Shaw Gladys A, Wegener Amy J, Neigh Gretchen N
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA.
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA.
Physiol Behav. 2024 Dec 1;287:114681. doi: 10.1016/j.physbeh.2024.114681. Epub 2024 Aug 28.
Chronic activation of the hypothalamic-pituitary-adrenal axis increases circulating corticosterone levels, causing a host of downstream behavioral, molecular, and metabolic changes. Here, we assess the effects of chronic exogenous CORT administration on changes in behavior and mitochondrial respiration in hippocampal synaptosomes of male and female mice. Adult male (n = 15) and female (n = 17) C57Bl/6NTac mice were given 35ug/mL CORT or vehicle dissolved in their drinking water for 21 consecutive days. Chronic CORT increased piloerection in males only. Although volume of CORT-containing water consumed was similar between males and females, circulating plasma and fecal corticosterone levels were only elevated in CORT-exposed males. Behavioral effects of CORT were evident in the Y-maze such that CORT caused a decrease in direct revisits in both sexes. There was no observed presentation of anxiety-like behavior following chronic CORT administration. Functional hippocampal synaptosomes were analyzed for mitochondrial respiration using Agilent's Cell Mito Stress test. Chronic CORT caused a decrease in synaptic mitochondria basal respiration, maximal respiration, proton leak, and ATP production in both sexes. Despite only observing an effect of chronic CORT on corticosterone concentrations in fecal and blood samples of males, chronic CORT induced marked changes in hippocampal synaptic mitochondrial function of both sexes. These data highlight the importance of considering effects of stress hormone exposure on neural function even in the absence of measurable peripheral elevations in females.
下丘脑 - 垂体 - 肾上腺轴的慢性激活会增加循环中的皮质酮水平，引发一系列下游行为、分子和代谢变化。在此，我们评估慢性外源性皮质酮给药对雄性和雌性小鼠海马突触体行为变化和线粒体呼吸的影响。成年雄性（n = 15）和雌性（n = 17）C57Bl/6NTac小鼠连续21天饮用溶解有35μg/mL皮质酮或赋形剂的水。慢性皮质酮处理仅使雄性小鼠出现竖毛现象。尽管雄性和雌性小鼠饮用含皮质酮水的量相似，但仅在接受皮质酮处理的雄性小鼠中，循环血浆和粪便中的皮质酮水平升高。皮质酮的行为效应在Y迷宫实验中很明显，即皮质酮使两性的直接重访次数减少。慢性给予皮质酮后未观察到焦虑样行为表现。使用安捷伦细胞线粒体应激测试分析功能性海马突触体的线粒体呼吸。慢性皮质酮处理使两性突触线粒体的基础呼吸、最大呼吸、质子泄漏和ATP产生均减少。尽管仅在雄性小鼠的粪便和血液样本中观察到慢性皮质酮对皮质酮浓度的影响，但慢性皮质酮诱导了两性海马突触线粒体功能的显著变化。这些数据凸显了即使在雌性小鼠外周未出现可测量升高的情况下，考虑应激激素暴露对神经功能影响的重要性。
