Couto-Moraes Renato, Palermo-Neto João, Markus Regina Pekelmann
Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, Universidade de São Paulo, Sao Paulo, Brazil.
Ann N Y Acad Sci. 2009 Feb;1153:193-202. doi: 10.1111/j.1749-6632.2008.03978.x.
The temporal organization of mammals presents a daily adjustment to the environmental light/dark cycle. The environmental light detected by the retina adjusts the central clock in the suprachiasmatic nuclei, which innervate the pineal gland through a polysynaptic pathway. During the night, this gland produces and releases the nocturnal hormone melatonin, which circulates throughout the whole body and adjusts several bodily functions according to the existence and duration of darkness. We have previously shown that during the time frame of an inflammatory response, pro-inflammatory cytokines, such as tumor necrosis factor-alpha, inhibit while anti-inflammatory mediators, such as glucocorticoids, enhance the synthesis of melatonin, interfering in the daily adjustment of the light/dark cycle. Therefore, injury disconnects the organism from environmental cycling, while recovery restores the light/dark information to the whole organism. Here, we extend these observations by evaluating the effect of a mild restraint stress, which did not induce macroscopic gastric lesions. After 2 h of restraint, there was an increase in circulating corticosterone, indicating activation of the hypothalamus-pituitary-adrenal (HPA) axis. In parallel, an increase in melatonin production was observed. Taking into account the data obtained with models of inflammation and stress, we reinforce the hypothesis that the activity of the pineal gland is modulated by the state of the immune system and the HPA axis, implicating the darkness hormone melatonin as a modulator of defense responses.
哺乳动物的时间组织呈现出对环境光/暗周期的每日调整。视网膜检测到的环境光会调整视交叉上核中的中央时钟，该时钟通过多突触途径支配松果体。在夜间，该腺体产生并释放夜间激素褪黑素，褪黑素在全身循环，并根据黑暗的存在和持续时间调整多种身体功能。我们之前已经表明，在炎症反应期间，促炎细胞因子，如肿瘤坏死因子-α，会抑制褪黑素的合成，而抗炎介质，如糖皮质激素，则会增强褪黑素的合成，从而干扰光/暗周期的每日调整。因此，损伤会使生物体与环境循环脱节，而恢复则会将光/暗信息恢复到整个生物体。在这里，我们通过评估轻度束缚应激的影响来扩展这些观察结果，这种应激并未诱导宏观胃部病变。束缚2小时后，循环皮质酮增加，表明下丘脑-垂体-肾上腺（HPA）轴被激活。同时，观察到褪黑素产生增加。考虑到从炎症和应激模型获得的数据，我们强化了这样一种假设，即松果体的活动受免疫系统和HPA轴状态的调节，这意味着黑暗激素褪黑素是防御反应的调节剂。
