title: Whole Transcriptome Screening Reveals Myelination Deficits in Dysplastic Human Temporal Neocortex.
abstract: Focal cortical dysplasias (FCDs) are local malformations of the human neocortex with strong epileptogenic potential. To investigate the underlying pathomechanisms, we performed a whole human transcriptome screening to compare the gene expression pattern of dysplastic versus nondysplastic temporal neocortex. Tissue obtained from FCD IIIa cases (mean age 20.5 years) who had undergone surgical treatment, due to intractable epilepsy, was compared with nondysplastic specimens (mean age 19.9 years) by means of Affymetrix arrays covering 28 869 genes. We found 211 differentially expressed genes (DEX) among which mainly genes important for oligodendrocyte differentiation and myelination were downregulated in FCD IIIa. These findings were confirmed as functionally important by Database for Annotation, Visualization, and Integrated Discovery (DAVID) analysis. The reduced expression of myelin-associated transcripts was confirmed for FCD Ia, IIa, and IIIa by real-time RT-qPCR. In addition, we found that the density of myelin basic protein mRNA-expressing oligodendrocytes and of 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive myelin fibers was significantly reduced in dysplastic cortex. Moreover, high-resolution confocal imaging and 3D reconstruction revealed that the myelin fiber network was severely disorganized in dysplastic neocortex, indicating a disturbance of myelin sheath formation and maintenance in FCD.
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery.|Faculty of Biology.
authors.forename: Catharina
authors.initials: C
authors.lastname: Donkels
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery.|Faculty of Biology.
authors.forename: Philipp
authors.initials: P
authors.lastname: Janz
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery.
authors.forename: Susanne
authors.initials: S
authors.lastname: Huber
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery.|Department of Neurosurgery.
authors.forename: Julia
authors.initials: J
authors.lastname: Nakagawa
authors.affiliation: Institute of Neuropathology.|Center for Biological Signalling Studies.
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.affiliation: Epilepsy Center Freiburg, University Medical Center Freiburg, Freiburg, Germany.|BrainLinks-BrainTools, University of Freiburg, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze-Bonhage
authors.affiliation: Department of Neurosurgery.
authors.forename: Astrid
authors.initials: A
authors.lastname: Weyerbrock
authors.affiliation: Department of Neurosurgery.
authors.forename: Josef
authors.initials: J
authors.lastname: Zentner
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery.|Bernstein Center Freiburg.|BrainLinks-BrainTools, University of Freiburg, Freiburg, Germany.
authors.forename: Carola A
authors.initials: CA
authors.lastname: Haas
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054220:Malformations of Cortical Development / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D019579:Neocortex / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D059467:Transcriptome / Q000502:physiology*; D055815:Young Adult
chemical_list: C499048:MBP protein, human; D004676:Myelin Basic Protein
keywords: brain malformation; development; epilepsy; microarray; oligodendrocyte