Early-life stress and antidepressants modulate peripheral biomarkers in a gene-environment rat model of depression

Abstract

Background: Availability of peripheral biomarkers for depression could aid diagnosis and help to predict treatment response. The objective of this work was to analyse the peripheral biomarker response in a gene-environment interaction model of depression. Genetically selected Flinders Sensitive Line (FSL) rats were subjected to maternal separation (MS), since early-life trauma is an important antecedent of depression. An open-ended approach based on a proteomic analysis of serum was combined with the evaluation of depression-associated proteins.

Methods: Rats experienced MS and chronically received escitalopram (ESC) or nortryptiline (NOR). Serum proteins were compared by two-dimensional gel electrophoresis. Corticosterone, cytokines, BDNF and C-reactive protein (CRP) were measured by immunoassays.

Results: Comparing FSL with the control Flinders Resistant Line (FRL), Apo-AI and Apo-AIV, alpha1-macroglobulin, glutathione peroxidase and complement-C3 were significantly modulated. Significant increases were detected in leptin, interleukin (IL) 1alpha and BDNF. CRP levels were significantly reduced. The impact of early-life stress was assessed by comparing FSL+MS versus FSL. Apo-E, alpha1-macroglobulin, complement-C3, transferrin and hemopexin were significantly modulated. The effect of stress in antidepressant response was then evaluated. In the comparison FSL+ESC+MS versus FSL+ESC, albumin, alpha1-macroglobulin, glutathione peroxidase and complement-C3 were modulated and significant reductions were detected in IL4, IL6, IL10, CRP and BDNF. By comparing FSL+NOR+MS versus FSL+NOR proteins like Apo-AIV, pyruvate dehydrogenase, alpha1-macroglobulin, transferrin and complement-C3 showed different levels.

Conclusions: Lipid metabolism and immunity proteins were differently expressed in FSL in comparison with FRL. Exposure to MS induced changes in inflammation and transport proteins which became apparent in response to antidepressant treatments. Modulated proteins could suggest biomarker studies in humans.