Huang-Lian-Jie-Du decoction alleviates depressive-like behaviors in dextran sulfate sodium-induced colitis mice via Trem2/Dap12 pathway

作者：Zheng, Jia-Yi; Li, Xiao-Xiao; Lin, Wei-Yao; Su, Shan; Wu, Hai-Cui; Hu, Rui-Dan; Pan, Hua-Feng; Ye, Jiang-Hong^*; Cai, Ye-Feng^*; Zhang, Shi-Jie^*

来源：Journal of Ethnopharmacology, 2023, 315: 116658.

DOI：10.1016/j.jep.2023.116658

• Depression
• Huang-Lian-Jie-Du decoction
• Lateral habenula
• Trem2
• Dap12
• Microglia

Ethnopharmacological relevance: Huang-Lian-Jie-Du decoction (HLJD), a traditional Chinese medicine prescrip-tion, has been implicated as effective in treating colitis, depression and inflammation-related diseases. Whether HLJD decoction could ameliorate colitis-induced depression was still unknown and the underlying mechanism was needed to be clarified.Aim of the study: Our study aimed to explore the effect and the underlying mechanism of HLJD treatment on colitis-induced depression and the involvement of the inflammatory factors and microglial-activated related genes.Materials and methods: The chronic colitis model was established by treating male mice with 1% dextran sulfate sodium (DSS) for 8 weeks. One week after DSS-treated, HLJD decoction was administered orally with 2 and 4 g/ kg daily for 7 weeks. Behavior tests (Open field/Elevated plus maze/Novel object recognition) and TUNEL staining were then assessed. The expression of inflammatory-related genes and microglial dysregulation were measured by RT-PCR and the expression of Trem2, Danp12 and Iba1 were assessed by immunofluorescence methods.Results: Depressive-like behaviors were observed in mice treated with DSS, which suffered colitis. Compared to normal control (NC-V) mice, the density of TUNEL + cells in the habenula (Hb), hippocampus (HIP), and cortex were significantly higher in colitis (DSS-V) mice, especially in Hb. Compared to NC-V and several brain regions, the expression levels of the Il-1 & beta;, Il-10 and Dap12 mRNA were significantly increased in the lateral habenula (LHb) of colitis mice. Moreover, the expression of Trem2, Dap12 and Iba1 were increased in LHb of DSS-V mice. HLJD treatment could alleviate depressive-like behaviors, reduce the density of TUNEL + cells in Hb and the expression of Il-6, Il-10 and Dap12 mRNA in LHb of DSS-V mice. The overexpression of Trem2, Dap12 and Iba1 in LHb of DSS-V mice were reversed after HLJD treatment.Conclusion: These results reveal LHb is an important brain region during the process of colitis-induced depression. HLJD treatment could alleviates depressive-like behaviors in colitis mice via inhibiting the Trem2/Dap12 pathway in microglia of LHb, which would contribute to the precise treatment. It provides a potential mecha-nistic explanation for the effectiveness of HLJD treatment in colitis patients with depression.

• 单位
  广东省人民医院; 广州中医药大学