Whole Transcriptome Screening Reveals Myelination Deficits in Dysplastic Human Temporal Neocortex
Catharina Donkels1,2, Dietmar Pfeifer3, Philipp Janz1,2
1Experimental Epilepsy Research, Department of Neurosurgery.
Cerebral Cortex (New York, N.Y. : 1991)
|January 23, 2016
Summary
Focal cortical dysplasias (FCDs) show altered gene expression, particularly reduced myelin-related genes. This suggests impaired oligodendrocyte differentiation and myelination contribute to FCD pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Focal cortical dysplasias (FCDs) are malformations of the human neocortex.
- FCDs possess significant epileptogenic potential, driving research into their underlying mechanisms.
Purpose of the Study:
- To investigate the pathomechanisms of FCDs.
- To compare gene expression patterns in dysplastic versus nondysplastic temporal neocortex.
Main Methods:
- Whole human transcriptome screening using Affymetrix arrays.
- Differential gene expression analysis identified 211 differentially expressed genes (DEX).
- Real-time RT-qPCR, confocal imaging, and 3D reconstruction validated findings.
Main Results:
- Genes crucial for oligodendrocyte differentiation and myelination were downregulated in FCD IIIa.
- Reduced expression of myelin-associated transcripts confirmed across FCD subtypes (Ia, IIa, IIIa).
- Significant reduction in myelin basic protein mRNA-expressing oligodendrocytes and myelin fibers observed in dysplastic cortex.
Conclusions:
- Dysplastic neocortex in FCDs exhibits disturbed myelin sheath formation and maintenance.
- Impaired oligodendrocyte differentiation and myelination are key pathomechanisms in FCDs.
- Findings highlight the role of myelin abnormalities in FCD pathogenesis and epilepsy.
