Effect of ER-beta gene disruption on estrogenic regulation of anxiety in female mice.

Effect of ER-beta gene disruption on estrogenic regulation of anxiety in female mice.
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DOI:
10.1016/j.physbeh.2008.10.014
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发表时间:
2009-02-16
影响因子:
2.9
通讯作者:
Ogawa, Sonoko
Ogawa, Sonoko
中科院分区:
医学3区
文献类型:
--
作者:
Tomihara, Kazuya;Soga, Tomoko;Nomura, Masayoshi;Korach, Kenneth S.;Gustafsson, Jan-Ake;Pfaff, Donald W.;Ogawa, Sonoko

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已有研究表明,去性腺的雌性小鼠长期服用雌激素会增加焦虑水平。另一方面,最近的一项研究报道,雌激素可能通过雌激素受体(ER)β来下调焦虑水平。在本研究中,我们研究了ER-β在雌性小鼠长期雌激素治疗后调节焦虑水平中的作用。将去性腺的ER-β基因敲除(βERKO)雌性小鼠及其野生型(βWT)仔鼠植入不同剂量(实验1:2.0μg/天,实验2:1.0、0.4、0.2或0.1μg/天)的苯甲酸雌二醇(EB)或安慰剂颗粒。实验1:明暗转换试验(LDT),实验2:明暗转换试验(LDT),高架迷宫试验(EPM)和社会调查试验(SIT)。我们发现,在较高剂量下,长期治疗EB对βWT和βErko小鼠都有引发焦虑的作用,表现为在低剂量照射期间,在光侧花费的时间和两侧之间的转换次数减少。相反,一些行为测量表明,较低剂量的EB治疗可能通过ER-β降低焦虑水平。特别是,EB在SIT中的抗焦虑作用在βWT小鼠中比在βErko小鼠中更明显。综上所述,本研究结果表明,雌激素对雌性小鼠既有抗焦虑作用,也有致焦虑作用,ER-β基因突变不影响雌激素对雌性小鼠产生焦虑的调节,但部分影响了对雌性小鼠的焦虑调节。
It has been shown that long-term estrogen treatment in gonadectomized female mice increases anxiety levels. On the other hand, a recent study has reported that estrogen may down-regulate the levels of anxiety by acting through estrogen receptor (ER) β. In the present study, we investigated the role of ER-β in the regulation of anxiety levels in female mice after long-term estrogen treatment. Gonadectomized ER-β knockout (βERKO) female mice and their wild type (βWT) littermates were implanted several different doses (experiment 1: 2.0μg/day, experiment 2: 1.0, 0.4, 0.2 or 0.1μg/day) of an estradiol benzoate (EB) or placebo pellet. Ten days after pellet implant, behavioral tests commenced to measure the anxiety levels (experiment 1: light-dark transition test (LDT), experiment 2: LDT, elevated plus maze test (EPM) and social investigation test (SIT)). We found that, at higher-doses, long-term treatment of EB had anxiogenic effects in both β WT and βERKO mice as indicated by a decrease of the time spent in the light side and the number of transitions between two sides during LDT. In contrast, several behavioral measurements indicated that the lower-doses treatment of EB might reduce the anxiety levels possibly through ER-β. Particularly, the anxiolytic effects of EB in the SIT were more pronounced in βWT mice than βERKO mice. Together, the findings in the present study suggest that estrogen may have both anxiolytic and anxiogenic effects in female mice, and that ER-β gene disruption did not affect anxiogenic regulation by estrogen in female mice, but partially affected anxiolytic regulation.
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