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从中孕期开始的睡眠剥夺导致小脑蚓部小胶质细胞活化的幼鼠运动协调能力受损。

Sleep deprivation from mid-gestation leads to impaired of motor coordination in young offspring mice with microglia activation in the cerebellar vermis.

机构信息

Department of Child and Adolescent Health, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China.

Department of Pathology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.

出版信息

Sleep Med. 2024 Mar;115:193-201. doi: 10.1016/j.sleep.2024.02.020. Epub 2024 Feb 12.

Abstract

OBJECTIVE

To investigate the effects of mid-pregnancy sleep deprivation (SD) in C57BL/6 J mice on the motor coordination of the offspring and to explore the potential mechanism of microglia activation in the cerebellar vermis of the offspring involved in the induction of impaired motor coordination development.

METHODS

C57BL/6 J pregnant mice were randomly divided into the SD and control groups. SD was implemented by the multi-platform method from first day of the middle pregnancy (gestation day 8, GD8). At postnatal day 21 (PND21), we measured the development of motor behavior and collected cerebellar vermis tissues to observe the activation of microglia by H&E staining, the expression of microglia-specific markers ionized calcium-binding adaptor molecule-1 (Iba-1) and cluster of differentiation 68 (CD68) by immunohistochemical, and interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor -α (TNF-α) by real-time quantitative PCR (RT-qPCR).

RESULTS

In the offspring of SD group, comparing to the control group, the total time of passage and the reverse crawl distance in the balance beam test, and the frequency of falls from the suspension cord was increased; with lower max rotational speed and shorter duration in the rotarod experiment. Further, we found that the microglia of cerebellar vermis tissues emerged an amoeba-like activation. The mean gray value of Iba-1 was lower, the density of positive cells of CD68 and the expression levels of IL-6 and TNF-α were increased.

CONCLUSIONS

The motor coordination of offspring is impaired, accompanying a SD from mid-pregnancy, and the cerebellar vermis showed microglia activation and pro-inflammatory response. It suggested the adverse effects of SD from mid-gestation on the development of motor coordination through the inflammatory response in the cerebellar vermis of the offspring.

摘要

目的

探讨孕中期睡眠剥夺(SD)对 C57BL/6J 小鼠后代运动协调能力的影响,并探讨小脑蚓部小胶质细胞激活在诱导运动协调发育障碍中的潜在机制。

方法

将 C57BL/6J 孕鼠随机分为 SD 组和对照组。SD 组从妊娠第 8 天(GD8)开始采用多平台法实施。在出生后第 21 天(PND21),测量运动行为发育情况,并采集小脑蚓部组织,观察 H&E 染色小脑蚓部小胶质细胞的激活、小胶质细胞特异性标志物离子钙结合衔接分子-1(Iba-1)和分化簇 68(CD68)的表达,以及实时定量 PCR(RT-qPCR)检测白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和肿瘤坏死因子-α(TNF-α)的表达。

结果

与对照组相比,SD 组后代在平衡木试验中的总通过时间和反向爬行距离增加,从悬索上跌落的频率增加;在转棒试验中,最大旋转速度降低,持续时间缩短。此外,我们发现小脑蚓部小胶质细胞呈阿米巴样激活。Iba-1 的平均灰度值降低,CD68 阳性细胞密度增加,IL-6 和 TNF-α 的表达水平升高。

结论

孕中期 SD 可导致后代运动协调能力受损,小脑蚓部出现小胶质细胞激活和促炎反应。这表明孕中期 SD 通过后代小脑蚓部的炎症反应对运动协调发育产生不良影响。

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