Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?

Mauro DiNuzzo, Silvia Mangia, Bruno Maraviglia, Federico Giove

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Epilepsy is a family of brain disorders with a largely unknown etiology and high percentage of pharmacoresistance. The clinical manifestations of epilepsy are seizures, which originate from aberrant neuronal synchronization and hyperexcitability. Reactive astrocytosis, a hallmark of the epileptic tissue, develops into loss-of-function of glutamine synthetase, impairment of glutamate-glutamine cycle and increase in extracellular and astrocytic glutamate concentration. Here, we argue that chronically elevated intracellular glutamate level in astrocytes is instrumental to alterations in the metabolism of glycogen and leads to the synthesis of polyglucosans. Unaccessibility of glycogen-degrading enzymes to these insoluble molecules compromises the glycogenolysis-dependent reuptake of extracellular K+ by astrocytes, thereby leading to increased extracellular K+ and associated membrane depolarization. Based on current knowledge, we propose that the deterioration in structural homogeneity of glycogen particles is relevant to disruption of brain K+ homeostasis and increased susceptibility to seizures in epilepsy.

Original languageEnglish (US)
Pages (from-to)307-316
Number of pages10
JournalMetabolic Brain Disease
Volume30
Issue number1
DOIs
StatePublished - Feb 1 2015
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments The author S.M. thanks the grant KL2 RR033182 from the National Insititute of Health (NIH) to the University of Minnesota Clinical and Translational Science Institute (CTSI) for support.

Funding Information:
The author S.M. thanks the grant KL2 RR033182 from the National Insititute of Health (NIH) to the University of Minnesota Clinical and Translational Science Institute (CTSI) for support.

Keywords

  • Astrocytes
  • Epilepsy
  • Glutamate
  • Glycogen
  • Potassium

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