LAUSR

This study was aimed to examine the effects of sericin administration on restraint stress induced anxiety- and depressive-like behaviors, oxidative stress, inflammation and apoptosis in the prefrontal cortex (PFC) and hippocampus (HIP) of mice. Animals were subjected to chronic restraint stress (3 h/day for 21 days) to induce a depressive-like model. Sericin was administered at different doses (100, 150, and 200 mg/kg/day, gavage for 21 days) along with immobilization. Elevated plus maze (EPM) and open field test (OFT) were performed to assess anxiety; while, the forced swim test (FST) and tail suspension test (TST) were implemented to evaluate depressive-like behaviors. Mitochondrial membrane potential (MMP), and markers of oxidative stress, neuroinflammation, and apoptosis were evaluated in the PFC and HIP regions. Moreover, serum levels of corticosterone were measured. Results showed that sericin increased number of central entries in OFT and prolonged time spent in open arms of EPM apparatus, while it reduced immobility time in TST and FST. Moreover, sericin treatments decreased oxygen species (ROS) and lipid peroxidation levels, restored MMP, and enhanced total antioxidant capacity (TAC) and enzyme activity of GPx and SOD in both brain regions. Furthermore, sericin reduced serum corticosterone concentration and suppressed neuroinflammatory response in the HIP and PFC, shown by decreased NF-κB, TNF-α, and IL-1β protein levels. Finally, sericin inhibited mitochondrial-dependent apoptosis pathway through down-regulation of Bax, cytochrome c, caspase-9 and -3, and up-regulation of Bcl-2 protein. These findings provide evidence for the protective effect of sericin therapy against psychopathological and behavioral changes induced by restraint stress.