Abstract

The effect of six different traumatic stress protocols on the transcriptome of the rat adrenal gland was examined using RNA sequencing. These protocols included chronic variable stress, chronic shock, social defeat and social isolation. The response of the transcriptome to stress suggested that there are genes that respond in a universal or stress modality-independent manner, as well as genes that respond in a stress modality-specific manner. Using a small number of the genes selected from the modality-independent set of stress-sensitive genes, a sensitive and robust measure of chronic stress exposure was developed. This stress-sensitive gene expression (SSGE) index could detect chronic traumatic stress exposure in a wide range of different stress models in a manner that was relatively independent of the modality of stress exposure and that paralleled the intensity of stress exposure in a dose-dependent manner. This measure could reliably distinguish control and stressed individuals in the case of animals exposed to the most intense stress protocols. The response of a subset of the modality-specific genes could also distinguish some types of stress exposure, based solely on changes in the pattern of gene expression. The results suggest that it is possible to develop diagnostic measures of traumatic stress exposure based solely on changes in the level of expression of a relatively small number of genes.

Highlights

  • The original description of the stress response by Selye[1] emphasized the nonspecific nature of the response to a range of different stressors

  • The results described in this report demonstrate that there are both common and stress modality-specific transcriptional responses to different traumatic stress protocols in the adrenal gland

  • The common responses presumably reflect the fact that much of the stress response is funneled through the adrenal gland via a small number of signaling pathways[10,11]

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Summary

Introduction

The original description of the stress response by Selye[1] emphasized the nonspecific nature of the response to a range of different stressors. It was shown that, at least in some tissues, the response to different modalities of stress exposure can be distinguished[2,3]. The adrenal gland is the terminal organ for both the HPA axis and the sympathetic adrenomedullary (SAM) system[10,11]. It is, a key tissue in which to ask basic questions about the gene regulatory response to stress, because changes in gene expression in this tissue are likely to be strongly tied to mediating the responses to stress. There is interest in developing biological diagnostic tests for stress exposure and any such test will most likely use peripheral

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