Circadian cycle-dependent EEG biomarkers of pathogenicity in adult mice following prenatal exposure to in utero inflammation.

Circadian cycle-dependent EEG biomarkers of pathogenicity in adult mice following prenatal exposure to in utero inflammation.
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DOI:
10.1016/j.neuroscience.2014.06.022
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发表时间:
2014-09-05
期刊:
影响因子:
3.3
通讯作者:
Burd, I.
Burd, I.
中科院分区:
医学3区
文献类型:
--
作者:
Adler, D. A.;Ammanuel, S.;Lei, J.;Dada, T.;Borbiev, T.;Johnston, M. V.;Kadam, S. D.;Burd, I.

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早产儿宫内感染或炎症是不良神经学结局的已知风险,包括认知、运动和行为障碍。我们以前的数据表明,在宫内暴露于脂多糖(LPS)的小鼠模型中存在急性胎脑炎症。我们假设LPS诱导的子宫内炎症在暴露的小鼠中产生神经变性的长期EEG生物标志物,其可以通过使用连续定量视频-EEG-EMG分析来确定。在E17时对妊娠的CD 1母兽进行单次LPS注射。对照母鼠注射相同体积的盐水(LPS n=10,对照n=8)。在出生后P90-100,使用栓系记录系统和植入硬膜下电极进行24小时同步视频/EEG/EMG记录。对治疗组盲法进行行为状态评分,使用同步视频、EMG和EEG迹线特征对每个10秒EEG时期进行评分,以生成个体睡眠图。在清醒与睡眠周期期间,分析自动EEG功率谱的δ和θ-β功率比。对照组和LPS睡眠图均显示超昼夜觉醒/睡眠循环。由于啮齿类动物是夜行动物,对照小鼠显示出预期的昼夜变化,在黑暗周期阶段,清醒状态花费的时间显著更长。相反,LPS处理的小鼠失去了这种昼夜节律。睡眠微结构也显示出显着的变化,特别是在黑暗周期中,LPS小鼠,造成显着较长的平均NREM周期持续时间。在处理组之间未发现Δ功率数据的显著性;然而,在对照组中观察到的θ-β功率比的显著活性依赖性变化在LPS暴露小鼠中不存在。总之,暴露于子宫内炎症的CD 1小鼠导致成年后睡眠结构的显著改变,这是昼夜节律周期和活动状态依赖性的。
Intrauterine infection or inflammation in preterm neonates is a known risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. Our previous data suggest that there is acute fetal brain inflammation in a mouse model of intrauterine exposure to lipopolysaccharides (LPS). We hypothesized that the in utero inflammation induced by LPS produces long-term EEG biomarkers of neurodegeneration in the exposed mice that could be determined by using continuous quantitative video-EEG-EMG analyses. A single LPS injection at E17 was performed in pregnant CD1 dams. Control dams were injected with same volumes of saline (LPS n=10, Control n=8). At postnatal age of P90-100, 24h synchronous video/EEG/EMG recordings were done using a tethered recording system and implanted subdural electrodes. Behavioral state scoring was performed blind to treatment group, on each 10 second EEG epochs using synchronous video, EMG and EEG trace signatures to generate individual hypnograms. Automated EEG power spectrums were analyzed for delta and theta-beta power ratios during wake vs. sleep cycles. Both control and LPS hypnograms showed an ultradian wake/sleep cycling. Since rodents are nocturnal animals, control mice showed the expected diurnal variation with significantly longer time spent in wake states during the dark cycle phase. In contrast, the LPS treated mice lost this circadian rhythm. Sleep microstructure also showed significant alteration in the LPS mice specifically during the dark cycle, caused by significantly longer average NREM cycle durations. No significance was found between treatment groups for the delta power data; however, significant activity dependent changes in theta-beta power ratios seen in controls were absent in the LPS-exposed mice. In conclusion, exposure to in utero inflammation in CD1 mice resulted in significantly altered sleep architecture as adults that were circadian cycle and activity state dependent.
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