(A and B) Mouse hippocampal tissues were harvested, and RNA-seq was subsequently performed. The heatmap shows all genes whose expression was altered in MRL/lpr mice compared with MRL/mpj mice and whose expression was further reversed by MSCT (A). The Venn diagram (B) shows overlapping genes that were significantly upregulated in MRL/lpr mice versus controls and whose expression was reversed by MSCT (downregulated in MSCT-treated mice versus MRL/lpr mice). (C) Heatmap showing the significantly altered genes enriched in “chemokine signaling pathway.” Each column represents an individual group (n = 3 mice/group). The color scale represents the genewise z score calculated from the normalized gene expression levels. Genes are ordered by hierarchical clustering (A and C). (D) Validation of selected genes in a unique set of mice by qPCR (n = 4 mice/group). (E) Validation of CCL8 levels in the serum and hippocampal homogenates of each group by ELISA (n = 6 mice/group). (F) Representative images of FISH for Ccl8 (green) and the neuronal marker Eno2 (red) in hippocampal sections from the indicated mice. Scale bar: 20 μm. (G) Quantitative results for Ccl8⁺ neurons in the hippocampal sections (n = 7 mice/group). (H–J) Evaluation of depression-like behavior in pristane-treated Ccl8^fl/fl and Syn1^Cre;Ccl8^fl/fl mice (n = 9 mice/group). Ten weeks after pristane injection, the mice were subjected to the SPT (H), TST (I), and FST (J). The data are presented as mean ± SEM. *P < 0.05; ***P < 0.001, determined using 1-way ANOVA followed by Tukey’s post hoc test (D and E), or 2-tailed unpaired t test (H–J). NS, not significant; DEGs, differentially expressed genes; SPT, sucrose preference test; TST, tail suspension test; FST, forced swim test. See also Supplemental Figures 7 and 8.