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
{"title":"Progressive Blood–Brain Barrier Disruption in Sleep-Restricted Young Mice: Cellular Senescence and Neuroinflammation Crosstalk","authors":"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","doi":"10.1007/s11064-025-04510-y","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04510-y.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s11064-025-04510-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.