Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.
Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.
Front Endocrinol (Lausanne). 2020 Oct 7;11:570560. doi: 10.3389/fendo.2020.570560. eCollection 2020.
Aging in women is associated with low estrogen, but also with cognitive decline and affective disorders. Whether low estrogen is causally responsible for these behavioral symptoms is not clear. Thus, we aimed to examine the role of estradiol in anxiety-like behavior and memory in rats at middle age. Twelve-month old female rats underwent ovariectomy (OVX) or were treated with 1 mg/kg of letrozole-an aromatase inhibitor. In half of the OVX females, 10 μg/kg of 17β-estradiol was supplemented daily for 4 weeks. Vehicle-treated sham-operated and OVX females served as controls. For behavioral assessment open field, elevated plus maze and novel object recognition tests were performed. Interaction between ovarian condition and additional treatment had the main effect on anxiety-like behavior of rats in the open field test. In comparison to control females, OVX females entered less frequently into the center zone of the open field ( < 0.01) and showed lower novel object discrimination ( = 0.05). However, estradiol-supplemented OVX rats had higher number of center-zone entries ( < 0.01), spent more time in the center zone ( < 0.05), and showed lower thigmotaxis ( < 0.01) when compared to OVX group. None of the hormonal manipulations affected anxiety-like behavior in the elevated plus maze test significantly, but a mild effect of interaction between ovarian condition and treatment was shown ( = 0.05). In conclusion, ovariectomy had slight negative effect on open-field ambulation and short-term recognition memory in middle-aged rats. In addition, a test-specific anxiolytic effect of estradiol supplementation was found. In contrast, letrozole treatment neither affected anxiety-like behavior nor memory.
女性衰老与雌激素水平降低有关，但也与认知能力下降和情感障碍有关。雌激素是否是这些行为症状的因果关系尚不清楚。因此，我们旨在研究雌二醇在中年大鼠焦虑样行为和记忆中的作用。12 个月大的雌性大鼠接受卵巢切除术（OVX）或接受 1 毫克/千克来曲唑（一种芳香酶抑制剂）治疗。在一半的 OVX 雌性大鼠中，每天补充 10μg/kg 的 17β-雌二醇 4 周。接受载体治疗的假手术和 OVX 雌性大鼠作为对照。进行行为评估，包括旷场、高架十字迷宫和新物体识别测试。卵巢状况和额外治疗之间的相互作用对大鼠旷场测试中的焦虑样行为有主要影响。与对照雌性大鼠相比，OVX 雌性大鼠进入旷场中心区域的频率较低（<0.01），新物体辨别能力较低（=0.05）。然而，与 OVX 组相比，补充雌二醇的 OVX 大鼠进入中心区域的次数更多（<0.01），在中心区域停留的时间更长（<0.05），并且表现出较低的触壁行为（<0.01）。激素处理对高架十字迷宫测试中的焦虑样行为没有显著影响，但显示出卵巢状况和治疗之间相互作用的轻微影响（=0.05）。总之，卵巢切除术对中年大鼠旷场运动和短期识别记忆有轻微的负面影响。此外，还发现了雌二醇补充的特定抗焦虑作用。相比之下，来曲唑治疗既不影响焦虑样行为，也不影响记忆。
