Antidepressant-like efects and cognitive enhancement of Schisandra chinensis in chronic unpredictable mild stress mice and its related mechanism

The aim of this study was to evaluate whether Schisandra chinensis extract (SCE) administration infuences chronic unpredictable mild stress (CUMS)-induced depression and cognitive impairment,and explores underlying mechanisms. Sucrose preference test (SPT) and forced swimming test(FST) were used for assessing depressive symptoms, and Y-maze, Morris water maze were used for evaluating cognition processes. The results showed that CUMS (4 weeks) was effective in producing both depression and memory defcits in mice. Additionally, CUMS exposure significantly decreased brain derived neurotrophic factor (BDNF) levels in hippocampus as indicated by ELISA,immunohistochemistry and immunofuorescence assays, accompanied by down-regulated tyrosine kinase receptor B (TrkB)/cAMP-response element binding protein (CREB)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthasekinase-3β (GSK-3β) signaling pathways. Chronic administration of SCE (600 or 1200mg/kg, i.g.)signifcantly prevented all these CUMS-induced behavioral and biochemical alterations. It suggested that SCE could improve the depression-like emotional status and associated cognitive defcits in CUMS mice, which might be mediated by regulation of BDNF levels in hippocampus, as well as up-regulating of TrkB/CREB/ERK and PI3K/AKT/GSK-3β pathways.