Environmental enrichment alleviates chronic unpredictable stress-induced cognitive dysfunction in male rats and is associated with alterations in BDNF/TrkB signaling.

Chronic unpredictable mild stress (CUMS) is known to negatively impact hippocampus-dependent memory performance. Environmental enrichment (EE) improves memory and neural architecture. Our study aimed to determine the effects of EE on memory performance and neuroinflammation in CUMS-treated rats. Thirty-two 3-month-old male Wistar-Albino rats were randomly assigned to four groups (n = 8): control, CUMS, CUMS + EE, and EE group. The CUMS procedure was performed in standard cages using random stressors, while the EE procedure was performed in literature-compliant cages for 21 days. Animals were subjected to Novel Object Recognition (NOR) and Morris Water Maze (MWM) tests to assess their memory performance. At the end of the experiment, hippocampus and prefrontal cortex (PFC) tissues were isolated, and ELISA and biochemical studies were performed. Levels of BDNF (Brain-Derived Neurotrophic Factor), TrkB (Tropomyosin Receptor Kinase-B), IL-1β (Interleukin-1β), IL-6 (Interleukin-6), NF-κB (Nuclear Factor-κB), and TNF-α (Tumor Necrosis Factor-alpha) were investigated in hippocampus and PFC tissues, along with plasma corticosterone levels and brain tissue levels of MDA (malondialdehyde) and GSH (reduced glutathione). Recognition memory assessed by the Novel Object Recognition test was impaired by CUMS and improved by environmental enrichment. Exposure to CUMS was associated with increased corticosterone, hippocampal IL-1β and IL-6 levels, decreased BDNF and TrkB levels, and impaired recognition memory. Environmental enrichment attenuated these alterations and improved recognition memory. These findings suggest that environmental enrichment may protect against stress-induced cognitive dysfunction and is associated with modulation of oxidative stress, selected inflammatory markers, and BDNF/TrkB signaling.