GAS5 silencing protects against hypoxia/ischemia-induced neonatal brain injury

Biochem Biophys Res Commun. 2018 Feb 26;497(1):285-291. doi: 10.1016/j.bbrc.2018.02.070. Epub 2018 Feb 8.

Abstract

Hypoxic/ischemic brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. However, the molecular mechanism of HIBD in the neonatal infant is still elusive. Long non-coding RNAs are shown as important regulators of brain development and many neurological diseases. Here, we determined the role of long noncoding RNA-GAS5 in HIBD. GAS5 expression was significantly up-regulated in hypoxic/ischemic-injured neonatal brain and hippocampal neurons. GAS5 silencing protected against hypoxic/ischemic-induced brain injury in vivo and primary hippocampal neuron injury in vitro. Mechanistically, GAS5 regulated hippocampal neuron function by sponging miR-23a. Intracerebroventricular injection of GAS5 shRNA significantly decreased brain GAS5 expression, reduced brain infarct size, and improved neurological function recovery. Collectively, this study suggests a promising therapeutic approach of GAS5 inhibition in the treatment of neonatal HIBD.

Keywords: Brain damage; Long noncoding RNA; Therapeutic approach; microRNA sponge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Gene Silencing
  • Genetic Therapy / methods*
  • Hippocampus / pathology*
  • Hippocampus / physiopathology*
  • Hypoxia-Ischemia, Brain / physiopathology*
  • Hypoxia-Ischemia, Brain / therapy*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome

Substances

  • RNA, Long Noncoding
  • long non-coding RNA GAS5, mouse