Environmental Enrichment Attenuates Aging-Induced BBB Disruption and Cognitive Impairment with Activation of FNDC5/Irisin Signaling.
📄 Abstract
Aging disrupts the neurovascular unit (NVU) and blood-brain barrier (BBB), elevates glial inflammatory tone, and compromises hippocampal memory. Environmental enrichment (EE)-a multimodal, lifestyle-based intervention-improves cognition, but its association with BBB/NVU and FNDC5/irisin-related signaling in aging remains incompletely understood. Aged male C57BL/6J mice (21 months old) were housed under EE or standard conditions for 11 weeks. Hippocampal-dependent spatial working memory was assessed using the radial eight-arm maze, and neuronal (NeuN), glial (Iba1, GFAP), and BBB/NVU markers (AQP4 endfoot polarity, occludin, ZO-1, PECAM-1, microvessel length/density) were quantified. FNDC5/irisin-related signaling was evaluated by measuring PGC-1α, FNDC5/irisin, IGF-1, BDNF,