Effect of six weeks of environmental enrichment on oxidative metabolism and hypothalamic mitochondrial markers of adult male mice

Environmental enrichment (EE) is a non-pharmacological strategy that enhances cognitive, sensory, social, and motor stimulation and has been associated with neuroprotective effects. However, its impact on hypothalamic oxidative metabolism and mitochondrial dynamics in adult animals remains unclear. This study investigated whether six weeks of EE modulates redox balance and mitochondrial markers in the hypothalamus of adult male mice. C57BL/6 mice were maintained in a standard environment (SE) or under EE conditions for six weeks, followed by the assessment of oxidative stress biomarkers, antioxidant defenses, mitochondrial enzymatic activity, and gene expression related to mitochondrial function. EE did not affect body weight but increased food intake. Mitochondrial analysis revealed elevated citrate synthase (CS) activity, with no changes observed in the NAD⁺/NADH ratio. EE reduced protein oxidation, while lipid peroxidation remained unchanged. Antioxidant responses were selectively modulated by increasing catalase (CAT) and glutathione S-transferase (GST) activities, while reduces superoxide dismutase (SOD) activity and the redox state, suggesting adaptive redox remodeling. Gene expression analysis revealed increased PGC-1α levels without changes in TFAM, DRP1, or OPA1, indicating enhanced oxidative capacity without alterations in mitochondrial biogenesis or dynamics. Overall, EE promotes metabolic and redox adaptations in the hypothalamus, improving oxidative efficiency and selectively protecting proteins from oxidative damage.