title: 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.
authors.affiliation: 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.
authors.forename: Mirna
authors.initials: M
authors.lastname: Lechpammer
authors.affiliation: 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.
authors.forename: Pia
authors.initials: P
authors.lastname: Wintermark
authors.affiliation: Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Merry
authors.affiliation: Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Michele C
authors.initials: MC
authors.lastname: Jackson
authors.affiliation: 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.
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Jantzie
authors.affiliation: Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Jensen
mesh_terms: D015153:Blotting, Western; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D058570:TOR Serine-Threonine Kinases; C497683:FMR1 protein, human; C546842:MTOR protein, human
keywords: autism; brain injury; fragile X mental retardation protein; hypoxia; mammalian target of rapamycin; prematurity