Aging reshapes the response to subchronic LPS: cognitive and neuroinflammatory resilience with selective amyloid vulnerability and reduced responsiveness to L-Theanine and aerobic exercise.

Abstract

Aging alters the brain's inflammatory profile, which may influence vulnerability to neuroinflammatory insults and the effectiveness of neuroprotective interventions. This study investigated whether prophylactic administration of L-theanine (LT) and aerobic exercise could attenuate behavioral and molecular changes induced by subchronic systemic lipopolysaccharide (LPS) exposure in aged rats. Three- and eighteen-month-old male Wistar rats received LT, exercise, or both prior to repeated LPS administration. Behavioral assessments included working, recognition, and spatial short-term memory, followed by hippocampal analyses of inflammatory cytokines, the pCREB/CREB ratio, and Aβ₁-₄₂ expression. Both aging and LPS administration in 3-month-old rats impaired working memory, spatial short-term memory, and motor activity compared to young adult controls. Unlike young adult animals, subchronic LPS exposure did not impair cognitive performance in aged rats. LPS exposure resulted in reduced body weight and increased Aβ₁-₄₂ levels, while IL-1β, TNF-α, and the pCREB/CREB ratio remained unchanged in aged rats. Prophylactic LT and/or aerobic exercise produced modest behavioral improvements, enhancing working memory in the Y-maze, but did not significantly alter hippocampal inflammatory cytokines, the pCREB/CREB ratio, or Aβ₁-₄₂ expression in old rats. In conclusion, aged rats exhibited relative resistance to LPS-induced cognitive and inflammatory effects but remained susceptible to amyloid-related changes.