Effects of environmental enrichment on lymph node mitochondrial-redox status and immune response in adult male C57BL/6 mice

Environmental enrichment (EE), an experimental paradigm promoting cognitive, sensory, social, and motor stimulation, has been associated with neuroprotective effects. Although EE modulates immune function, its influence on the basal redox and metabolic environment of lymph nodes remains unclear. This study investigated whether EE induces physiological immunometabolic and redox adaptations in lymph nodes under non-pathological conditions. Adult male C57BL/6 mice were housed for six weeks in either a standard environment (SE) or EE, followed by evaluation of mitochondrial markers, redox balance, antioxidant defenses in axillary lymph nodes, and systemic basal cytokine profiles. EE did not modify citrate synthase activity, indicating preserved mitochondrial content. Both NAD + and NADH levels increased significantly, while the NAD + /NADH ratio remained unchanged. EE reduced lipid peroxidation without affecting protein oxidation and selectively increased catalase activity, whereas superoxide dismutase and glutathione S-transferase activities were unchanged. Non-enzymatic antioxidant defenses were enhanced, with increased reduced glutathione (GSH), and an elevated GSH/GSSG ratio, despite reduced total sulfhydryl levels. EE did not alter most circulating cytokines but selectively reduced interferon-γ (IFN-γ) levels. Overall, EE promoted a redox-optimized and metabolically resilient lymph node environment, characterized by enhanced antioxidant buffering capacity, without inducing broad immune activation or suppression.