Bush Brittany J, Mohamed Affra, Andrews Eva-Jeneé, Cain Gabrielle, Fawole Ayobami, Johnson Hadiya, Arocho Ashton, Qiao Zhimei, Paul Ketema N, Ehlen J Christopher
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Department of Neurobiology, Morehouse School of Medicine, Atlanta, GA, USA.
Neuropsychopharmacology. 2025 May 17. doi: 10.1038/s41386-025-02124-0.
Sleep disturbances and stress have a well-established link with neuropsychiatric illness; however, the nature of this relationship remains unclear. Recently, studies using the mouse social-defeat stress model revealed a causal role for non-rapid eye movement (NREM) sleep in the maladaptive behavioral responses to stress. These results suggest a novel function for NREM sleep; as a response by cortical neurons to mitigate the maladaptive effects of stress. A major limitation in many social defeat studies has been the exclusion of females. Women exhibit a greater prevalence of both affective disorders and sleep disturbances compared to men, thus there is a clear need to understand sleep-stress interactions in females. The present study adapts recently developed female social-defeat stress models to allow social-defeat and EEG in male-female pairs. Our findings duplicate the behavioral responses that occur in other female, nondiscriminatory, and male models of social-defeat stress. Analysis of electroencephalographic (EEG) recordings, before exposure to stress, reveal that resilience is associated with differences in both NREM and REM sleep that are dependent on sex. After social defeat stress, NREM sleep was increased only in resilient males. In females, susceptibility to stress was associated with increased durations in NREM-sleep bouts. A potential cause of these sleep differences was also identified prior to stress exposure, sex differences in recovery from NREM-sleep loss; thus, suggesting an underlying sex-difference in the homeostatic process regulating sleep interactions with social-defeat stress. These findings suggest that NREM sleep quality is lower in resilient females, whereas the amount of REM sleep is decreased in susceptible females-when compared to males of the same behavioral phenotype. Overall, our findings reveal sexual dimorphism in both the sleep characteristics predicting resilience and sleep changes induced by social-defeat stress.
睡眠障碍与压力和神经精神疾病之间的联系已得到充分证实；然而，这种关系的本质仍不清楚。最近，使用小鼠社会挫败应激模型的研究揭示了非快速眼动（NREM）睡眠在对应激的适应不良行为反应中的因果作用。这些结果表明NREM睡眠具有一种新功能；作为皮质神经元的一种反应，以减轻压力的适应不良影响。许多社会挫败研究的一个主要局限性是排除了雌性。与男性相比，女性情感障碍和睡眠障碍的患病率更高，因此显然有必要了解雌性的睡眠 - 压力相互作用。本研究采用最近开发的雌性社会挫败应激模型，以便在雌雄配对中进行社会挫败和脑电图（EEG）监测。我们的研究结果重复了在其他雌性、无歧视性和雄性社会挫败应激模型中出现的行为反应。对应激暴露前脑电图（EEG）记录的分析表明，恢复力与NREM和REM睡眠的差异有关，这些差异取决于性别。社会挫败应激后，仅在有恢复力的雄性中NREM睡眠增加。在雌性中，对应激的易感性与NREM睡眠发作持续时间增加有关。在应激暴露之前还确定了这些睡眠差异的一个潜在原因，即从NREM睡眠剥夺中恢复的性别差异；因此，这表明在调节睡眠与社会挫败应激相互作用的稳态过程中存在潜在的性别差异。这些发现表明，与具有相同行为表型的雄性相比，有恢复力的雌性NREM睡眠质量较低，而易感雌性的REM睡眠量减少。总体而言，我们的研究结果揭示了在预测恢复力的睡眠特征以及社会挫败应激引起的睡眠变化方面的性别二态性。
