Neuroprotective potential of selenium nanoparticles and/or physical and mental activities against social isolation-induced depression in a rat model: inflammatory, oxidative stress, apoptotic, and neurotransmission modulatory pathways.

Background: Social isolation (SI), attributable to modern lifestyles and fast-growing technology, is a leading cause of depression. Selenium nanoparticles (Se-NPs) are neuroactive agents owing to their antioxidant and anti-inflammatory activities. Additionally, physical and mental activities (Ph&M) exert neuroprotective effects by optimizing the release of both neurotransmitters and growth factors. However, their neuroprotective effects against SI-induced depression are still poorly investigated. Aim: We aim to explore the neuroprotective effect of Se-NPs, Ph&M, and their combination to guard against the harmful effects of SI-induced depression in a rat model. Methods: Fifty Sprague Dawley rats were randomly allocated into five groups: control, SI, Ph&M, orally administered Se-NPs (0.1 mg/kg), and a combination group. Neuroprotective activity was quantitatively estimated pharmacologically, biochemically, histologically, and behaviorally. Results: SI caused behavioral and biochemical alteration in the rat model, decreasing neurotransmitter levels, increasing the transcription of inflammatory response genes ( Conclusion: Se-NPs and Ph&M, especially their combination, showed promising protective effects against neuroinflammation, oxidative stress, apoptosis and subsequent alterations of test animal behaviors precipitated by SI.