Alterations in splenic function and gene expression in mice with depressive-like behavior induced by exposure to corticosterone

Zhan,Heqin; Huang,Feng; Yan,Fulin; Zhao,Zhenghang; Zhang,Jixia; Cui,Taizhen; Yang,Fan; Hai,Guangfan; Jia,Xiaoman; Shi,Yongji

doi:10.3892/ijmm.2017.2850

Alterations in splenic function and gene expression in mice with depressive-like behavior induced by exposure to corticosterone

Authors:
- Heqin Zhan
- Feng Huang
- Fulin Yan
- Zhenghang Zhao
- Jixia Zhang
- Taizhen Cui
- Fan Yang
- Guangfan Hai
- Xiaoman Jia
- Yongji Shi
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Affiliations: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China, Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Pathogenic Microorganism, College of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Basic Medical Sciences, College of Sanquan, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
Published online on: January 5, 2017 https://doi.org/10.3892/ijmm.2017.2850
Pages: 327-336
Copyright: © Zhan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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