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Depressed patients present with increased cortisol levels and attenuated immune responses. However, little is known about the association between depression and the spleen, as this is the largest peripheral immune organ. In this study, we examined alterations in splenic function and gene expression in mice with depressive-like behavior, well as the expression of certain proteins in related pathways. A mouse model of depression was established with the use of corticosterone. Splenic function and histopathology were assessed using Wright and H&E staining. The Agilent Whole Mouse Genome Oligo Microarray containing >41,174 transcript probes was used to measure the levels of gene-expression in the spleens from control and model mice, and the levels of certain proteins associated with depression were measured by western blot analysis in the brain and spleen separately. We found that splenic function and immunity in the mice with depressive-like behavior were markedly impaired. A total of 53 genes exhibited a differential response in the mice with depressive-like behavior, 11 of which were more notable, including collagen, type VI, α5 (Col6a5), immunoglobulin superfamily, member 11 (Igsf11), D site albumin promoter binding protein (Dbp), tachykinin 2 (Tac2) and γ-aminobutyric acid B receptor 2 (Gabbr2). Pathway analysis revealed that the amino acid biosynthesis and the clock gene pathways were more meaningful among these genes. The levels of GABBR2, DBP and substance P (SP; encoded by the Tac2 gene) related proteins in the brain were markedly downregulated, and similar results were observed in the spleen. The anti-depressant, fluoxetine, reversed the changes in the levels of these proteins. The findings of our study regarding changes occurring in the spleen during depression may indirectly elucidate and shed light into the pathogenesis of depression and depressive-like behavior.

Background: Lactuside B (LB) is a novel active ingredient separated from Pterocypsela elata by our team. In our preliminary study, LB showed a therapeutic effect on depression. However, the underlying molecular mechanisms remain unclear. Objectives: This study was the first to study the pharmacological effects and mechanisms of LB on depression. Materials and Methods: Network pharmacology method was applied to screen the candidate targets and signaling pathways. Furthermore, molecular docking, cell test, and animal experiments were used to confirm the antidepression mechanisms. Results: The network pharmacology results showed 29 targets and 40 signaling pathways of LB on depression. Molecular docking showed that there was a strong binding effect between LB and each target (cAMP response element binding protein B [CREB], Ras, Raf, and ERK1/2). Cell tests indicated that the expressions of Ras and CREB in astrocyte cells (0.05–0.20 g/L of LB) exhibited significant differences (P < 0.05) compared with the model group, respectively. In animal tests, the expressions of Ras, ERK1/2, and Raf (12.5–50.0 μg/10 g of LB) showed a significant difference compared with mice in the model group (P < 0.05). Conclusion: These results indicated that the antidepression mechanism of LB was mainly associated with Ras signaling pathway, and the cAMP signaling pathway and PI3K-Akt signaling pathway may play an essential role. [ABSTRACT FROM AUTHOR]