Dopamine System, NMDA Receptor and EGF Family Expressions in Brain Structures of Bl6 and 129Sv Strains Displaying Different Behavioral Adaptation.

Jane Varul,Jürgen Innos,Kattri-Liis Eskla,Mari-Anne Philips,Mario Plaas,Maria Piirsalu,Eero Vasar,Tanel Visnapuu

doi:10.3390/brainsci11060725

Abstract

C57BL/6NTac (Bl6) and 129S6/SvEvTac (129Sv) mice display different coping strategies in stressful conditions. Our aim was to evaluate biomarkers related to different adaptation strategies in the brain of male 129Sv and Bl6 mice. We focused on signaling pathways related to the dopamine (DA) system, N-methyl-D-aspartate (NMDA) receptor and epidermal growth factor (EGF) family, shown as the key players in behavioral adaptation. Mice from Bl6 and 129Sv lines were divided into either home cage controls (HCC group) or exposed to repeated motility testing and treated with saline for 11 days (RMT group). Distinct stress responses were reflected in severe body weight loss in 129Sv and the increased exploratory behavior in Bl6 mice. Besides that, amphetamine caused significantly stronger motor stimulation in Bl6. Together with the results from gene expression (particularly Maob), this study supports higher baseline activity of DA system in Bl6. Interestingly, the adaptation is reflected with opposite changes of DA markers in dorsal and ventral striatum. In forebrain, stress increased the gene expressions of Egf-Erbb1 and Nrg1/Nrg2-Erbb4 pathways more clearly in 129Sv, whereas the corresponding proteins were significantly elevated in Bl6. We suggest that not only inhibited activity of the DA system, but also reduced activity of EGF family and NMDA receptor signaling underlies higher susceptibility to stress in 129Sv. Altogether, this study underlines the better suitability of 129Sv for modelling neuropsychiatric disorders than Bl6.

Highlights

Mice are widely applied to address the neurobiology of psychiatric disorders in animal models
We suggest that inhibited activity of the DA system, and reduced activity of epidermal growth factor (EGF) family and NMDA receptor signaling underlies higher susceptibility to stress in 129Sv
In Bl6 mice, acute treatment with amphetamine (AMPH), an indirect dopamine (DA) agonist, significantly augments locomotor activity and striatal DA efflux compared to 129Sv, but there are no differences in basal DA levels [6]

Summary

Introduction

Mice are widely applied to address the neurobiology of psychiatric disorders in animal models. Both inbred lines, Bl6 and 129Sv, are acknowledged mouse strains in biomedical and transgenic research. We established two differently responding sub-groups among 129Sv: one responded to the acute AMPH group (weak responders), and in the other one the response was 5-fold augmented (strong responders). Such a vast behavioral variation in the response to AMPH in 129Sv was not evident in Bl6 mice [7]. According to literature there might be variations in the genetic and behavioral phenotype among Bl6 and 129Sv sub-strains [8]

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