Department of Psychology, University of Ottawa, Ottawa, Ontario, Canada.
Cardiff University, Cardiff, UK.
Behav Brain Res. 2021 Feb 5;399:113001. doi: 10.1016/j.bbr.2020.113001. Epub 2020 Nov 13.
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 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 expression than sleep disrupted adolescent males. Adolescent females and males had decreased medial prefrontal 5-HT expression after chronic sleep disruption, but only adolescent females expressed decreased hippocampal 5-HT 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.
抑郁症是一种常见的情绪障碍，导致超过 2.64 亿人的生活质量下降。抑郁症通常在青少年时期发展，并在女性中的发病率是男性的两倍。然而，青少年抑郁症发病的机制和性别差异的患病率仍然不清楚。青少年暴露于压力下，随后下丘脑-垂体-肾上腺（HPA）轴的敏化导致情绪障碍的发展，而女性对 HPA 敏化特别敏感。反复暴露于青少年发育过程中常见的应激源，如睡眠中断，可能部分导致青少年女性易患抑郁症。为了研究这种可能性，80 只青春期和成年 CD-1 小鼠（雄性，n = 40；雌性，n = 40）被手动打断第一个休息周期的前四个小时的睡眠，或允许其连续 8 天正常休息。通过强迫游泳试验评估抑郁样行为。检测了不同脑区 5-HT 和糖皮质激素受体的表达以及糖皮质激素受体/c-Fos 共定位的细胞激活情况，以评估抑郁症和 HPA 轴激活的细胞相关性。慢性睡眠中断后，青春期雄性和雌性小鼠均表现出更明显的抑郁样行为和前额叶皮质 c-Fos 表达增加，而未睡眠中断的青春期和睡眠中断的成年对照组则没有。然而，睡眠中断的青春期雌性小鼠的背侧中缝核 5-HT 表达高于睡眠中断的青春期雄性小鼠。慢性睡眠中断后，青春期雄性和雌性小鼠的内侧前额叶皮质 5-HT 表达减少，但只有青春期雌性小鼠的海马体 5-HT 表达与对照组相比减少。慢性睡眠中断显著增加了青春期雌性小鼠而不是青春期雄性小鼠的皮质酮释放、CA1 区的糖皮质激素表达以及前额叶皮质的糖皮质激素免疫反应细胞的激活。这些发现表明，青春期的慢性睡眠中断可能通过不同的信号机制导致男性和女性青少年出现抑郁症状。
