Profiling the Post‐Injury Hippocampal MicroRNA Response to Transient Forebrain Ischemia: Sub‐regional Differences Between Cornu Ammonis‐1 and Dentate Gyrus

Abstract

ObjectivesEven brief periods of ischemia can result in delayed neuronal cell death in hippocampal cornu ammonis‐1 (CA1), resulting in impaired memory and learning, whereas neurons in the adjacent dentate gyrus (DG) are relatively ischemia resistant. Understanding the pathophysiological and molecular mechanisms underpinning the selective ischemic vulnerability of the CA1 may translate to novel clinical interventions improving outcome in survivors of cerebral ischemia. MicroRNAs (miRNAs) are short (~18–25 nucleotides long) non‐coding RNAs that modulate translation of target messenger RNAs. To date, the miRNA expression profiles of hippocampal CA1 and DG sub‐regions in response to forebrain ischemia have not been examined. The objective of the present study was to assess and compare post‐injury miRNA expression patterns between CA1 and DG in a rat model of forebrain ischemia.MethodsAll experiments were conducted in conformance with the FASEB Statement of Principles for the use of Animals in Research and Education. CA1 and DG sub‐regions were dissected from rat hippocampi following a 10‐minute forebrain ischemia at 3 time points (3h, 24h, and 48h) and at baseline. Total RNA was extracted from samples using Quick‐RNA™ MiniPrep kits (Zymo Research), and the expression of 423 miRNAs were analyzed using nCounter® miRNA expression panel (NanoString). Successful sub‐regional dissection was validated using RT‐qPCR detection of the DG‐rich gene desmoplakin.ResultsPronounced differences between CA1 and DG in miRNA expression was observed for several miRNAs, greatest with mir‐329, mir‐219‐2‐3p and mir‐181a, known regulators of ischemic injury. Relative levels of CA1 and DG miRNA expression were greatest in established brain‐enriched miRNAs, including mir‐124.ConclusionsMiRNA expression profiles in response to transient forebrain ischemia were assessed and compared between hippocampal sub‐regions for the first time. Observed differences in microRNA expression patterns between CA1 and DG may explain selective CA1 ischemic vulnerability. Targeted modulation of select miRNAs identified here may serve as a therapeutic intervention to improve cognition in survivors of cerebral ischemia.Support or Funding InformationSupported by Finnish Cultural Foundation award to Dr. Arvola and American Heart Association award 14FTF19970029 to Dr. Stary.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.