Natarajan Reka, Northrop Nicole A, Yamamoto Bryan K
a Department of Neurosciences , University of Toledo College of Medicine , Toledo , OH , USA.
Stress. 2015;18(6):668-76. doi: 10.3109/10253890.2015.1087502. Epub 2015 Sep 28.
Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. The body temperature is controlled in part, by the medial preoptic area (mPOA) of the hypothalamus. To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress (CUS) paradigm produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 d of CUS. Four days after the last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10 °C were recorded. The CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that the CUS induced changes to the 5HTergic system alter mPOA function in thermoregulation. These findings help us to explain the mechanisms underlying chronic stress-induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed.
已知慢性应激会影响大脑中的血清素（5HT）神经传递并改变体温。体温部分由下丘脑的内侧视前区（mPOA）控制。为了研究慢性应激对5HT的影响以及它如何影响体温调节，我们检查了暴露于慢性不可预测应激（CUS）范式是否会通过降低5HT神经传递而导致mPOA的体温调节功能发生长期改变。成年雄性Sprague-Dawley大鼠接受了21天的CUS。在最后一次应激暴露后四天，记录其在饲养笼中的基础体温以及在保持于10°C的冷室中的体温。与无应激（NoStress）大鼠相比，CUS大鼠在13:00时的皮下基础体温显著更高。虽然NoStress大鼠在暴露于冷室30和60分钟时能够从基础水平显著升高体温，但CUS大鼠对寒冷表现出体温过低反应。在CUS期间用甲吡酮（一种皮质酮合成抑制剂）进行治疗，可阻断应激诱导的对冷刺激的体温降低反应。CUS还降低了mPOA中5HT转运蛋白的免疫反应性，并且在CUS暴露后向mPOA注射5HT2A/C激动剂会使应激大鼠对寒冷表现出敏感的体温过高反应。这些结果表明，CUS诱导的5HT能系统变化改变了mPOA在体温调节中的功能。这些发现有助于我们解释慢性应激诱导的疾病（如慢性疲劳综合征，其中观察到持久的体温调节缺陷）的潜在机制。
