Progressive Blood–Brain Barrier Disruption in Sleep-Restricted Young Mice: Cellular Senescence and Neuroinflammation Crosstalk
Por:
Avilez-Avilez J.J., García-Aviles J.E., Ramírez-Carreto R.J., Salas-Venegas V., Guzmán-Ruiz M.A., Medina-Flores F., Königsberg M., Chavarría A., Gómez-González B.
Publicada:
1 ene 2025
Resumen:
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-a (TNF-a), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6) increased in a region-dependent form. Furthermore, the progressive increase of the senescence markers ß-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. © The Author(s) 2025.
Filiaciones:
Avilez-Avilez J.J.:
Posgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico
Área de Neurociencias, Departamento de la Biología de la Reproducción, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico
García-Aviles J.E.:
Posgrado en Biología Experimental, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, Mexico
Ramírez-Carreto R.J.:
Facultad de Medicina, Unidad de Investigación en Medicina Experimental “Dr. Ruy Pérez Tamayo”, Universidad Nacional Autónoma de México, Mexico City, Mexico
Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
Salas-Venegas V.:
Facultad de Medicina, Unidad de Investigación en Medicina Experimental “Dr. Ruy Pérez Tamayo”, Universidad Nacional Autónoma de México, Mexico City, Mexico
Programa de Becas Postdoctorales, Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México, Mexico City, Mexico
Guzmán-Ruiz M.A.:
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, Mexico
Medina-Flores F.:
Cell Biology Department, Emory University, Atlanta, GA, United States
Königsberg M.:
Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico
Chavarría A.:
Facultad de Medicina, Unidad de Investigación en Medicina Experimental “Dr. Ruy Pérez Tamayo”, Universidad Nacional Autónoma de México, Mexico City, Mexico
Gómez-González B.:
Área de Neurociencias, Departamento de la Biología de la Reproducción, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico
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