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Several studies have demonstrated the neuroprotective effect of enriched environment (EE) and its positive effect on cognitive performance in pathological conditions, such as neurodegenerative diseases, epilepsy, and traumatic brain injury. However, the immunomodulatory effect of EE in normal rodents is not well characterized. To assess the immunomodulatory effect of EE, we randomly assigned normal mice to EE housing or standard environmental (SE) housing for 3 weeks. Behavioral alterations were evaluated by open field, fear conditioning, and Morris water maze tests. Immunohistochemical staining was performed to assess the expression of behavioral-related proteins, and enzyme-linked immunosorbent assay (ELISA) for brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) was also performed. We also measured the levels of RIP1 and RIP3 proteins using western blotting. EE significantly improved the cognitive performance which was associated with the increased expressions of BDNF, ionized calcium-binding adapter molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP); EE did not influence any morphological changes in the brain tissue in adult mice; however, increased resistance to inflammation induced by TNF-α was observed. These findings indicate that EE can positively influence cognitive and behavioral performance in healthy adult mice by exerting environ-immuno effect on neural function.

Enriched environment improves behavioral performance and attenuates inflammatory response induced by TNF-α in healthy adult mice