The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling.
The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling.
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DOI：
10.1038/s41467-022-35068-w
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发表时间：
2022-12-07
影响因子：
16.6
通讯作者：
Gould, Elizabeth
中科院分区：
文献类型：
--
作者：
Laham, Blake J.;Murthy, Sahana S.;Hanani, Monica;Clappier, Mona;Boyer, Sydney;Vasquez, Betsy;Gould, Elizabeth
早期生活逆境（ELA）增加了神经精神诊断的可能性，这在女性中比男性更普遍。由于生殖激素水平的变化也会增加女性焦虑障碍的可能性，我们研究了ELA对整个发情周期的成年雌性小鼠的影响。我们发现，在孕酮水平相对较高的妊娠期，ELA小鼠表现出更多的回避行为和腹侧海马（vHIP）的θ波振荡功率增加。我们还发现，与对照饲养的小鼠相比，diestrus ELA小鼠在vHIP中具有较高的孕酮水平和较低的异孕酮水平，异孕酮是孕酮的一种神经类固醇代谢物。孕酮受体拮抗剂使ELA小鼠的回避行为正常化，而异孕酮负变构调节剂则促进了对照组小鼠的回避行为。这些结果表明，在灾难期间改变的vHIP孕酮和异孕酮信号会增加ELA小鼠的回避行为。早期生活逆境（ELA）会导致焦虑症，这在女性中比男性更普遍，也更容易使人衰弱。在这里，作者揭示了ELA如何与海马体中的神经类固醇合成相互作用，以驱动雌性小鼠的回避行为。
Early-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes in reproductive hormone levels can also increase the probability of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when progesterone levels are relatively high, ELA mice exhibit increased avoidance behavior and increased theta oscillation power in the ventral hippocampus (vHIP). We also found that diestrus ELA mice had higher levels of progesterone and lower levels of allopregnanolone, a neurosteroid metabolite of progesterone, in the vHIP compared with control-reared mice. Progesterone receptor antagonism normalized avoidance behavior in ELA mice, while treatment with a negative allosteric modulator of allopregnanolone promoted avoidance behavior in control mice. These results suggest that altered vHIP progesterone and allopregnanolone signaling during diestrus increases avoidance behavior in ELA mice. Early-life adversity (ELA) can lead to anxiety disorders, which are more prevalent and debilitating in women than men. Here, authors reveal how ELA interacts with neurosteroid synthesis in the hippocampus to drive avoidance behavior in female mice.
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影响因子：
16.2
作者：
Amilhon, Benedicte;Huh, Carey Y. L.;Williams, Sylvain
通讯作者：
Williams, Sylvain
影响因子：
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Bangasser, Debra A.;Shors, Tracey J.
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Dunn EC;Nishimi K;Gomez SH;Powers A;Bradley B
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作者：
Dunn EC;Nishimi K;Powers A;Bradley B
通讯作者：
Bradley B
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作者：
Corpechot, C;Collins, BE;Fry, JP
通讯作者：
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