Dendritic spine structural anomalies in fragile-X mental retardation syndrome

Cereb Cortex. 2000 Oct;10(10):1038-44. doi: 10.1093/cercor/10.10.1038.


Fragile-X syndrome is the most common single-gene inherited form of mental retardation. Morphological studies suggest a possible failure of the synapse maturation process. Cerebral cortical spine morphology in fragile-X syndrome and in a knockout mouse model of it appears immature, with long, thin spines much more common than the stubby and mushroom-shaped spines more characteristic of normal development. In human fragile-X syndrome there is also a higher density of spines along dendrites, suggesting a possible failure of synapse elimination. While variously misshapen spines are characteristic of a number of mental retardation syndromes, the overabundance of spines seen in fragile-X syndrome is unusual. Taken with evidence of neurotransmitter activation of the synthesis of the fragile-X protein (FMRP) at synapses in vitro and evidence for behaviorally induced FMRP expression in vivo, and with evidence compatible with a role for FMRP in regulating the synthesis of other proteins, it is possible that FMRP serves as an 'immediate early protein' at the synapse that orchestrates aspects of synaptic development and plasticity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Brain / pathology
  • Dendrites / ultrastructure*
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / complications*
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology*
  • Nerve Tissue Proteins / physiology
  • RNA-Binding Proteins*
  • Synapses / physiology


  • FMR1 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein