Mitochondria play a significant role in pathogenesis of clinical depression and their function can be impaired by inflammation and alterations in hypothalamic–pituitary–adrenal axis. Sexual context is also a relevant factor in the incidence of mood disorders, and could have a strong influence during an immune challenge. Therefore, in this study we investigated whether the effects of seven-day lipopolysaccharide (LPS) treatment on glucocorticoid receptor (GR) could be associated with apoptosis and alterations in energy metabolism in hippocampus of female and male Wistar rats with depressive-like behavior. To that end, we measured the mitochondrial levels of GR and its phosphoisoforms pGR232 and pGR246 in hippocampus of female and male rats, as well as the mRNA levels of two GR-regulated mitochondrial genes, cyclooxygenase -1 and -3 (COX-1 and -3). We also measured alterations in the extrinsic and intrinsic apoptotic pathways in mitochondria and cytosol of hippocampus of these animals, and the levels of cleaved cytosolic poly [ADP-ribose] polymerase-1 (PARP-1) protein. We discovered that even though LPS treatment induced behavioral alterations and affected corticosterone levels and apoptosis in a similar manner in both sexes, it affected mitochondrial GR differently in males and females. Namely, the treatment decreased levels of mitochondrial GR and pGR232/pGR246 ratio only in females, and these alterations were followed by decreased mRNA levels of COX-1 and COX-3 only in this sex. The alterations in COX-1 and COX-3 mRNA levels could indicate impaired oxidative metabolism and diminished mitochondrial function in hippocampus of this sex.

线粒体在临床抑郁症的发病机制中起重要作用，其功能可能因炎症和下丘脑-垂体-肾上腺轴的改变而受损。性环境也是情绪障碍发生率的一个相关因素，并且可能在免疫挑战期间产生强烈影响。因此，在本研究中，我们研究了 7 天脂多糖 (LPS) 治疗对糖皮质激素受体 (GR) 的影响是否与具有抑郁样行为的雌性和雄性 Wistar 大鼠海马的细胞凋亡和能量代谢改变有关。为此，我们测量了雌性和雄性大鼠海马中 GR 及其磷酸亚型 pGR232 和 pGR246 的线粒体水平，以及两个 GR 调节的线粒体基因环氧合酶 -1 和 -3（COX-1 和-3)。我们还测量了这些动物的线粒体和海马胞质溶胶中外在和内在凋亡途径的变化，以及裂解的胞质多聚 [ADP-核糖] 聚合酶-1 (PARP-1) 蛋白的水平。我们发现，尽管 LPS 治疗在两性中以相似的方式诱导行为改变并影响皮质酮水平和细胞凋亡，但它在男性和女性中对线粒体 GR 的影响不同。即，治疗仅在女性中降低了线粒体 GR 水平和 pGR232/pGR246 比率，并且这些改变之后仅在该性别中降低了 COX-1 和 COX-3 的 mRNA 水平。COX-1 和 COX-3 mRNA 水平的改变可能表明该性别海马中的氧化代谢受损和线粒体功能减弱。