CX3C-chemokine receptor 1 modulates cognitive dysfunction induced by sleep deprivation.
CX3C-chemokine receptor 1 modulates cognitive dysfunction induced by sleep deprivation.
复制标题
CX3C-趋化因子受体1调节睡眠剥夺引起的认知功能障碍
DOI：
10.1097/cm9.0000000000001769
复制
发表时间：
2021-11-03
影响因子：
6.1
通讯作者：
Pan X
中科院分区：
文献类型：
--
作者：
Xin J;Wang C;Cheng X;Xie C;Zhang Q;Ke Y;Huang X;Chen X;Pan X
摘要背景：小胶质细胞在睡眠剥夺的病理过程中起着不可或缺的作用。在这里，小胶质细胞CX 3C-趋化因子受体1（CX 3CR 1）在调节SD期间的认知下降的潜在作用进行了评估的小胶质细胞神经炎症和突触修剪。在这项研究中，我们的目的是验证CX 3CR 1基因敲除对小胶质细胞功能的干扰是否会影响CNS对SD的反应。研究方法：中年野生型（WT）C57 BL/6和CX 3CR 1 −/−小鼠要么进行SD，要么允许正常睡眠（S）8小时，以模拟中年人熬夜后的病理生理变化。然后通过行为学和组织学实验探讨其不同的变化。结果：与WT组不同，CX 3CR 1缺陷可预防SD诱导的认知障碍。与CX 3CR 1 −/− S组相比，CX 3CR 1 −/− SD小鼠报告了齿状回（DG）中小胶质细胞和细胞癌基因fos密度显著降低，促炎细胞因子表达减少，小胶质细胞吞噬相关因子减少，而海马中抗炎细胞因子水平升高，DG棘密度显著增加。结论：CX 3CR 1缺陷导致不同的脑行为和对SD的反应。炎症衰减活性和突触修剪的相关修饰是可能的机制候选者，这表明CX 3CR 1作为预防睡眠丧失诱导的认知障碍的候选治疗靶点。
Abstract Background: Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD. Methods: Middle-aged wild-type (WT) C57BL/6 and CX3CR1−/− mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. Results: CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1−/− S group, the CX3CR1−/− SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. Conclusions: These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.