Abstract 111: Maternal Separation, a Model of Early Life Stress in Rats, Dysregulates the Renal Vasculature Gene Expression Patterns During Late Nephrogenic Period and Adult Life
We have shown that maternal separation (MatSep) induces permanent alterations in the renal vascular structure, hemodynamics and sympathetic outflow. Environmental stressors are typically associated with abnormal organ development. Recently, we found that MatSep pups show higher levels of plasma corticosterone and renal norepinephrine during postnatal life (p< 0.05). The aim of this study was to investigate the short and long-term effects of MatSep on gene expression patterns of the renal vasculature. MatSep was performed during early postnatal life timeframe (3hr/day). Undisturbed littermates served as control (C). Upon weaning, rats were allowed to grow and develop for several months. Kidney vessels were isolated at postnatal day 10 (PND10, n=5) and 6 months of age (6Mo, n=5) and flash frozen. mRNA was used to perform genome-wide analysis using Affymetrix rat Gene2.0 ST. EBPfc* analysis was conducted using DAVID bioinformatics resources at NIH website. MatSep altered 1108 genes expression (P<0.03, FDR<0.3,Table 1). We found a set of genes upregulated by MatSep at both PND10 and 6Mo, showing long-lasting changes in expression. The uncoupling protein 1 (UCP1), located proximal to the major vascular and nerve conduits to the kidney, was the highest MatSep-induced upregulation (3.9-fold, PND10). UCP1 network of genes were mostly related to cellular organization and metabolic and cardiovascular disease (e.g. GH, AT1R, AT2R, P38 MAPK, IFNγR, VEGF, ApoE). Thus, MatSep influences timing and direction of key genes involved in the renal vascular maturation. Upregulated non-shivering thermogenesis function early in life may be linked to impaired renal function. NIH R00 HL111354
Author Disclosures: K. Chen: None. A.S. Loria: None.
- © 2015 by American Heart Association, Inc.