Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7302955 | Neuroscience & Biobehavioral Reviews | 2016 | 41 Pages |
Abstract
Fragile-X Syndrome (FXS) is the most common form of inherited intellectual disability and the leading genetic cause of autism spectrum disorder. 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.
Keywords
EPSCsmGluRFXSGSK3βDHPGFmr1FMRPS6K1CaMKIIAMPARCGGL-LTPMWMfragile X mental retardation 1TBSPCNANMDAR(S)-3,5-dihydroxyphenylglycine5-bromo-2′-deoxyuridineNMDA receptorp70 ribosomal S6 kinaseα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptorProliferating Cell Nuclear AntigenAutism spectrum disorderγ-aminobutyric acidlong-term depressionMRIcornu ammonisBrdUintelligence quotientTheta-burst stimulationMagnetic resonance imaginglong-term potentiationLTPexcitatory postsynaptic currentsFragile-X syndromedentate gyrusMorris water mazeLTDknock-outASDHippocampusfragile X mental retardation proteincalcium/calmodulin-dependent protein kinase IISynaptic plasticityGABAGlycogen synthase kinase 3βN-methyl-d-aspartate receptorMetabotropic glutamate receptor
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Authors
Crystal Bostrom, Suk-yu Yau, Namat Majaess, Mariana Vetrici, Joana Gil-Mohapel, Brian R. Christie,