Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency

Mol Cell Neurosci. 2002 Feb;19(2):138-51. doi: 10.1006/mcne.2001.1085.

Abstract

Lack of expression of the fragile X mental retardation protein (FMRP), due to silencing of the FMR1 gene, causes the Fragile X syndrome. Although FMRP was characterized previously to be an RNA binding protein, little is known about its function or the mechanisms underlying the Fragile X syndrome. Here we report that the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit, GluR1, was decreased in the cortical synapses, but not in the hippocampus or cerebellum, of FMR1 gene knockout mice. Reduced long-term potentiation (LTP) was also found in the cortex but not in the hippocampus. Another RNA binding protein, FXR; the N-methyl-D-aspartate receptor subunit, NR2; and other learning-related proteins including c-fos, synapsin, myelin proteolipid protein, and cAMP response element binding protein were not different between FMR1 gene knockout and wild-type mice. These findings suggest that the depressed cortical GluR1 expression and LTP associated with FMRP deficiency could contribute to the Fragile X phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / physiopathology
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Down-Regulation / genetics*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism*
  • Fragile X Syndrome / pathology
  • Gene Expression Regulation / genetics
  • Learning Disabilities / genetics
  • Learning Disabilities / metabolism
  • Learning Disabilities / physiopathology
  • Liver / metabolism
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / genetics*
  • Male
  • Mice
  • Mice, Knockout
  • Myelin Proteolipid Protein / metabolism
  • Myocardium / metabolism
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synapsins / metabolism
  • Synaptic Membranes / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics*
  • Tetrodotoxin / pharmacology

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Excitatory Amino Acid Antagonists
  • FXR1 protein, human
  • Fmr1 protein, mouse
  • Myelin Proteolipid Protein
  • NR2A NMDA receptor
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Synapsins
  • Fragile X Mental Retardation Protein
  • Tetrodotoxin
  • glutamate receptor ionotropic, AMPA 1