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

• Published in: Neurochemical research Vol. 50; no. 5; p. 269
• Main Authors: Avilez-Avilez, Jessica J., García-Aviles, Jesús Enrique, Ramírez-Carreto, Ricardo Jair, Salas-Venegas, Verónica, Guzmán-Ruiz, Mara A., Medina-Flores, Fernanda, Königsberg, Mina, Chavarría, Anahí, Gómez-González, Beatriz
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2025; Springer Nature B.V
• Subjects: Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Brain; Cell Biology; Cerebral cortex; Complement component C3; Cyclin-dependent kinases; Cytokines; Enzymes; Galactosidase; Glial fibrillary acidic protein; Hippocampus; Inflammation; Interleukin 1; Interleukin 6; Interleukins; Internet resources; Kinases; Laboratories; Membrane permeability; Neurochemistry; Neurology; Neuronal-glial interactions; Neurosciences; Neurotoxicity; Permeability; Phenotypes; Protease inhibitors; Proteins; Senescence; Sleep deprivation; Sodium; Tissues; Tumor necrosis factor-TNF; Tumor necrosis factor-α; β-Galactosidase; Astrogliosis; Neuroinflammation; Sleep restriction; Cellular senescence; Blood–brain barrier
• ISSN: 0364-3190; 1573-6903; 1573-6903
• DOI: 10.1007/s11064-025-04510-y

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