Depression is a prevalent mood disorder responsible for reduced quality of life for over 264 million people. Depression commonly develops during adolescence and becomes twice as prevalent in females than in males. However, the mechanisms underlying adolescent depression onset and sex differences in the prevalence rate remain unclear. Adolescent exposure to stress and subsequent sensitization of the hypothalamic-pituitary-adrenal (HPA) axis contributes to mood disorder development, and females are particularly vulnerable to HPA sensitization. Repeated exposure to stressors common to adolescent development, like sleep disruption, could partially be responsible for adolescent female susceptibility to depression. To address this possibility, 80 adolescent and adult CD-1 mice (Male, n = 40; Female, n = 40) were manually sleep disrupted for the first four hours of each rest cycle or allowed normal rest for eight consecutive days. Depression-like behavior was assessed with the forced swim test. 5-HT_1A and glucocorticoid receptor expression and concurrent cellular activation via glucocorticoid receptor/c-Fos colocalization were examined in various brain regions to assess cellular correlates of depression and HPA-axis activation. Both adolescent male and female mice displayed significantly greater depression-like behavior and prelimbic c-Fos expression after chronic sleep disruption than non-sleep disrupted adolescent and sleep disrupted adult counterparts. However, sleep disrupted adolescent females demonstrated greater dorsal raphe 5-HT_1A expression than sleep disrupted adolescent males. Adolescent females and males had decreased medial prefrontal 5-HT_1A expression after chronic sleep disruption, but only adolescent females expressed decreased hippocampal 5-HT_1A expression compared to controls. Chronic sleep disruption significantly increased corticosterone release, glucocorticoid expression in the CA1, and activation of glucocorticoid immunoreactive cells in the prelimbic cortex of adolescent females but not in adolescent males. These findings suggest that chronic sleep disruption during adolescence could give rise to depressive symptoms in male and female adolescents through differing signaling mechanisms.

抑郁症是一种普遍的情绪障碍，导致超过 2.64 亿人的生活质量下降。抑郁症通常发生在青春期，女性的患病率是男性的两倍。然而，青少年抑郁症发病的机制和患病率的性别差异仍不清楚。青少年暴露于压力和随后的下丘脑-垂体-肾上腺 (HPA) 轴敏感会导致情绪障碍的发展，而女性特别容易受到 HPA 敏感的影响。反复接触青少年发育常见的压力源，如睡眠中断，可能是青少年女性易患抑郁症的部分原因。为了解决这种可能性，80 只青少年和成年 CD-1 小鼠（雄性，n = 40；雌性，n = 40) 在每个休息周期的前四小时被手动中断睡眠，或允许连续八天正常休息。用强迫游泳测试评估抑郁样行为。5-羟色胺_1A和糖皮质激素受体表达以及通过糖皮质激素受体/c-Fos 共定位的并发细胞激活在不同的大脑区域进行了检查，以评估抑郁症和 HPA 轴激活的细胞相关性。与非睡眠中断的青春期和睡眠中断的成年小鼠相比，青春期雄性和雌性小鼠在慢性睡眠中断后表现出显着更高的抑郁样行为和前肢 c-Fos 表达。然而，睡眠中断的青春期女性表现出比睡眠中断的青春期男性更大的中缝背侧 5-HT _1A表达。慢性睡眠中断后，青春期女性和男性的内侧前额叶 5-HT _1A表达降低，但只有青春期女性的海马 5-HT 表达降低_1A表达与对照相比。慢性睡眠中断显着增加了皮质酮释放、CA1 中糖皮质激素的表达，以及青春期女性前叶皮层中糖皮质激素免疫反应细胞的激活，但在青春期男性中则不然。这些研究结果表明，青春期的慢性睡眠中断可能通过不同的信号机制在男性和女性青少年中引起抑郁症状。