ePoster

Unraveling the molecular mechanisms of epilepsy in pediatric patients with tuberous sclerosis complex (TSC)

Frederik Nørby Friis Sørensen, Mirte Scheper, Rasmus Rydbirk, James D. Mills, Irina Korshunova, Eleonora Aronica, Konstantin Khodosevich
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Frederik Nørby Friis Sørensen, Mirte Scheper, Rasmus Rydbirk, James D. Mills, Irina Korshunova, Eleonora Aronica, Konstantin Khodosevich

Abstract

Tuberous sclerosis complex (TSC) is a genetic disorder where many patients affected by the disease suffer from refractive epilepsy. To alleviate related symptoms, the patients must undergo surgery to resect the epileptogenic lesion. Obtaining this tissue and instantly flash freeze it provides a unique opportunity to gain insight to the pathogenesis of TSC.Thus, we embarked on an in-depth unbiased characterization of the transcriptomic landscape, cellular identify, and potential epileptogenic networks of frontal cortical tubers of pediatric TSC using snRNA-seq on resected epileptic tissue and comparing to sex and aged matched controls.Strikingly, we revealed that despite a highly disorganized cortical layer structure, virtually all layer-specific neuron types are present in cortical tubers, even rare subtypes. While the cell type specific defining molecular patterns being maintained in TSC, the general transcriptomic landscape is highly shifted in cortical tubers.Lastly, using a fluorescent in-situ hybridization approach we validated layer wise neuronal molecular patterns and compositional changes that occur in frontal cortical tubers of tuberous sclerosis.Thus, in this study we demonstrate that despite the highly disorganized cortical structure of TSC, all neuronal identities, which are present in the neurotypical cortex, are also present in TSC. This in turn reveals tremendous potential translational opportunities where modulation of neuronal migration could potentially recover circuit structure and ultimately lead to functional recovery and seizure amelioration.

Unique ID: fens-24/unraveling-molecular-mechanisms-epilepsy-f236b14e