Transcriptomic Profiles from Stereo-EEGs May Reflect the Local Brain Cell Microenvironment in Human Epilepsy

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• Epilepsy pathomechanisms are increasingly understood via in-vivo human brain techniques.
• Stereo-electroencephalography (SEEG) electrodes can retain biomolecules and cells post-explantation.
• These retained materials offer potential for transcriptome and DNA methylation profiling.

Purpose of the Study:

• To analyze transcriptomes from SEEG electrodes to understand gene expression profiles.
• To determine the cellular and regional representation of recovered transcripts.
• To investigate the correlation between gene expression and local epileptiform activity.

Main Methods:

• Bioinformatic and RNA sequencing analyses were applied to explanted SEEG electrodes.
• Transcriptome data was analyzed for gene representation across cell types and brain structures.
• Correlation analyses were performed between gene expression and SEEG-recorded epileptiform activity.

Main Results:

• SEEG electrodes retained protein-coding transcripts reflecting the local molecular microenvironment and epileptiform activity.
• Consistent expression of housekeeping genes and neuronal activity markers was observed across patients and electrode sites.
• Transcripts represented diverse cell types (neurons, glia, endothelial cells) and brain regions, with some showing positional gradients.
• Gene expression patterns correlated with epileptiform activity detected by SEEG.

Conclusions:

• SEEG electrodes serve as valuable tools reflecting the molecular microenvironment of brain activity in epilepsy patients.
• This approach can identify molecular biomarkers and therapeutic targets for drug-resistant epilepsies.
• Potential applications exist for intraoperative surgical decision-making in epilepsy management.