Enriched Environment Enhances the Myelin Regulatory Factor by mTOR Signaling and Protects the Myelin Membrane Against Oxidative Damage in Rats Exposed to Chronic Immobilization Stress.

Long-term consequences of stress intervene in normal signaling of the brain leading to many psychological complications. The enriched environment (EE) may potentially ameliorate the stress response in rats. However, the mechanistic understanding of the enriched environment in protecting the myelin membrane from oxidative damage after prolonged exposure to immobilization stress (IS) remains vague. In the current study, we examined the impact of EE by exposing the rats to IS (4 h/day) followed by EE treatment (2 h/day) for 28 days and the activities of ROS, lipid peroxides, and phospholipids were studied, and its influence on the myelin regulatory factor (MyRF) and enzymes linked to sphingolipid was assessed in the forebrain region of myelin membrane. The ROS and lipid peroxidation was increased, and a significant decrease in the antioxidant activities was found in the IS group. IS + EE could reduce oxidative damage and increase the levels of antioxidant activities. The individual phospholipids including sphingomyelin (SM), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidic acid (PA) were decreased in the IS group, while IS + EE exhibited significant increase in the phospholipid classes regardless of the exposure to IS. There was down-regulation in the mRNA levels of MyRF, CERS2, SPLTC2, UGT8, and GLTP, while IS + EE could mitigate the up-regulation in the levels of mRNA of MyRF, CERS2, SPLTC2, UGT8, and GLTP. The protein expression of MOG, PLP1, and mTOR was found to be reduced in the IS group of rats, however, IS + EE revealed significant increase in the expression of these signaling molecules. These results suggest that EE had a positive effect on chronic stress response by protecting the myelin membrane against oxidative damage and increasing the protein synthesis required for myelin membrane plasticity via activation of MyRF and mTOR signaling in the forebrain region of IS exposed rats.