Does Enriched Environment Improve Chronic Immobilization Stress-Induced Cognitive and Behavioral Changes in Adult Male Rats?

Abstract

Chronic stress induces detrimental effects on cognition, behavior, and hippocampal integrity. An enriched environment (EE) has been shown to enhance learning and memory; however, its role against chronic immobilization stress (CIS)-induced alterations and the underlying mechanisms remain insufficiently explored. This study aimed to investigate the protective effects of EE on CIS-induced behavioral, molecular, and structural changes in the hippocampus of adult male rats. Thirty-two adult male Wistar albino rats were assigned to four groups: control, control + EE, CIS, and CIS + EE. Rats were subjected to CIS (4 h/day) followed by EE exposure (2 h/day) for 28 days. Behavioral assessments were conducted. Serum corticosterone levels, hippocampal brain-derived neurotrophic factor (BDNF), and mRNA expression of aquaporin-4 (AQP4) and glutamate receptors (GluA1 and GluA2) were evaluated. Histopathological, ultrastructural, and immunohistochemical (LC3) examinations were performed. EE significantly ameliorated CIS-induced cognitive and behavioral impairments and restored hippocampal histological and ultrastructural integrity. These effects were associated with reduced serum corticosterone levels, increased hippocampal BDNF levels, and upregulated expression of AQP4, GluA1, and GluA2 mRNA. These findings suggest that EE is a promising non-pharmacological strategy for mitigating stress-induced hippocampal dysfunction and cognitive decline.