Related Experiment Videos
Analysis of neocortex in three males with the fragile X syndrome
V J Hinton1, W T Brown, K Wisniewski
1Queens College, City University of New York, New York.
Abstract:
Fragile X [fraX] syndrome is a common hereditary disorder associated with a fragile site marker at Xq27.3 which clinically presents as a form of mental retardation (MR). Postmortem investigation of 3 fraX positive males with mild to moderate MR did not document any gross neuropathological changes. Golgi analysis of neocortical dendritic spine morphology extended our previous observations of immature, long, tortuous spines in one adult case of fraX (Rudelli, et al., Acta Neuropathologica 67:289-295, 1985) to 2 new cases. Evidence for similar dendritic spine abnormalities was found, although Golgi analysis was less than optimal because of incomplete dendritic stain impregnation. Neocortical intra-layer cell density was also investigated in all 3 cases. Cresyl violet stained neurons were counted in 10 randomly selected fields in neocortical layers II-VI of cingulate and temporal association areas (Brodmann's areas 23 and 38). Neuron counts in fraX and control neocortex showed no significant differences. Thus, abnormal dendritic spine morphology with preservation of neuronal density appears to characterize the neocortex in individuals with this common form of mental retardation.
Insights
Fragile X syndrome, a genetic disorder causing intellectual disability, is characterized by abnormal neocortical dendritic spine morphology. Neuronal density remains unaffected in affected individuals.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Fragile X (fraX) syndrome is a hereditary disorder linked to Xq27.3, presenting as mental retardation.
- Previous studies suggested neuropathological changes, but gross examination revealed none in mild to moderate cases.
Observation:
- Postmortem Golgi analysis of 3 fraX males revealed immature, long, and tortuous neocortical dendritic spines.
- Similar abnormalities were observed in 2 new cases, though staining was suboptimal.
- Neocortical neuron density was assessed in layers II-VI of cingulate and temporal association areas.
Findings:
- Abnormal dendritic spine morphology is a consistent feature in the neocortex of individuals with Fragile X syndrome.
- No significant differences in neuron counts were found between fraX and control neocortex.
- Preserved neuronal density alongside abnormal spine morphology characterizes the fraX neocortex.
Implications:
- These findings highlight specific neuropathological alterations at the dendritic level in Fragile X syndrome.
- Understanding these microstructural changes can inform future research into the mechanisms of intellectual disability.
- This study contributes to the neuropathological characterization of a common genetic cause of mental retardation.