能试验，并检测皮质醇与松果体褪黑素分泌的昼夜节律。本研究首次发现，无论年龄与基线应激行为反应性如何，持续光照均可抑制所有个体的肾上腺皮质对应激暴露的反应，且该抑制效应存在年龄依赖性：年轻动物表现为垂体促肾上腺皮质激素（adrenocorticotropic hormone, ACTH）分泌受抑制，而老年动物则主要不受ACTH分泌变化的影响。年轻与老年动物的褪黑素分泌均未出现显著变化。本研究观察到的持续光照对肾上腺皮质应激反应的抑制效应，或可用于改善既往存在焦虑、抑郁样行为个体的急性应激暴露易感性升高问题。另一方面，持续光照诱导行为正常动物的肾上腺应激反应性降低，提示持续光照暴露可能会降低机体的适应性调节能力，存在潜在健康风险。