Experimental diffuse brain injury and a model of Alzheimer's disease exhibit disease-specific changes in sleep and incongruous peripheral inflammation.
Experimental diffuse brain injury and a model of Alzheimer's disease exhibit disease-specific changes in sleep and incongruous peripheral inflammation.
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DOI：
10.1002/jnr.24771
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发表时间：
2021-04
影响因子：
4.2
通讯作者：
Rowe RK
中科院分区：
文献类型：
--
作者：
Saber M;Murphy SM;Cho Y;Lifshitz J;Rowe RK
老年人群（≥65岁）发生阿尔茨海默病（AD）和/或创伤性脑损伤（TBI）的风险最高。使用翻译小鼠模型，我们研究了与正常衰老、TBI和衰老以及AD相关的睡眠障碍和炎症。我们假设与成年小鼠相比，衰老导致睡眠发生显著变化，并且TBI和衰老将导致与AD小鼠相似的睡眠和炎症水平。我们使用16个月大的雌性野生型（WT老龄）和3xTg-AD小鼠，以及2个月大的参考组（WT成年）来评估睡眠变化。WT老龄小鼠通过中线流体冲击接受弥漫性TBI，并且从WT老龄（TBI前和TBI后）和3xTg-AD小鼠收集血液以评估炎症。测试认知行为，并收集组织用于组织学。使用贝叶斯广义相加和混合效应模型进行分析。与成年小鼠相比，正常衰老和AD都导致睡眠增加。与AD小鼠相比，患有TBI的WT老年小鼠比TBI前睡得更多，具有片段化的较短发作。然而，WT老龄小鼠和3xTg-AD小鼠之间在免疫细胞群和血浆细胞因子水平方面的差异是不一致的，认知缺陷是相似的，并且累积睡眠不能预测任一组的炎症或行为。我们的研究结果表明，在年龄相似的个体中，TBI立即引起比AD更深刻的睡眠改变，尽管这两种疾病都可能包括认知障碍。独特的病理性睡眠途径可能存在于老年人谁招致TBI相比，年龄相仿的人谁有AD，这可能保证疾病特异性治疗在临床环境。
Elderly populations (≥65 years old) have the highest risk of developing Alzheimer’s disease (AD) and/or obtaining a traumatic brain injury (TBI). Using translational mouse models, we investigated sleep disturbances and inflammation associated with normal aging, TBI and aging, and AD. We hypothesized that aging results in marked changes in sleep compared with adult mice, and that TBI and aging would result in sleep and inflammation levels similar to AD mice. We used female 16-month-old wild-type (WT Aged) and 3xTg-AD mice, as well as a 2-month old reference group (WT Adult), to evaluate sleep changes. WT Aged mice received diffuse TBI by midline fluid percussion, and blood was collected from both WT Aged (pre- and post-TBI) and 3xTg-AD mice to evaluate inflammation. Cognitive behavior was tested, and tissue was collected for histology. Bayesian generalized additive and mixed-effects models were used for analyses. Both normal aging and AD led to increases in sleep compared with adult mice. WT Aged mice with TBI slept substantially more, with fragmented shorter bouts, than they did pre-TBI and compared with AD mice. However, differences between WT Aged and 3xTg-AD mice in immune cell populations and plasma cytokine levels were incongruous, cognitive deficits were similar, and cumulative sleep was not predictive of inflammation or behavior for either group. Our results suggest that in similarly aged individuals, TBI immediately induces more profound sleep alterations than in AD, though both diseases likely include cognitive impairments. Unique pathological sleep pathways may exist in elderly individuals who incur TBI compared with similarly aged individuals who have AD, which may warrant disease-specific treatments in clinical settings.
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