Progressive Blood–Brain Barrier Disruption in Sleep-Restricted Young Mice: Cellular Senescence and Neuroinflammation Crosstalk

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jessica J. Avilez-Avilez, Jesús Enrique García-Aviles, Ricardo Jair Ramírez-Carreto, Verónica Salas-Venegas, Mara A. Guzmán-Ruiz, Fernanda Medina-Flores, Mina Königsberg, Anahí Chavarría, Beatriz Gómez-González
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Abstract

Sleep loss promotes a chronic low-grade inflammatory status with increased levels of inflammatory cytokines. Sleep loss also induces low-grade neuroinflammation characterized by glial reactivity and blood–brain barrier (BBB) dysfunction, as evidenced by BBB hyperpermeability and tight junction disassembly. Additionally, it raises molecules related to the senescence-associated secretory phenotype (SASP) in aged subjects, suggesting an increase in senescent cells. Here, we assessed the impact of sleep restriction on cellular senescence, neuroinflammation, and BBB function in the cerebral cortex and hippocampus of young male C57BL/6 mice. Sleep restriction induced a progressive increase in BBB permeability after 3, 5, and 10 days, along with a higher expression of the astroglial marker, the glial fibrillary acidic protein (GFAP), and the expression of the C3 complement component. The pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) increased in a region-dependent form. Furthermore, the progressive increase of the senescence markers β-galactosidase and p21 observed in both brain regions was accompanied by a neurotoxic astroglial response. Our data suggest that sleep restriction promotes cellular senescence in the cerebral cortex and hippocampus of young mice.

Graphical Abstract

睡眠受限幼鼠的进行性血脑屏障破坏:细胞衰老和神经炎症串扰
睡眠不足促进慢性低度炎症状态,炎症细胞因子水平升高。睡眠不足还会诱发以神经胶质反应性和血脑屏障(BBB)功能障碍为特征的低度神经炎症,如血脑屏障高通透性和紧密连接破坏。此外,它增加了与衰老相关的分泌表型(SASP)相关的分子,表明衰老细胞的增加。在这里,我们评估了睡眠限制对年轻雄性C57BL/6小鼠大脑皮层和海马细胞衰老、神经炎症和血脑屏障功能的影响。睡眠限制在3、5和10天后诱导血脑屏障通透性进行性增加,同时星形胶质标记物、胶质纤维酸性蛋白(GFAP)和C3补体成分的表达增加。促炎细胞因子肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和白细胞介素-6 (IL-6)以区域依赖的形式增加。此外,在两个脑区观察到衰老标志物β-半乳糖苷酶和p21的进行性增加,并伴有神经毒性星形胶质反应。我们的数据表明,睡眠限制促进了年轻小鼠大脑皮层和海马体的细胞衰老。图形抽象
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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