ABSTRACT
Objective To explore the relationship between vitamin D and depression and the effects of chronic unpredictable mild stress (CUMS) plus sertraline on vitamin D metabolism in rat brain.Methods Male SD rats were randomly divided into normal control group,normal control + sertraline group,CUMS group and CUMS+sertraline group.CUMS was used to build the animal model of depression.After chronic exposure to CUMS or sertraline (8 mg·kg-1·d-1) for 6 weeks,behavioral response (sucrose preference test) and vitamin D metabolism in the prefrontal cortex were analyzed.Results Compared with normal control group,6 weeks of CUMS procedure induced the rats to a depression-like state,decreased weight and sucrose preference,and increased the expression of enzymes involved in vitamin D activation and catabolism (CYP27B1 and CYP24A1,respectively) and vitamin D receptor (VDR) in rat prefrontal cortex.As compared with CUMS group,CYP27B1,CYP24A1 and VDR were significantly decreased in CUMS+sertraline group (P<0.01 or P<0.05).Conclusion CUMS activates vitamin D signaling in the brain of the animal models of depression,while sertraline alleviates depressive behavior and relieves stress-induced activation of vitamin D signaling,indicating that vitamin D signaling may be involved in the stress-induced depression.
ABSTRACT
Objective To investigate the effects of lipopolysaccharide(LPS) on the tryptophan-kynurenine(TRP) metabolic pathway in rat brains and provide new evidence for the relationship between inflammation and depression.Methods Rats in LPS group were given a single dose of 3.5 mg/kg LPS.while the rats in control group were given the same dosage of saline.The dialysis in ventro-hippocampus were collected by microdialysis within 8 hours and then the TRP,KYN and KA were detected by LC-MS/MS.And the expression of indoleamine 2,3-dioxygenase was detected by Western-blot.Results The level of TRP((550.15± 107.96) pmol/L) and KYN ((337.95±62.73) pmol/L) showed a time-dependent increase after administration LPS 4 h compared with the control group(TRP (368.38±59.31) pmol/L,KYN (172.80±43.96) pmol/L),while KA level in the circulation exhibited a trend to decrease,especially at 7 h ((3.47±0.62) pmol/L,P＜0.05).The ratio of KYN/TRP significantly increased at about 5 h (0.69±0.11,P＜ 0.05),and an ratio of KA/KYN (0.02±0.00) was dramatically decreased after administering LPS 4 h compared with the control group (0.05±0.01)(P＜0.05).Most of the analytes showed more dramatic changes around 4 h to 8 h.LPS group(1.48±0.37) increased the protein expression of indoleamine 2,3-dioxygenase compared with the control group(1.00±0.24) (P＜0.01).Conclusions LPS may cause tryptophan metabolic abnormalities and accelerate the way of kynurenine metabolism,leading to decreased the kynurenic acid status.