National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital/Institute of Mental Health) and the Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing 100191, China.
Chin Med J (Engl). 2019 Jul 5;132(13):1582-1590. doi: 10.1097/CM9.0000000000000279.
Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations. One deleterious effect of early-life stress that manifests in later life is sleep disturbance, but this has not been examined in aged mice and the underlying neural mechanisms remain unknown. Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation, this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities.
Twenty aged male C57BL/6 mice (>16 months, n = 10 per group) were used in this study. During post-natal days 2 to 9, dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed). When the mice were 16 to 17 months old, their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram. The amount of each sleep-wake stage, mean duration, and stage transition was analyzed. Then, five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry. Group comparisons were carried out using Student t test or analysis of variances when appropriate.
Compared with the control mice, the early-life stressed aged mice spent less time awake over 24 h (697.97 ± 77.47 min vs. 631.33 ± 34.73 min, t17 = 2.376, P = 0.030), accordingly, non-rapid eye movement sleep time was increased (667.37 ± 62.07 min vs. 723.54 ± 39.21 min, t17 = 2.326, P = 0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 min vs. 89.39 ± 12.69 min, t17 = 3.277, P = 0.004). Meanwhile, we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1, 16) = 81.04, P < 0.001).
Early adverse experiences disrupt sleep behaviors in aged mice, which might be associated with the excitatory-inhibitory imbalance in the NAc.
早期生活中经历的不良事件可能会深刻重塑大脑的神经发育轨迹，并导致长期的行为和神经改变。早期生活压力的一个有害影响是睡眠障碍，但这在老年小鼠中尚未得到研究，其潜在的神经机制仍不清楚。考虑到伏隔核（NAc）在睡眠-觉醒调节中的重要作用，本研究旨在评估早期生活压力对老年小鼠睡眠行为的影响，以及 NAc 在内源睡眠异常中的潜在作用。
本研究使用了 20 只年龄在 16 个月以上（每组 10 只）的雄性 C57BL/6 老年雄性小鼠。在产后第 2 至 9 天，给予母鼠足够的（对照组）或有限的筑巢和垫料（应激组）。当小鼠 16 至 17 个月大时，使用脑电图和肌电图记录它们 24 小时的睡眠-觉醒行为。分析每个睡眠-觉醒阶段的量、平均持续时间和阶段转换。然后，从每组中随机选择 5 只动物，使用免疫组织化学方法测量 NAc 中囊泡谷氨酸转运体-1（VGluT1）和囊泡 γ-氨基丁酸转运体（VGAT）的表达水平。当适当的时候，使用学生 t 检验或方差分析进行组间比较。
与对照组相比，早期生活压力下的老年小鼠在 24 小时内清醒的时间更少（697.97±77.47 分钟比 631.33±34.73 分钟，t17=2.376，P=0.030），因此非快速眼动睡眠时间增加（667.37±62.07 分钟比 723.54±39.21 分钟，t17=2.326，P=0.033），快速眼动睡眠的平均持续时间延长（73.00±8.98 分钟比 89.39±12.69 分钟，t17=3.277，P=0.004）。同时，我们观察到应激组 NAc 中 VGluT1/VGAT 比值降低（F(1,16)=81.04，P<0.001）。
早期的不良经历扰乱了老年小鼠的睡眠行为，这可能与 NAc 中的兴奋-抑制失衡有关。
