Correlation of transcriptome profile with electrical activity in temporal lobe epilepsy

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Epilepsy pathogenesis is poorly understood, with gene expression changes suspected.
• Temporal lobe epilepsy (TLE) involves abnormal brain electrical activity.

Purpose of the Study:

• To investigate gene expression differences in TLE patients with and without abnormal brain activity.
• To identify molecular pathways associated with epileptic brain activity.

Main Methods:

• Microarray transcriptome profiling of temporal cortical samples from TLE patients.
• Intraoperative electrocorticography to classify samples as spiking (abnormal) or non-spiking (normal).
• RT qPCR validation of microarray findings.

Main Results:

• Transferrin (TF) was the most differentially expressed gene.
• Downregulation of GABA system genes (GABRA5, GABRB3, ABAT) and upregulation of oligodendrocyte/lipid metabolism genes (MOG, CA2, CNP, SCD, PLP1, FA2H, ABCA2) in spiking samples.
• Alterations in MAPK cascade transcripts (G3BP2, MAPK1, PRKAR1A, MAP4K4) were observed.

Conclusions:

• Abnormal electrical brain activity in TLE is strongly correlated with specific gene expression changes.
• Identified gene expression alterations may play a role in the induction or prevention of epileptic seizures.