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 (TLR4 and NF-κB), and consequently increasing the production of the cytokines TNF-α and IL-1β. It also activated the proinflammatory NLRP3/caspase-1 pathway. The ER stress parameters PERK, CHOP, and GRP78 were significantly elevated. Impairment of autophagy and increased neurodegeneration were detected via the decline of AMPK/SIRT-1/Beclin-1 PI3K/AKT gene expression and m-TOR overexpression. Decreased expression of TrkB and CREB mRNA and consequent decline in brain-derived neurotropic factor were recorded. SI caused a drastic drop in Wnt3a and β-catenin levels and increased GSK3β activity affecting neuroplasticity and cognitive functions. Administration of Se-NPs and/or application of Ph&M, especially their combination, provided significant protection against prior SI effects.

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.