Hippocampal dysfunction and cognitive impairment in Fragile-X Syndrome

Crystal Bostrom, Suk Yu Yau, Namat Majaess, Mariana Vetrici, Joana Gil-Mohapel, Brian R. Christie

Research output: Journal article publicationReview articleAcademic researchpeer-review

34 Citations (Scopus)

Abstract

FXS is caused by transcriptional silencing of the Fragile X Mental Retardation 1 (Fmr1) gene due to a CGG repeat expansion, resulting in the loss of Fragile X Mental Retardation Protein (FMRP). FMRP is involved in transcriptional regulation and trafficking of mRNA from the nucleus to the cytoplasm and distal sites both in pre- and post-synaptic terminals. Consequently, FXS is a multifaceted disorder associated with impaired synaptic plasticity. One region of the brain that is significantly impacted by the loss of FMRP is the hippocampus, a structure that plays a critical role in the regulation of mood and cognition. This review provides an overview of the neuropathology of Fragile-X Syndrome, highlighting how structural and synaptic deficits in hippocampal subregions, including the CA1 exhibiting exaggerated metabotropic glutamate receptor dependent long-term depression and the dentate gyrus displaying hypofunction of N-methyl-D-aspartate receptors, contribute to cognitive impairments associated with this neurodevelopmental disorder.
Original languageEnglish
Pages (from-to)563-574
Number of pages12
JournalNeuroscience and Biobehavioral Reviews
Volume68
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • Fmr1 knock-out mice
  • Fragile-X Syndrome
  • Hippocampus
  • mGluR theory
  • NMDA receptor
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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