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Calm in the chaos: Targeting mTOR to reduce glioma-driven neuronal hyperexcitability

Matthia A Karreman1, Varun Venkataramani1

  • 1Neurology Clinic and European Center for Neurooncology (EZN), University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Neuron
|March 20, 2025
PubMed

Insights

Primary brain tumors cause seizures by altering neurons. mTOR inhibition rapidly reverses these tumor-induced neuronal changes in a mouse model, offering potential therapeutic strategies for epilepsy.

Area of Science:

  • Neuroscience
  • Oncology
  • Epileptology

Background:

  • Primary brain tumors are known to induce neuronal hyperexcitability.
  • This hyperexcitability is a primary cause of epileptic seizures in patients.

Purpose of the Study:

  • To investigate the specific alterations in excitatory tumor-associated neurons.
  • To determine if mTOR inhibition can reverse these tumor-induced neuronal changes.

Main Methods:

  • Utilized a mouse model of primary brain tumors.
  • Performed genetic, structural, and functional analyses of neurons.
  • Assessed the effects of mTOR inhibition on these neurons.

Main Results:

  • Demonstrated specific genetic, structural, and functional alterations in excitatory tumor-associated neurons.
  • Showcased that mTOR inhibition rapidly reverses these identified neuronal alterations.

Conclusions:

  • Tumor-associated neurons exhibit significant changes contributing to hyperexcitability and seizures.
  • mTOR inhibition presents a promising rapid therapeutic approach for managing seizures associated with brain tumors.

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