Dysregulation of FMRP/mTOR Signaling Cascade in Hypoxic-Ischemic Injury of Premature Human Brain

Mirna Lechpammer, Pia Wintermark, Katherine M. Merry, Michele C. Jackson, Lauren L. Jantzie, Frances E. Jensen

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

In this study the authors investigated whether dysregulation of the fragile X mental retardation protein and mammalian target of rapamycin signaling cascade can have a role in the pathogenesis of encephalopathy of prematurity following perinatal hypoxia-ischemia. The authors examined the brain tissue of newborns with encephalopathy and compared it to age-matched controls with normal brain development and adults. In normal controls, the fragile X mental retardation protein expression in cortical gray matter spiked 4-fold during 36-39 gestational weeks compared to the adult, with a concomitant suppression of p70S6K and S6. In encephalopathy cases, the developmental spike of fragile X mental retardation protein was not observed, and fragile X mental retardation protein levels remained significantly lower than in normal controls. Importantly, this fragile X mental retardation protein downregulation was followed by a significant overexpression of p70S6K and S6. These novel findings thus suggest that premature hypoxic-ischemic brain injury can affect the fragile X mental retardation protein/mammalian target of rapamycin pathway, as otherwise observed in inherited syndromes of cognitive disability and autism spectrum disorders.

Original languageEnglish (US)
Pages (from-to)426-432
Number of pages7
JournalJournal of Child Neurology
Volume31
Issue number4
DOIs
StatePublished - Mar 1 2016

Keywords

  • autism
  • brain injury
  • fragile X mental retardation protein
  • hypoxia
  • mammalian target of rapamycin
  • prematurity

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health

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