Correlation of transcriptome profile with electrical activity in temporal lobe epilepsy.
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.
Department of Psychiatry and Neurobiology, University of Pittsburgh, School of Medicine, School of Medicine, W1655 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Dominique
D
Arion
Michael
M
Sabatini
Travis
T
Unger
Jesús
J
Pastor
Lidia
L
Alonso-Nanclares
Inmaculada
I
Ballesteros-Yáñez
Rafael
R
García Sola
Alberto
A
Muñoz
Károly
K
Mirnics
Javier
J
DeFelipe
D000200:Action Potentials / Q000235:genetics; D000328:Adult; D015536:Down-Regulation / Q000235:genetics; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D005680:gamma-Aminobutyric Acid