Dysregulated Ca2+-Permeable AMPA Receptor Signaling in Neural Progenitors Modeling Fragile X Syndrome

Claudia Elisabetta Danesi, Kari Pekka Keinänen, Maija Liisa Castren

Research output: Contribution to journalReview ArticleScientificpeer-review

Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder that represents a common cause of intellectual disability and is a variant of autism spectrum disorder (ASD). Studies that have searched for similarities in syndromic and non-syndromic forms of ASD have paid special attention to alterations of maturation and function of glutamatergic synapses. Copy number variations (CNVs) in the loci containing genes encoding alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) subunits are associated with ASD in genetic studies. In FXS, dysregulated AMPAR subunit expression and trafficking affect neural progenitor differentiation and synapse formation and neuronal plasticity in the mature brain. Decreased expression of GluA2, the AMPAR subunit that critically controls Ca2+-permeability, and a concomitant increase in Ca2+-permeable AMPARs (CP-AMPARs) in human and mouse FXS neural progenitors parallels changes in expression of GluA2-targeting microRNAs (miRNAs). Thus, posttranscriptional regulation of GluA2 by miRNAs and subsequent alterations in calcium signaling may contribute to abnormal synaptic function in FXS and, by implication, in some forms of ASD.

Original languageEnglish
Article number2
JournalFrontiers in Synaptic Neuroscience
Volume11
Number of pages8
ISSN1663-3563
DOIs
Publication statusPublished - 8 Feb 2019
MoE publication typeA2 Review article in a scientific journal

Fields of Science

  • AMPA
  • AUTISM SPECTRUM DISORDERS
  • DIFFERENTIATION
  • EXPRESSION
  • FMRP
  • GENE
  • GLUTAMATE RECEPTORS
  • GluA2
  • MENTAL-RETARDATION PROTEIN
  • MOUSE MODEL
  • SILENT SYNAPSES
  • SYNAPTIC PLASTICITY
  • autism
  • fragile X syndrome
  • miR-181
  • miRNA
  • neural progenitor
  • plasticity
  • 3112 Neurosciences

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