Estrogen Receptor-A in Medial Preoptic Area Contributes to Sex Difference of Mice in Response to Sevoflurane Anesthesia.

Estrogen Receptor-A in Medial Preoptic Area Contributes to Sex Difference of Mice in Response to Sevoflurane Anesthesia.
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内侧视前区的雌激素受体 - A导致小鼠对七氟醚麻醉的反应存在性别差异。

DOI:
10.1007/s12264-022-00825-w
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发表时间:
2022-07
影响因子:
5.6
通讯作者:
Dong, Hailong
Dong, Hailong
中科院分区:
医学2区
文献类型:
--
作者:
Zhang, Yunyun;Li, Huiming;Zhang, Xinxin;Wang, Sa;Wang, Dan;Wang, Jiajia;Tong, Tingting;Zhang, Zhen;Yang, Qianzi;Dong, Hailong

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越来越多的研究已经确定了在全身麻醉反应方面的性别差异;然而,潜在的神经机制尚不清楚。内侧视前区(MPA)是一种重要的性别二态性结构,也是调节意识转换的关键枢纽,富含雌激素受体α(ERα),特别是在参与调节睡眠的神经元簇中。我们发现雄性小鼠对七氟烷更为敏感。对内侧视前区的ERα进行药理抑制消除了七氟烷麻醉中的性别差异,尤其是延长了雄性小鼠的诱导时间并促进其苏醒,但对雌性小鼠没有影响。体外抑制ERα可抑制雄性小鼠内侧视前区的γ-氨基丁酸能和谷氨酸能神经元,但对雌性小鼠无此作用。此外,在雄性小鼠内侧视前区的γ-氨基丁酸能神经元中敲低ERα足以消除七氟烷麻醉期间的性别差异。总体而言,内侧视前区的ERα正向调节雄性小鼠内侧视前区γ-氨基丁酸能神经元的活性,但对雌性小鼠无此作用,这导致了小鼠在七氟烷麻醉中存在性别差异。 网络版包含补充材料,可在10.1007/s12264 - 022 - 00825 - w获取。
A growing number of studies have identified sex differences in response to general anesthesia; however, the underlying neural mechanisms are unclear. The medial preoptic area (MPA), an important sexually dimorphic structure and a critical hub for regulating consciousness transition, is enriched with estrogen receptor alpha (ERα), particularly in neuronal clusters that participate in regulating sleep. We found that male mice were more sensitive to sevoflurane. Pharmacological inhibition of ERα in the MPA abolished the sex differences in sevoflurane anesthesia, in particular by extending the induction time and facilitating emergence in males but not in females. Suppression of ERα in vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females. Furthermore, ERα knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia. Collectively, MPA ERα positively regulates the activity of MPA GABAergic neurons in males but not in females, which contributes to the sex difference of mice in sevoflurane anesthesia. The online version contains supplementary material available at 10.1007/s12264-022-00825-w.
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