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

Kai Wang, Jin Liu, Jialin Xie, Zhongtian Yong,Han Li,Liyan Wang,Na Xia,Tao Bai,Hongxing Wang,Li Wang

SLEEP MEDICINE(2024)

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摘要
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 interleukin4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor -alpha (TNF-alpha) 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-alpha 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.
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关键词
Sleep deprivation,Offspring,Cerebellar vermis,Motor coordination,Microglia activation,Inflammation response
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