Recurrent Sleep Restriction During Aging Induces Early Recognition Memory Impairment, Neuroinflammation, and Blood–Brain Barrier Dysfunction in Female Wistar Rats

Sleep restriction is associated with neuroinflammation, blood-brain barrier (BBB) dysfunction, and cognitive impairment. Although reduced sleep duration in women is well recognized and the impact of sleep disorders is correlated with a higher incidence of neurodegenerative diseases, its consequences during female aging remain poorly understood. Hence, the aim of this study was to evaluate whether recurrent sleep restriction in female rats accelerates aging-related processes, compared with aged females with normal sleep patterns. Female Wistar rats were subjected to sleep restriction for 10 consecutive days, every three months from 6 to 18 months of age. An additional group of 3-month-old rats underwent a single sleep restriction episode as control. BBB permeability, neuroinflammation, cellular senescence, and recognition memory were assessed. Recurrent sleep restriction increased BBB permeability in the cerebral cortex to tracers of different molecular weights and induced hippocampal increase in TNF-α and IL-1β. In contrast, senescence markers showed age- and region-dependent changes, with no clear effect of recurrent sleep restriction in aged animals. A single sleep restriction episode was sufficient to impair recognition memory, whereas recurrent sleep restriction accelerated age-related cognitive decline. These findings indicate that the effects of sleep restriction depend on age and brain region. Moreover, recurrent sleep restriction during life promotes BBB dysfunction and neuroinflammatory alterations associated with increased brain vulnerability in female rats.