Behavioral defects induced by chronic social defeat stress are protected by polysaccharides via attenuation of JNK3/PI3K/AKT neuroinflammatory pathway.

Background: The aim of this study was to evaluate the protective effects of polysaccharides (MCP) on depressive-like behaviors.

Methods: The chronic social defeat stress (CSDS) mice model was used to evaluate the effects of MCP and their underlying mechanisms. Social interaction test (SIT), sucrose preference test (SPT), and tail suspension test (TST) were performed for behavioral assessments. Expression levels of inflammation mediators and phosphatidylinositol 3-kinase (PI3K) activity were determined using commercial ELISA kits. The expression of key proteins in the c-Jun N-terminal protein kinase (JNK3)/PI3K/protein kinase B (AKT) pathway were measured using western blot and RT-PCR.

Results: The results showed that chronic administration of MCP (100, 200, 400 mg/kg/day) significantly prevented depressive-like behaviors in CSDS mice as assessed by SIT, TST and SPT. Elevated levels of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)], and expression of JNK3, c-Jun, P-110β proteins were observed in the hippocampus of CSDS mice. Moreover, the activity of PI3K and phosphorylation level of AKT were reduced in the hippocampus of CSDS mice. Interestingly, the administration of MCP reversed these changes. Furthermore, the protective effects of MCP on CSDS mice were partly inhibited by the PI3K inhibitor, LY294002.

Conclusions: In conclusion, the protective effects of MCP against depressive-like behaviors in CSDS mice might be due to a reduction in neuroinflammation and the down-regulation of the JNK3/PI3K/AKT pathway in the hippocampus.