Understanding Brain Aging Through Behavioural and Microglial Changes: A Lifespan Approach

Abstract Aging is characterized by progressive physiological decline linked to inflammaging, a chronic low-grade inflammatory state. This study investigates age-related behavioural changes and their correlation with microglial function in female Sprague Dawley rats across their lifespan. Using a longitudinal design at 2, 6, 12, and 24 months of age, we assessed motor performance, mood-related behaviours, and spatial cognition alongside microglial morphometric analysis in key brain regions. Results showed that motor and cognitive performance began to decline significantly at 12 months, with severe impairments and depressive-like behaviours appearing by 24 months. These deficits were paralleled by progressive gliosis in the hippocampus and striatum. Microglial morphometric analysis further indicated a more reactive, region-dependent phenotype, with cells in the striatum adopting a smaller area, reduced perimeter, and fewer intersections. These findings provide compelling evidence for significant age-dependent deterioration in motor performance, mood regulation, and cognitive abilities in female rats. Our data strongly suggest an underlying progression of neurobiological changes, with microglial dysfunction and neuroinflammation being central candidates. This research contributes valuable insights into the cellular correlates of behavioural decline across the female lifespan, serving as a reference for the multifaceted changes that occur during normal aging.