Exploring differences in gene expression and relative cell-type balance in the hippocampus of a selectively bred rat model for internalizing and externalizing psychiatric disorders

Birt I, Hagenauer MH, Aydin C, Blandino P, Thompson RC, Clinton SM, Stead J, Akil H, Watson SJ
Society for Neuroscience. 2017.


For many years our laboratory has been exploring hippocampal gene expression differences between selectively-bred high responder (HR) and low responder (LR) rats in order to provide insight into the biology underlying mood and temperament. In total, as part of different experiments run across 53 generations of selective breeding, we have collected eight different microarray or RNA-Seq datasets from samples of the whole hippocampus of HR and LR rats. Recently, we ran a formal meta-analysis to determine which molecular candidates are indicated repeatedly across these different datasets. Using the statistical program R, we re-analyzed six separate HR/LR datasets, and also used the results from previous analyses of an additional two datasets. We included datasets from studies that observed gene expression across several developmental age groups: P7, P14, P21, and adult. In addition, there was a special focus on observing differences in relative cell type expression across phenotype through the use of a cell type-based matrix deconvolution. For the comprehensive analysis, a meta-analysis of effect sizes using a random effects model was performed on both adult and developmental data. Results indicate major differences in the expression of genes with known relationships to various mood disorders, as well as potential differences in immune activation in the LR rats, supporting the theory of altered immune function in the pathophysiology of internalizing disorders.