Transcription Factor Motifs Associated with Anterior Insula Gene Expression Underlying Mood Disorder Phenotypes

AbstractMood disorders represent a major cause of morbidity and mortality worldwide but the brain-related molecular pathophysiology in mood disorders remains largely undefined. Because the anterior insula is reduced in volume in patients with mood disorders, RNA was extracted from the anterior insula postmortem anterior insula of  mood disorder samples and compared with unaffected controls for RNA-sequencing identification of differentially expressed genes (DEGs) in (a) bipolar disorder (BD;n = 37) versus (vs.) controls (n = 33), and (b) major depressive disorder (MDDn = 30) vs. controls, and (c) low vs. high axis I comorbidity (a measure of cumulative psychiatric disease burden). Given the regulatory role of transcription factors (TFs) in gene expression via specific-DNA-binding domains (motifs), we used JASPAR TF binding database to identify TF-motifs. We f ound that DEGs in BD vs. controls, MDD vs. controls, and high vs. low axis I comorbidity were associated with TF-motifs that are known to regulate expression of toll-like receptor genes, cellular homeostatic-control genes, and genes involved in embryonic, cellular/organ, and brain development. Robus t imaging-guided transcriptomics by using meta-analytic imaging results to guide independent postmortem dissection for RNA-sequencing was applied by targeting the gray matter volume reduction in the anterior insula in mood disorders, to guide independent postmortem identification of TF motifs regula ting DEG. Our...
Source: Molecular Neurobiology - Category: Neurology Source Type: research