Early-life stress alters sleep structure and the excitatory-inhibitory balance in the nucleus accumbens in aged mice

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Background: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.Methods:Twenty aged male C57BL/6 mice (> 16 months, n = 10 per group) were used in this study. During postnatal days 2–9, dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed). When the mice were 16–17 months old, their sleep-wake behaviors were recorded over 24 hours using electroencephalogram and electromyelogram. The amount of each sleep-wake stage, mean duration, and stage transition were analyzed. Then, five animals were randomly chosen from each group and were used to measure the expression levels of vesicular transporters of glutamate (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the nucleus accumbens using immunohistochemistry. Group comparisons were carried out using Student's t-tests or analysis of variances when appropriate.Results:Compared with the control mice, the early-life stressed aged mice spent less time awake over 24 hours (697.97 ± 77.47 vs. 631.33 ± 34.73, t17 = 2.376, p = 0.030), accordingly, non-rapid eye movement sleep time was increased (667.37 ± 62.07 vs. 723.54 ± 39.21, t17 = 2.326, P = 0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 vs. 89.39 ± 12.69, t17 = 3.277, P = 0.004). Meanwhile, we observed decreased VGluT1/VGAT ratios in the nucleus accumbens in the stressed group (F(1, 16) = 81.04, P < 0.001).Conclusions:These results suggest that early adverse experiences disrupt sleep behaviors in aged mice, which might be associated with the excitatory-inhibitory imbalance in the nucleus accumbens.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

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