title: Alterations in splenic function and gene expression in mice with depressive-like behavior induced by exposure to corticosterone.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Heqin
authors.initials: H
authors.lastname: Zhan
authors.affiliation: Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Fulin
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhenghang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Jixia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Taizhen
authors.initials: T
authors.lastname: Cui
authors.affiliation: Department of Pathogenic Microorganism, College of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Guangfan
authors.initials: G
authors.lastname: Hai
authors.affiliation: Department of Basic Medical Sciences, College of Sanquan, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Basic Medical Sciences, College of Sanquan, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Yongji
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers; D016000:Cluster Analysis; D003345:Corticosterone / Q000009:adverse effects*; D003863:Depression / Q000209:etiology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D003345:Corticosterone