Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: A quantitative examination

• Published in: American journal of medical genetics 2001-01, Vol.98 (2), p.161-167
• Main Authors: Irwin, Scott A., Patel, Biraju, Idupulapati, Madhuri, Harris, Jennifer B., Crisostomo, Ralph A., Larsen, Brian P., Kooy, Frank, Willems, Patrick J., Cras, Patrick, Kozlowski, Piotr B., Swain, Rodney A., Weiler, Ivan Jeanne, Greenough, William T.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Dendrites - pathology; dendritic spines; Fragile X Syndrome - pathology; fragile-X syndrome; Golgi; human; Humans; Intellectual Disability - pathology; Male; Medical genetics; Medical sciences; mental retardation; Middle Aged; neuropathology; synaptic plasticity; Temporal Lobe - pathology; Visual Cortex - pathology
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/1096-8628(20010115)98:2<161::AID-AJMG1025>3.0.CO;2-B

Fragile‐X syndrome is a common form of mental retardation resulting from the inability to produce the fragile‐X mental retardation protein. Qualitative examination of human brain autopsy material has shown that fragile‐X patients exhibit abnormal dendritic spine lengths and shapes on parieto‐occipital neocortical pyramidal cells. Similar quantitative results have been obtained in fragile‐X knockout mice, that have been engineered to lack the fragile‐X mental retardation protein. Dendritic spines on layer V pyramidal cells of human temporal and visual cortices stained using the Golgi‐Kopsch method were investigated. Quantitative analysis of dendritic spine length, morphology, and number was carried out on patients with fragile‐X syndrome and normal age‐matched controls. Fragile‐X patients exhibited significantly more long dendritic spines and fewer short dendritic spines than did control subjects in both temporal and visual cortical areas. Similarly, fragile‐X patients exhibited significantly more dendritic spines with an immature morphology and fewer with a more mature type morphology in both cortical areas. In addition, fragile‐X patients had a higher density of dendritic spines than did controls on distal segments of apical and basilar dendrites in both cortical areas. Long dendritic spines with immature morphologies and elevated spine numbers are characteristic of early development or a lack of sensory experience. The fact that these characteristics are found in fragile‐X patients throughout multiple cortical areas may suggest a global failure of normal dendritic spine maturation and or pruning during development that persists throughout adulthood. © 2001 Wiley‐Liss, Inc.