Parallel changes in gene expression in peripheral blood mononuclear cells and the brain after maternal separation in the mouse

Johan H Van Heerden,David Montaner,Nicola Illing,Ana Conesa,Vivienne Russell,Dan J Stein

doi:10.1186/1756-0500-2-195

Abstract

BackgroundThe functional integration of the neuro-, endocrine- and immune-systems suggests that the transcriptome of white blood cells may reflect neuropsychiatric states, and be used as a non-invasive diagnostic indicator. We used a mouse maternal separation model, a paradigm of early adversity, to test the hypothesis that transcriptional changes in peripheral blood mononuclear cells (PBMCs) are paralleled by specific gene expression changes in prefrontal cortex (PFC), hippocampus (Hic) and hypothalamus (Hyp). Furthermore, we evaluated whether gene expression profiles of PBMCs could be used to predict the separation status of individual animals.FindingsMicroarray gene expression profiles of all three brain regions provided substantial evidence of stress-related neural differences between maternally separated and control animals. For example, changes in expression of genes involved in the glutamatergic and GABAergic systems were identified in the PFC and Hic, supporting a stress-related hyperglutamatergic state within the separated group. The expression of 50 genes selected from the PBMC microarray data provided sufficient information to predict treatment classes with 95% accuracy. Importantly, stress-related transcriptome differences in PBMC populations were paralleled by stress-related gene expression changes in CNS target tissues.ConclusionThese results confirm that the transcriptional profiles of peripheral immune tissues occur in parallel to changes in the brain and contain sufficient information for the efficient diagnostic prediction of stress-related neural states in mice. Future studies will need to evaluate the relevance of the predictor set of 50 genes within clinical settings, specifically within a context of stress-related disorders.

Highlights

The functional integration of the neuro, endocrine- and immune-systems suggests that the transcriptome of white blood cells may reflect neuropsychiatric states, and be used as a non-invasive diagnostic indicator
Studies have highlighted the value of using peripheral tissue targets [1,2], an approach based on the functional integration of neural, endocrine- and immune-systems [3]
Energy metabolism (GO:0005739, GO:0051187 and GO:0006099). These results suggest a functional shift in the immune system in peripheral blood mononuclear cells (PBMCs) in MS mice, characterised by the coordinated down-regulation of energy requiring processes, such as protein synthesis and transport

Summary

Introduction

The functional integration of the neuro-, endocrine- and immune-systems suggests that the transcriptome of white blood cells may reflect neuropsychiatric states, and be used as a non-invasive diagnostic indicator. Studies have highlighted the value of using peripheral tissue targets [1,2], an approach based on the functional integration of neural-, endocrine- and immune-systems [3]. Tsuang et al [2] showed that the microarray analysis of peripheral blood samples discriminated between patients clinically diagnosed with schizophrenia or bipolar disorder and healthy controls. It remains to be established whether gene expression changes in peripheral tissue targets are paralleled by specific transcriptional alterations in neural tissues [1]

Methods

Results

Conclusion