Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

Annals of Neurology
Mohit DubeyRogier Min

Abstract

Loss of function of the astrocyte-specific protein MLC1 leads to the childhood-onset leukodystrophy "megalencephalic leukoencephalopathy with subcortical cysts" (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole-cell patch-clamp recordings and K+ -sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of in...Continue Reading

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Citations

May 10, 2018·Brain Pathology·Rogier Min, Marjo S van der Knaap
Apr 18, 2018·Neurology·Eline M C HamiltonUNKNOWN MLC Research Group
May 7, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Angela SánchezAssumpció Bosch
Feb 17, 2021·Seizure : the Journal of the British Epilepsy Association·Valentina De GiorgisUNKNOWN Italian AGS Study Group
Feb 9, 2021·Frontiers in Cellular Neuroscience·Assumpció Bosch, Raúl Estévez
Sep 2, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Corinne S WilsonAlexander A Mongin
Jul 3, 2021·Nature Communications·Murat KirtayZhao-Qi Wang
Dec 9, 2021·Acta Neuropathologica·Marianna BugianiMarjo S van der Knaap

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