Transgenerational Social Stress Alters Immune-Behavior Associations and the Response to Vaccination.

Alexandria Hicks-Nelson,Benjamin C Nephew,Kursat Gurel,Rachel Cooper,Gillian Beamer

doi:10.3390/brainsci7070089

Alexandria Hicks-Nelson, Benjamin C Nephew + Show 3 more

Open Access

https://doi.org/10.3390/brainsci7070089

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Journal: Brain sciences	Publication Date: Jul 21, 2017
Citations: 8	License type: CC BY 4.0

Affiliation: Tufts University

Abstract

Similar to the multi-hit theory of schizophrenia, social behavior pathologies are mediated by multiple factors across generations, likely acting additively, synergistically, or antagonistically. Exposure to social adversity, especially during early life, has been proposed to induce depression symptoms through immune mediated mechanisms. Basal immune factors are altered in a variety of neurobehavioral models. In the current study, we assessed two aspects of a transgenerational chronic social stress (CSS) rat model and its effects on the immune system. First, we asked whether exposure of F0 dams and their F1 litters to CSS changes basal levels of IL-6, TNF, IFN-γ, and social behavior in CSS F1 female juvenile rats. Second, we asked whether the F2 generation could generate normal immunological responses following vaccination with Mycobacterium bovis Bacillus Calmette–Guérin (BCG). We report several changes in the associations between social behaviors and cytokines in the F1 juvenile offspring of the CSS model. It is suggested that changes in the immune–behavior relationships in F1 juveniles indicate the early stages of immune mediated disruption of social behavior that becomes more apparent in F1 dams and the F2 generation. We also report preliminary evidence of elevated IL-6 and impaired interferon-gamma responses in BCG-vaccinated F2 females. In conclusion, transgenerational social stress alters both immune–behavior associations and responses to vaccination. It is hypothesized that the effects of social stress may accumulate over generations through changes in the immune system, establishing the immune system as an effective preventative or treatment target for social behavior pathologies.

Highlights

The application of cutting edge techniques to animal models with limited ethological and/or translanational relevance is a limitation to the development of more effective treatments for social behavior disorders
It is suggested that changes in the immune–behavior relationships in F1 juveniles indicate the early stages of immune mediated disruption of social behavior that becomes more apparent in F1 dams and the F2 generation
There were no effects of chronic social stress (CSS) on F1 female juvenile basal plasma IL-6, tumor necrosis factor (TNF), or IFN-γ levels (Table 2)

Summary

Introduction

The application of cutting edge techniques to animal models with limited ethological and/or translanational relevance is a limitation to the development of more effective treatments for social behavior disorders. A major challenge in studying the transgenerational development of social behavior psychopathology is that initiating events are difficult to identify and separate from transgenerational consequences. This area benefits from the study of multigenerational rodent models, where initiation and consequences can be separated allowing identification of underlying mechanisms and designing appropriate interventions

Methods

Discussion

Conclusion