Correlation of transcriptome profile with electrical activity in temporal lobe epilepsy

Dominique Arion, Michael Sabatini, Travis Unger, Jesús Pastor, Lidia Alonso-Nanclares, Inmaculada Ballesteros-Yáñez, Rafael García Sola, Alberto Muñoz, Károly Mirnics, Javier DeFelipe

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

The biology underlying epileptic brain activity in humans is not well understood and likely depends on changes in gene expression. We performed a microarray transcriptome profiling of 12 anterolateral temporal cortical samples originating from five individuals who suffered with temporal lobe epilepsy for at least 10 years. Prior to partial lobectomy, intraoperative electrocorticography was performed on the cortical surface of each patient. These recordings showed characteristic differences in frequency and amplitude that were defined as "spiking" (abnormal) or "non-spiking" (normal). Between the transcriptome of the two sample groups, transferrin (TF) was the most differentially expressed gene. Furthermore, gene expression profiling also revealed a downregulation of multiple GABA system-related genes (GABRA5, GABRB3, ABAT) in the spiking samples and an upregulation of oligodendrocyte and lipid metabolism transcripts (MOG, CA2, CNP, SCD, PLP1, FA2H, ABCA2). In addition, several transcripts related to the classical MAPK cascade showed expression level alterations between the spiking and non-spiking samples (G3BP2, MAPK1, PRKAR1A, and MAP4K4). Out of 12 genes chosen for verification by RT qPCR, 9 showed significant expression changes in the microarray-predicted direction. Furthermore, the microarray and qPCR data were highly correlated (r = 0.98; P < 0.001). We conclude that abnormal electrical brain activity in the spiking samples is strongly correlated with gene expression changes and we speculate that some of the observed transcriptome changes may be directly involved in the induction or prevention of the ictal events seen in epilepsy.

Original languageEnglish (US)
Pages (from-to)374-387
Number of pages14
JournalNeurobiology of Disease
Volume22
Issue number2
DOIs
StatePublished - May 2006
Externally publishedYes

Keywords

  • DNA microarray
  • Ictal activity
  • Temporal epilepsy
  • Transcriptome
  • Transferrin
  • qPCR

ASJC Scopus subject areas

  • Neurology

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