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.

Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress

“…43,45,56,57 Our results are consistent with previous results showing chronic stress disrupts spleen morphology. [43][44][45][46][47]60 Although the spleen is a blood filter and fixation was conducted through the circulatory system, if altered spleen morphology affects filtration through the spleen to impact fixation quality, the result is the same-functional deficits contributing to fragmentation supports the determination that spleen dysfunction occurs following chronic stress.…”

The clinical significance of collagen family gene expression in esophageal squamous cell carcinoma

“…In the survival analysis, COL6A5 and COL18A1 were validated to be significantly related to overall survival of ESCC patients. Previous studies demonstrated that the COL6A5 expression was significantly associated with depressed behavior and atopic dermatitis (Söderhäll et al, 2007; Zhan et al, 2017), but no articles manifested its correlation with cancer. In addition, COL18A1 has been proved to be a promising biomarker for ovarian cancer and was possibly involved in the progression of bladder cancer (Fang et al, 2013; Peters et al, 2005).…”

Triazophos induced neuro-splenic toxicity and evaluation of antioxidative potential of aqueous Broccoli extract in Wistar albino rats

“…Zhan et al, 2017) and brain(Ren et al, 2011) health from toxic chemicals and other stressinducing factors. Elevated LPO levels, in terms of MDA, in TZ-treated rats was reversed in all BE+TZ group rats, suggest that BE can reduce lipid peroxidation by increasing the activity of the antioxidant enzyme and improving the free radical clearance ability of the Effect of TZ and Broccoli extract treatment on brain biochemical stress.…”