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Genomic assessment of stress in the horse

ABSTRACT: Thanks to the sequencing of the equine genome in 2009, it is now possible to perform genomic analyses in the horse. Thus, we propose to assess chronic stress by a transcriptomic approach. Two groups of yearlings were maintained in impoverished (n=9) or enriched (n=10) social and sensory conditions. The transcriptomic analysis was performed in blood cells after 12 weeks of experimentation. Results were analyzed with the program TELiS in order to identify the biological pathways differentiating the 2 groups. The analysis showed an up-regulation of the factors CREB, ATF and GATA in impoverished conditions that could sign the distress of those animals since the same molecular pathway has been detected in socio-environmental adversity in humans. This transcriptomic analysis provides a biological signature of yearling welfare that completes the behavioral analyses and help to evaluate disease risk.

ORGANISM(S): Equus caballus

PROVIDER: GSE50623 | GEO | 2014/06/30

SECONDARY ACCESSION(S): PRJNA218100

REPOSITORIES: GEO

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Project description:Mental and cognitive health, as well as vulnerability to neuropsychiatric disorders, involve the interplay of genes with the environment during sensitive developmental periods. Genetic and environmental factors contribute to the development and maturation of neurons, synapses, and the resulting brain circuits. Within the hypothalamus, early-life experiences cause changes in the number of excitatory synapses onto corticotropin-releasing hormone (CRH)-expressing neurons in the paraventricular nucleus (PVN). Further, such synaptic changes suffice to induce enduring epigenomic changes within these cells, influencing programs of gene expression. However, the epigenetic mechanisms by which early-life experiences orchestrate transcriptional programs within individual CRH-expressing neurons, with enduring functional consequences, remain unknown. We utilize animal models of an impoverished environment and unpredictable maternal care (in a limited bedding and nesting [LBN] paradigm), which provokes major alterations in cognitive and emotional outcomes. We are focused on the change in gene expression profiles of stress-sensitive CRH-neurons in the PVN following early-life adversity (ELA). Because of the known heterogeneity of CRH-expressing neuronal populations, we are using single-cell RNA sequencing (RNA-seq) to determine differential gene expression associated with early-life adversity and establish the upstream mechanisms and downstream consequences. We found that CRH-expressing populations of neurons in the PVN can be clustered by both their gene expression profiles as well as by their neurotransmitter phenotype. ELA significantly modified gene expression programs in some neuronal clusters more than others, reducing programs of neuronal development and differentiation and enhancing gene families involved in responses to stress and inflammation. The use of single-cell transcriptomics revealed that ELA impacts gene expression profiles in a cell-type specific manner, with distinctive influence on the different clusters and subpopulations of CRH neurons.

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Genomic assessment of stress in the horse

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