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Transient neonatal sleep fragmentation results in long-term neuroinflammation and cognitive impairment in a rabbit model.

一过性新生儿睡眠碎片导致兔模型长期神经炎症和认知障碍。

  • 影响因子:4.30
  • DOI:10.1016/j.expneurol.2020.113212
  • 作者列表:"Bertrand SJ","Zhang Z","Patel R","O'Ferrell C","Punjabi NM","Kudchadkar SR","Kannan S
  • 发表时间:2020-01-24
Abstract

:Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.

摘要

: 睡眠碎片是睡眠-觉醒转换的增加,而总睡眠时间没有整体减少。睡眠碎片在急性和慢性住院期间有很好的记录,可导致儿童谵妄和记忆问题。睡眠分裂也经常在神经发育障碍中被注意到。然而,独立于疾病的睡眠碎片是如何影响大脑发育和功能的尚不清楚。我们假设在其他健康的动物中,新生儿期的急性睡眠碎片会导致神经炎症,并与认知发育异常有关。在出生后第 3 天的新西兰大白兔试剂盒 (碎片组) 中,采用眶振法碎片睡眠 72 h。为了控制母体分离,假组从 dam 中分离,并维持在相同的条件下,不进行睡眠碎裂。一个天真的对照组仍然与大坝。试剂盒在碎裂后 2-3 周进行行为测试,采用新型物体识别和自发交替 T 迷宫测试,碎裂后 3-50 天处死。睡眠碎裂导致海马和皮质小胶质细胞形态的急性和慢性变化,促炎和抗炎细胞因子 mRNA 表达的区域差异在 3, 碎裂后 7 天和 50 天。在片段化试剂盒中观察到受损的新物体识别和 T 迷宫任务完成的较长潜伏期。尽管在这些试剂盒中观察到 2 个月大的睡眠结构正常化。结果表明,短暂的新生儿睡眠碎片会导致大脑的短期和长期免疫改变,以及在长期认知任务中的表现减弱。

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影响因子:4.30
发表时间:2020-01-24
来源期刊:Experimental neurology
DOI:10.1016/j.expneurol.2020.113212
作者列表:["Bertrand SJ","Zhang Z","Patel R","O'Ferrell C","Punjabi NM","Kudchadkar SR","Kannan S"]

METHODS::Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.

翻译标题与摘要 下载文献
影响因子:1.52
发表时间:2020-01-27
来源期刊:World neurosurgery
DOI:10.1016/j.wneu.2020.01.108
作者列表:["Middlebrooks EH","Lin C","Okromelidze L","Lu CQ","Tatum WO","Wharen RE Jr","Grewal SS"]

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