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Selective activation of estrogen receptors α and β: Implications for depressive-like phenotypes in female mice exposed to chronic unpredictable stress.
Hormones and Behavior ( IF 3.5 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.yhbeh.2019.104651 Rand S Eid 1 , Stephanie E Lieblich 2 , Paula Duarte-Guterman 2 , Jessica A Chaiton 2 , Amanda G Mah 3 , Sarah J Wong 2 , Yanhua Wen 2 , Liisa A M Galea 4
Hormones and Behavior ( IF 3.5 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.yhbeh.2019.104651 Rand S Eid 1 , Stephanie E Lieblich 2 , Paula Duarte-Guterman 2 , Jessica A Chaiton 2 , Amanda G Mah 3 , Sarah J Wong 2 , Yanhua Wen 2 , Liisa A M Galea 4
Affiliation
The estrogen receptor (ER) mechanisms by which 17β-estradiol influences depressive-like behaviour have primarily been investigated acutely and not within an animal model of depression. Therefore, the current study aimed to dissect the contribution of ERα and ERβ to the effects of 17β-estradiol under non-stress and chronic stress conditions. Ovariectomized (OVX) or sham-operated mice were treated chronically (47 days) with 17β-estradiol (E2), the ERβ agonist diarylpropionitrile (DPN), the ERα agonist propylpyrazole-triol (PPT), or vehicle. On day 15 of treatment, mice from each group were assigned to chronic unpredictable stress (CUS; 28 days) or non-CUS conditions. Mice were assessed for anxiety- and depressive-like behaviour and hypothalamic-pituitary-adrenal (HPA) axis function. Cytokine and chemokine levels, and postsynaptic density protein 95 were measured in the hippocampus and frontal cortex, and adult hippocampal neurogenesis was assessed. Overall, the effects of CUS were more robust that those of estrogenic treatments, as seen by increased immobility in the tail suspension test (TST), reduced PSD-95 expression, reduced neurogenesis in the ventral hippocampus, and HPA axis negative feedback dysregulation. However, we also observe CUS-dependent and -independent effects of ovarian status and estrogenic treatments. The effects of CUS on PSD-95 expression, the cytokine milieu, and in TST were largely driven by PPT and DPN, indicating that these treatments were not protective. Independent of CUS, estradiol increased neurogenesis in the dorsal hippocampus, blunted the corticosterone response to an acute stressor, and increased anxiety-like behaviour. These findings provide insights into the complexities of estrogen signaling in modulating depressive-like phenotypes under non-stress and chronic stress conditions.
中文翻译:
雌激素受体 α 和 β 的选择性激活:对暴露于慢性不可预测压力的雌性小鼠抑郁样表型的影响。
主要研究了 17β-雌二醇影响抑郁样行为的雌激素受体 (ER) 机制,而不是在抑郁症动物模型中进行研究。因此,目前的研究旨在剖析 ERα 和 ERβ 在非压力和慢性压力条件下对 17β-雌二醇的影响的贡献。卵巢切除 (OVX) 或假手术小鼠用 17β-雌二醇 (E2)、ERβ 激动剂二芳基丙腈 (DPN)、ERα 激动剂丙吡唑三醇 (PPT) 或载体长期治疗(47 天)。在治疗的第 15 天,每组的小鼠被分配到慢性不可预测的压力(CUS;28 天)或非 CUS 条件下。评估小鼠的焦虑和抑郁样行为以及下丘脑-垂体-肾上腺 (HPA) 轴功能。细胞因子和趋化因子水平,在海马和额叶皮层中测量突触后密度蛋白 95,并评估成人海马神经发生。总体而言,CUS 的效果比雌激素治疗的效果更强大,如悬尾试验 (TST) 中不动性增加、PSD-95 表达降低、腹侧海马神经发生减少和 HPA 轴负反馈失调所见。然而,我们还观察到卵巢状态和雌激素治疗的 CUS 依赖性和非依赖性影响。CUS 对 PSD-95 表达、细胞因子环境和 TST 的影响主要由 PPT 和 DPN 驱动,表明这些治疗没有保护作用。独立于 CUS,雌二醇增加了背侧海马的神经发生,减弱了皮质酮对急性压力源的反应,并增加了焦虑样行为。
更新日期:2019-12-07
中文翻译:
雌激素受体 α 和 β 的选择性激活:对暴露于慢性不可预测压力的雌性小鼠抑郁样表型的影响。
主要研究了 17β-雌二醇影响抑郁样行为的雌激素受体 (ER) 机制,而不是在抑郁症动物模型中进行研究。因此,目前的研究旨在剖析 ERα 和 ERβ 在非压力和慢性压力条件下对 17β-雌二醇的影响的贡献。卵巢切除 (OVX) 或假手术小鼠用 17β-雌二醇 (E2)、ERβ 激动剂二芳基丙腈 (DPN)、ERα 激动剂丙吡唑三醇 (PPT) 或载体长期治疗(47 天)。在治疗的第 15 天,每组的小鼠被分配到慢性不可预测的压力(CUS;28 天)或非 CUS 条件下。评估小鼠的焦虑和抑郁样行为以及下丘脑-垂体-肾上腺 (HPA) 轴功能。细胞因子和趋化因子水平,在海马和额叶皮层中测量突触后密度蛋白 95,并评估成人海马神经发生。总体而言,CUS 的效果比雌激素治疗的效果更强大,如悬尾试验 (TST) 中不动性增加、PSD-95 表达降低、腹侧海马神经发生减少和 HPA 轴负反馈失调所见。然而,我们还观察到卵巢状态和雌激素治疗的 CUS 依赖性和非依赖性影响。CUS 对 PSD-95 表达、细胞因子环境和 TST 的影响主要由 PPT 和 DPN 驱动,表明这些治疗没有保护作用。独立于 CUS,雌二醇增加了背侧海马的神经发生,减弱了皮质酮对急性压力源的反应,并增加了焦虑样行为。