Dendritic spine structural anomalies in fragile-X mental retardation syndrome

Fragile-X syndrome is the most common single-gene inherited form of mental retardation. Morphological studies suggest a possible failure of the synaps e maturation process. Cerebral cortical spine morphology in fragile-X syndr ome and in a knockout mouse model of it appears immature, with long, thin s pines much more common than the stubby and mushroom-shaped spines more char acteristic 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 s een in fragile-X syndrome is unusual. Taken with evidence of neurotransmitt er 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 p rotein' at the synapse that orchestrates aspects of synaptic development an d plasticity.