Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands; Research School of Behavioural and Cognitive Neurosciences (BCN), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Psychoneuroendocrinology. 2020 May;115:104610. doi: 10.1016/j.psyneuen.2020.104610. Epub 2020 Feb 14.
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 [F]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.
围绝经期女性抑郁发病率升高表明，雌激素水平波动可能增加抑郁发病风险。然而，这种精神障碍很可能是多因素的，因此可能需要额外的诱因才能在该人群中引发抑郁。压力可能就是这样的一个诱因。因此，我们研究了卵巢去势导致的雌激素耗竭和慢性轻度应激（CMS）对雌性大鼠抑郁样行为和大脑代谢的影响。去势大约 2 周和 9 周后，通过旷场试验和强迫游泳试验评估行为变化，并通过 [F]FDG PET 成像测量大脑代谢。一组动物在去势后 17 天开始接受为期 6 周的 CMS 方案。短期雌激素耗竭对皮质下区域的大脑代谢有显著影响，但对行为没有影响。只有在长期雌激素耗竭后才会发现抑郁样行为的差异，导致强迫游泳试验中不动时间增加。长期雌激素耗竭还导致额叶皮质区和海马体的葡萄糖代谢增加，而颞叶皮质区、下丘脑和脑干的葡萄糖代谢减少。短期和长期雌激素耗竭均不会导致焦虑样行为。体重、行为和大脑葡萄糖代谢的变化不受 CMS 的显著影响。总之，卵巢雌激素耗竭导致大脑代谢和抑郁样行为发生变化，但 CMS 并未增强这些变化。
