Transcription of intermediate filament genes is enhanced in focal cortical dysplasia

Acta Neuropathol. 2001 Aug;102(2):141-8. doi: 10.1007/s004010000348.


Focal cortical dysplasia (FCD) is characterized by disorganized cerebral cortical cytoarchitecture. Increased expression of several intermediate filament (IF) proteins such as neurofilament, vimentin, alpha-internexin, and nestin observed in dysplastic "balloon" neurons (DN) may contribute to disrupted cortical lamination. We hypothesized that increased IF protein expression results from enhanced IF gene transcription within dysplastic neurons. We used a novel strategy to evaluate IF mRNA expression in three FCD specimens from medically intractable epilepsy patients. Poly(A) mRNA was amplified (aRNA) from single microdissected DN, morphologically normal neurons at the margin of the FCD resection, morphologically normal neurons in non-FCD cortex from epilepsy patients, and normal control neurons. Radiolabeled aRNA from single neurons was used to probe cDNA arrays containing the low (NFL), medium (NFM) and high (NFH) molecular weight neurofilament isoform, alpha-internexin, desmin, vimentin, peripherin (PRPH), nestin, and glial fibrillary acidic protein (GFAP) cDNAs. Hybridization intensity of aRNA-cDNA hybrids was used to quantify relative IF abundance. Increased expression of nestin, alpha-internexin, PRPH, vimentin, NFL, NFM, and NFH mRNAs was found in DN when compared with the three control neuronal subtypes. Desmin and GFAP mRNAs were not detected in any cell types. Expression of PRPH mRNA and protein in select DN was confirmed by reverse transcription-polymerase chain reaction and immunohistochemistry. We conclude that aberrant expression of IF proteins in FCD likely results from enhanced transcription of IF genes in dysplastic neurons and propose that future analysis of transcriptional elements that regulate IF expression be evaluated in FCD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Carrier Proteins / genetics
  • Cell Movement / genetics*
  • Cerebral Cortex / abnormalities*
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Desmin / genetics
  • Dissection / methods
  • Epilepsy / genetics*
  • Epilepsy / metabolism
  • Epilepsy / pathology
  • Female
  • Gene Expression Regulation, Developmental / physiology
  • Glial Fibrillary Acidic Protein / genetics
  • Humans
  • Intermediate Filament Proteins / genetics*
  • Intermediate Filament Proteins / metabolism
  • Membrane Glycoproteins*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nervous System Malformations / genetics*
  • Nervous System Malformations / metabolism
  • Nervous System Malformations / pathology
  • Nestin
  • Neurofilament Proteins / genetics
  • Neurofilament Proteins / metabolism
  • Neurons / metabolism*
  • Neurons / pathology
  • Oligonucleotide Array Sequence Analysis
  • Pathology / methods
  • Peripherins
  • RNA, Messenger / metabolism
  • Transcription, Genetic / genetics*
  • Vimentin / genetics


  • Carrier Proteins
  • Desmin
  • Glial Fibrillary Acidic Protein
  • Intermediate Filament Proteins
  • Membrane Glycoproteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nestin
  • Neurofilament Proteins
  • PRPH protein, human
  • Peripherins
  • RNA, Messenger
  • Vimentin
  • alpha-internexin
  • neurofilament protein L
  • neurofilament protein M