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Anteromesial Temporal Lobectomy for Medically Intractable Temporal Lobe Epilepsy: An Operative Study
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Anteromesial Temporal Lobectomy for Medically Intractable Temporal Lobe Epilepsy: An Operative Study

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Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to

Richard G Sánchez1, R Ryley Parrish2, Megan Rich1

  • 1Department of Neurobiology, University of Alabama, Birmingham, AL, United States.

Neurobiology of Disease
|January 10, 2019
PubMed

Insights

Temporal Lobe Epilepsy (TLE) involves altered protein modifications. Inhibiting O-GlcNAcase (OGA) restored O-GlcNAc levels and reduced seizure activity, suggesting OGA as a therapeutic target for TLE.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Epilepsy Research

Background:

  • Temporal Lobe Epilepsy (TLE) is linked to protein changes and post-translational modifications (PTMs).
  • O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM tied to metabolic substrates, regulated by O-GlcNAc transferase (OGT) and O-GlcNAc glycosidase (OGA).

Purpose of the Study:

  • To investigate OGT/OGA and O-GlcNAc levels in the epileptic hippocampus.
  • To determine if manipulating OGT/OGA and O-GlcNAc affects epileptiform activity.

Main Methods:

  • Utilized the kainate rat model of TLE and human TLE hippocampal tissue.
  • Assessed global and protein-specific O-GlcNAcylation and OGT expression.
  • Administered OGA inhibitor Thiamet-G to evaluate its effects on O-GlcNAcylation and seizure activity.

Main Results:

  • Reduced O-GlcNAc levels and OGT expression were observed in both the kainate model and human TLE hippocampus.
  • Inhibition of OGA with Thiamet-G increased O-GlcNAc levels.
  • Thiamet-G treatment decreased seizure duration and epileptic spike frequency.

Conclusions:

  • Loss of O-GlcNAc homeostasis is implicated in TLE.
  • Targeting OGA can restore O-GlcNAc homeostasis and potentially control seizures in TLE.
  • OGA inhibition presents a potential therapeutic strategy for TLE seizure management.
Keywords:
ElectroencephalogramElectrophysiologyHippocampusMagnetic resonance imagingMass spectrometryO-GlcNAcylationPost-translational modificationThiamet-G

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