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

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          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.

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          Author and article information

          Journal
          J. Child Neurol.
          Journal of child neurology
          SAGE Publications
          1708-8283
          0883-0738
          Mar 2016
          : 31
          : 4
          Affiliations
          [1 ] Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA Department of Pathology, Division of Neuropathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA mirna.lechpammer@ucdmc.ucdavis.edu.
          [2 ] Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA Department of Pediatrics, Division of Newborn Medicine, Montreal Children's Hospital, McGill University, Montréal, QC, Canada.
          [3 ] Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
          [4 ] Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA Department of Pediatrics, Office of Pediatric Research, University of New Mexico, Albuquerque, NM, USA.
          [5 ] Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
          Article
          0883073815596617 NIHMS704387
          10.1177/0883073815596617
          4740274
          26239490

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