Effect of the modified wendan decoction on hippocampal astrocyte neurotrophy by regulating the TRP-KYN metabolic pathway in depression-model rats

摘要

Objective:To observe the effect of the modified Wendan decoction on the neurotrophic function of hippocampal astrocytes by regulating the tryptophan-kynurenine(TRP-KYN)neuroprotective metabolic pathway in depression-model rats.Methods:A total of 96 Sprague Dawley(SD)rats were randomly divided into the blank group,model group,sham surgery group,neurotoxicity blocker group(blocker 1 for short)group,decoction group,fluoxetine group,blocker 1 plus decoction group,and blocker 1 plus fluoxetine group.Depression in rats of all groups,except for the blank group,was generated by isolation combined with chronic unpredictable mild stress.After corresponding treatments of the rats in each group,the sucrose preference test was performed to evaluate the depressive behaviors of the rats.Serum levels of tryptophan(TRP),kynurenine(KYN),and kynurenic acid(KYNA)were detected via enzyme-linked immunosorbent assay(ELISA);the mRNA/protein expression of hippocampal astrocyte markers,glial fibrillary acidic protein(GFAP)and S100β,was detected via reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry.ELISA and RT-PCR were carried out to detect the levels/mRNA expressions of brain-derived neurotrophic factor(BDNF)and glial-cell-line-derived neurotrophic factor(GDNF),the nutrient secretions of hippocampal astrocytes in rats.Results:Compared to the blank group,the number of activities of rats was significantly reduced,and the GFAP expression in the hippocampus was significantly increased while the BDNF and GDNF expressions were significantly decreased in the model group.With the intervention of the modified Wendan decoction,the depression of rats was significantly improved,and the BDNF and GDNF expressions in the hippocampus were increased while the GFAP expression was decreased significantly in the model group.Conclusion:The modified Wendan decoction may improve the neurotrophic function of rats’hippocampal astrocytes by enhancing the neuroprotective function of the TRP-KYN pathway,thereby exerting an antidepressant effect.