Sexually dimorphic effects of estrogen receptor 2 deletion in the dorsal raphe nucleus on emotional behaviors
Sexually dimorphic effects of estrogen receptor 2 deletion in the dorsal raphe nucleus on emotional behaviors
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中缝背核雌激素受体2缺失对情绪行为的性别二态性影响。
DOI：
10.1111/jne.13195
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发表时间：
2022-09-07
影响因子：
3.2
通讯作者：
Xu，Xiao-Hong
中科院分区：
文献类型：
--
作者：
He，Jing;Yan，Jing-Jing;Xu，Xiao-Hong
情绪行为和情感障碍的性别差异已被广泛注意，其中性腺类固醇激素（如雌激素）的性二态分泌被怀疑起作用。然而，对潜在的神经机制仍然知之甚少。我们注意到，雌激素受体2（Esr2或ERβ）的表达，大脑中雌激素信号的关键介质，在中缝背核（DRN）中富集，这是一个参与情绪调节的区域。为了研究DRNEsr2表达是否赋予情感行为的性别特异性易感性或脆弱性，我们产生了Esr2的条件等位基因，允许通过局部注射Cre表达病毒在DRN中位点特异性缺失Esr2。DRN特异性Esr2缺失轻度增加了女性的焦虑行为，如敲除女性在开放区域中心区花费的时间减少所示。相比之下，DRNEsr2缺失对男性的焦虑水平没有影响，正如敲除的男性在开放场地的中心区域和高架十字迷宫的开放臂中花费的时间相当所证明的那样。此外，在尾部悬吊试验中，DRNEsr2缺失以男性偏好的方式减少了不动性，这是一种抑郁样行为。总之，这些结果揭示了DRNEsr2在调节情绪行为中的性别特异性功能，并建议有针对性地操纵DRNEsr2信号传导作为治疗性别偏见情感障碍的潜在治疗策略。
Sex differences in emotional behaviors and affective disorders have been widely noted, of which sexually dimorphic secretion of gonadal steroid hormones such as estrogen is suspected to play a role. However, the underlying neural mechanisms remain poorly understood. We noted that the expression of estrogen receptor 2 (Esr2, or ERβ), a key mediator of estrogen signaling in the brain, was enriched in the dorsal raphe nucleus (DRN), a region involved in emotion regulation. To investigate whether DRNEsr2expression confers sex‐specific susceptibility or vulnerability in emotional behaviors, we generated a conditional allele ofEsr2that allowed for site‐specific deletion ofEsr2in the DRN via local injection of Cre‐expressing viruses. DRN‐specificEsr2deletion mildly increased anxiety behaviors in females, as shown by decreased time spent in the center zone of an open field in knockout females. By contrast, DRNEsr2deletion had no effects on anxiety levels in males, as demonstrated by knockout males spending comparable time in the center zone of an open field and open arms of an elevated‐plus maze. Furthermore, in the tail suspension test, DRNEsr2deletion reduced immobility, a depression‐like behavior, in a male‐biased manner. Together, these results reveal sex‐specific functions of DRNEsr2in regulating emotional behaviors and suggest targeted manipulation of DRNEsr2signaling as a potential therapeutic strategy to treat sex‐biased affective disorders.