Differential subregional hippocampal expression patterns of microRNA‐338 and downstream target INSM1 following global cerebral ischemia.

Abstract

Cognitive dysfunction remains a devastating outcome in survivors of cardiac arrest. The principle source of cognitive impairment is attributed to delayed death of hippocampal cornu ammonis 1 (CA1) neurons following blood loss to the brain. Treatments that directly target CA1 neurons have not had translational clinical success. Astrocytes regulate the survival of CA1 neurons following injury, and treatments targeting astrocytes have been effective in protection from global cerebral ischemia. MicroRNAs (miRs) are non‐coding RNAs that regulate gene expression at the post‐transcriptional level, and modulation of miRs have been shown to augment survivability of hippocampal astrocytes. We identified miR‐338, a known modulator of astrocyte function, as a potential regulator of the transcriptional repressor INSM1, a critical epigenetic regulator of cell fate. To test the hypothesis that miR‐338 regulates astrocyte‐mediated neuronal survival following global cerebral ischemia by targeting INSM1, we assessed hippocampal subregional expression patterns of INSM1 and miR‐338 following global cerebral ischemia. We observed that prior to injury, INSM1 is highly expressed in the ischemia‐resistant dentate gyrus relative to the ischemia‐sensitive CA1. Following global cerebral ischemia, expression of INSM1 in the CA1 progressively increased, equaling DG expression after 7 days. We confirmed that increased expression in the CA1 was localized to astrocytes. Immediate future experiments will assess CA1 survivability and cognitive behavioral outcomes following miR‐338 inhibition in vivo.Support or Funding InformationRona Giffard NIH #5R01NS053898, Creed Stary AHA #14FTF19970029This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.