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Expression of Circ_Satb1 Is Decreased in Mesial Temporal Lobe Epilepsy and Regulates Dendritic Spine Morphology

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  • Andreia Gomes-Duarte, Utrecht University
  • ,
  • Morten T. Venø, Omiics ApS
  • ,
  • Marina de Wit, Utrecht University
  • ,
  • Ketharini Senthilkumar, Utrecht University
  • ,
  • Mark H. Broekhoven, Utrecht University
  • ,
  • Joëlle van den Herik, Utrecht University
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  • Fleur R. Heeres, Utrecht University
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  • Daniëlle van Rossum, Utrecht University
  • ,
  • Mateja Rybiczka-Tesulov, Utrecht University
  • ,
  • Ivano Legnini, Helmholtz Association of German Research Centres
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  • Peter C. van Rijen, Utrecht University
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  • Pieter van Eijsden, Utrecht University
  • ,
  • Peter H. Gosselaar, Utrecht University
  • ,
  • Nikolaus Rajewsky, Helmholtz Association of German Research Centres
  • ,
  • Jørgen Kjems
  • Vamshidhar R. Vangoor, Utrecht University
  • ,
  • R. Jeroen Pasterkamp, Utrecht University

Mesial temporal lobe epilepsy (mTLE) is a chronic disease characterized by recurrent seizures that originate in the temporal lobes of the brain. Anti-epileptic drugs (AEDs) are the standard treatment for managing seizures in mTLE patients, but are frequently ineffective. Resective surgery is an option for some patients, but does not guarantee a postoperative seizure-free period. Therefore, further insight is needed into the pathogenesis of mTLE to enable the design of new therapeutic strategies. Circular RNAs (circRNAs) have been identified as important regulators of neuronal function and have been implicated in epilepsy. However, the mechanisms through which circRNAs contribute to epileptogenesis remain unknown. Here, we determine the circRNA transcriptome of the hippocampus and cortex of mTLE patients by using RNA-seq. We report 333 differentially expressed (DE) circRNAs between healthy individuals and mTLE patients, of which 23 circRNAs displayed significant adjusted p-values following multiple testing correction. Interestingly, hippocampal expression of circ_Satb1, a circRNA derived from special AT-rich sequence binding protein 1 (SATB1), is decreased in both mTLE patients and in experimental epilepsy. Our work shows that circ_Satb1 displays dynamic patterns of neuronal expression in vitro and in vivo. Further, circ_Satb1-specific knockdown using CRISPR/CasRx approaches in hippocampal cultures leads to defects in dendritic spine morphology, a cellular hallmark of mTLE. Overall, our results identify a novel epilepsy-associated circRNA with disease-specific expression and previously unidentified cellular effects that are relevant for epileptogenesis.

Original languageEnglish
Article number832133
JournalFrontiers in Molecular Neuroscience
Publication statusPublished - Mar 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Gomes-Duarte, Venø, de Wit, Senthilkumar, Broekhoven, van den Herik, Heeres, van Rossum, Rybiczka-Tesulov, Legnini, van Rijen, van Eijsden, Gosselaar, Rajewsky, Kjems, Vangoor and Pasterkamp.

    Research areas

  • circular RNA, dendritic spine, epilepsy, hippocampus, RNA-sequencing

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