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

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.

journal_name

J Child Neurol

authors

Lechpammer M,Wintermark P,Merry KM,Jackson MC,Jantzie LL,Jensen FE

doi

10.1177/0883073815596617

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

426-32

issue

4

eissn

0883-0738

issn

1708-8283

pii

0883073815596617

journal_volume

31

pub_type

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