Sexual differentiation of neural mechanisms of stress sensitivity during puberty.
Sexual differentiation of neural mechanisms of stress sensitivity during puberty.
复制标题
DOI：
10.1073/pnas.2306475120
复制
发表时间：
2023-10-24
影响因子：
11.1
通讯作者：
Trainor, Brian C.
中科院分区：
文献类型：
--
作者：
Wright, Emily C.;Luo, Pei X.;Zakharenkov, Hannah C.;Godoy, Alexandra Serna;Lake, Alyssa A.;Prince, Zhana D.;Sekar, Shwetha;Culkin, Hannah I.;Ramirez, Alison, V;Dwyer, Tjien;Kapoor, Amita;Corbett, Cody;Tian, Lin;Fox, Andrew S.;Trainor, Brian C.
青春期是焦虑出现性别差异的关键时期，但因果机制尚不清楚。我们发现，雄激素在编程行为反应社会失败压力中发挥了关键作用。使用钙成像，我们表明，在终纹（BNST）的床核的神经活动增加的社会威胁，但不是防御反应，如冻结。这些反应在缺乏青春期雄激素暴露的男性中更为普遍。这些观察结果有助于最近的讨论扩展杏仁核的功能和支持的假设，BNST可以编码即时的威胁。我们的研究结果强调了青春期雄激素在决定成年人对社会压力的行为反应方面的重要性。焦虑症是一个主要的公共卫生问题，目前的治疗对许多人来说是不够的。焦虑在女性中比男性更常见，这种差异出现在青春期。生理应激反应的性别差异可能有助于这种变异性。在青春期，性腺激素塑造大脑结构和功能，但这些变化影响压力敏感性的程度尚不清楚。我们研究了青春期雄激素如何塑造加州小鼠（Peromyscus californicus）对社会应激的行为和神经反应，这是研究应激反应性别差异的模型物种。在成年人中，社交失败减少了女性的社交方式，增加了女性的社交警惕性，但对男性没有影响。我们发现，这种性别差异是不存在的青少年，青春期前阉割成年男性社会失败的敏感性。成年人性腺切除术不会改变对失败的行为反应，这表明性腺激素在青春期起作用，以编程成年后对压力的行为反应。中腹侧床核的终纹（BNST）的钙成像显示，社会威胁增加神经活动和青春期前阉割推广这些反应，威胁较小的社会背景。这些结果支持最近的假设，即BNST响应立即威胁。青春期前用非芳香化雄激素双氢睾酮治疗男性和女性，以减少失败对成年人社交方式和警惕性的影响。这些数据表明，在青春期雄激素受体的激活是至关重要的编程行为反应的压力在成年期。
Puberty is a key period when sex differences in anxiety emerge, but causal mechanisms are unknown. We show that androgens play a key role in programming behavioral responses to social defeat stress. Using calcium imaging we show that neural activity in the bed nucleus of the stria terminalis (BNST) is increased by social threats but not defensive responses like freezing. These responses are more generalized in males lacking pubertal androgen exposure. These observations contribute to recent discussions on the function of the extended amygdala and support the hypothesis that the BNST can encode immediate threats. Our findings highlight the importance of pubertal androgens in determining adult behavioral responses to social stress. Anxiety disorders are a major public health concern and current treatments are inadequate for many individuals. Anxiety is more common in women than men and this difference arises during puberty. Sex differences in physiological stress responses may contribute to this variability. During puberty, gonadal hormones shape brain structure and function, but the extent to which these changes affect stress sensitivity is unknown. We examined how pubertal androgens shape behavioral and neural responses to social stress in California mice (Peromyscus californicus), a model species for studying sex differences in stress responses. In adults, social defeat reduces social approach and increases social vigilance in females but not males. We show this sex difference is absent in juveniles, and that prepubertal castration sensitizes adult males to social defeat. Adult gonadectomy does not alter behavioral responses to defeat, indicating that gonadal hormones act during puberty to program behavioral responses to stress in adulthood. Calcium imaging in the medioventral bed nucleus of the stria terminalis (BNST) showed that social threats increased neural activity and that prepubertal castration generalized these responses to less threatening social contexts. These results support recent hypotheses that the BNST responds to immediate threats. Prepubertal treatment with the nonaromatizable androgen dihydrotestosterone acts in males and females to reduce the effects of defeat on social approach and vigilance in adults. These data indicate that activation of androgen receptors during puberty is critical for programming behavioral responses to stress in adulthood.
登录
查看更多内容
在大鼠和人类中持续的恐惧：恐惧与焦虑中的杏仁核的作用。
DOI：
10.1038/npp.2009.109
发表时间：
2010-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
雄性和雌性大鼠青春期内侧前额叶皮层突触数量的变化：对青春期开始的作用。
DOI：
10.1002/syn.21909
发表时间：
2016-09
期刊：
Synapse (New York, N.Y.)
影响因子：
--
作者：
Drzewiecki CM;Willing J;Juraska JM
通讯作者：
Juraska JM
影响因子：
--
作者：
Beesdo, Katja;Bittner, Antje;Wittchen, Hans-Ulrich
通讯作者：
Wittchen, Hans-Ulrich
影响因子：
3.7
作者：
Cooper MA;Clinard CT;Dulka BN;Grizzell JA;Loewen AL;Campbell AV;Adler SG
通讯作者：
Adler SG
影响因子：
3.3
作者：
Asgari, Pardis;McKinney, Ghraer;McCormick, Cheryl M.
通讯作者：
McCormick, Cheryl M.