The increased incidence of depression in women going through peri-menopause suggests that fluctuations in estrogen levels may increase the risk of developing depression. Nonetheless, this psychiatric disorder is likely to be multifactorial and consequently an additional trigger may be needed to induce depression in this population. Stress could be such a trigger. We therefore investigated the effect of ovarian estrogen depletion and chronic mild stress (CMS) on depressive-like behavior and brain metabolism in female rats. Approximately 2 and 9 weeks after estrogen depletion by ovariectomy, behavioral changes were assessed in the open-field test and the forced swim test, and brain metabolism was measured with [18F]FDG PET imaging. A subset of animals was subjected to a 6-weeks CMS protocol starting 17 days after ovariectomy. Short-term estrogen depletion had a significant effect on brain metabolism in subcortical areas, but not on behavior. Differences in depressive-like behavior were only found after prolonged estrogen depletion, leading to an increased immobility time in the forced swim test. Prolonged estrogen depletion also resulted in an increase in glucose metabolism in frontal cortical areas and hippocampus, whereas a decrease glucose metabolism was found in temporal cortical areas, hypothalamus and brainstem. Neither short-term nor prolonged estrogen depletion caused anxiety-like behavior. Changes in body weight, behavior and brain glucose metabolism were not significantly affected by CMS. In conclusion, ovarian estrogen depletion resulted in changes in brain metabolism and depressive-like behavior, but these changes were not enhanced by CMS.

中文翻译：

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雌性大鼠卵巢切除引起的抑郁样行为和脑糖代谢变化不受慢性轻度应激的影响

围绝经期女性抑郁症的发病率增加表明雌激素水平的波动可能会增加患抑郁症的风险。尽管如此，这种精神疾病可能是多因素的，因此可能需要额外的触发因素来诱发该人群的抑郁症。压力可能是这样的触发因素。因此，我们研究了卵巢雌激素耗竭和慢性轻度应激 (CMS) 对雌性大鼠抑郁样行为和脑代谢的影响。在卵巢切除术导致雌激素耗竭后大约 2 周和 9 周，在开放场试验和强迫游泳试验中评估行为变化，并用 [18F]FDG PET 成像测量脑代谢。一部分动物在卵巢切除术后 17 天开始接受 6 周的 CMS 方案。短期雌激素耗竭对皮层下区域的脑代谢有显着影响，但对行为没有影响。抑郁样行为的差异仅在长期雌激素耗尽后发现，导致强迫游泳测试中的不动时间增加。长时间的雌激素消耗也导致额叶皮质区和海马体的葡萄糖代谢增加，而颞皮质区、下丘脑和脑干的葡萄糖代谢减少。短期或长期的雌激素耗竭都不会导致焦虑样行为。CMS 对体重、行为和脑葡萄糖代谢的变化没有显着影响。总之，卵巢雌激素耗竭导致大脑代谢和抑郁样行为的变化，但这些变化并没有被 CMS 增强。