Dexamethasone ameliorates the damage of hippocampal filamentous actin cytoskeleton but is not sufficient to cease epileptogenesis in pilocarpine induced epileptic mice

Epilepsy Res. 2019 Aug:154:26-33. doi: 10.1016/j.eplepsyres.2019.04.009. Epub 2019 Apr 18.

Abstract

Rogressive deconstruction of filament actin (F-actin) in hippocampal neurons in the epileptic brain have been associated with epileptogenesis. Previous clinical studies suggest that glucocorticoids treatment plays beneficial roles in refractory epilepsy. Glucocorticoids treatment affects dendritic spine morphology by regulating local glucocorticoid receptors and F-actin cytoskeleton dynamics. However, how glucocorticoids regulate epileptogenesis by controlling F-actin cytoskeleton is not clear yet. Here we study the function of glucocorticoids in epileptogenesis by examining F-actin abundance, hippocampal neuron number, and synaptic markers in pilocarpine-induced epileptic mice in the presence or absence of dexamethasone (DEX) treatment. We found that spontaneous seizure duration was significantly reduced; F-actin damage in hippocampal subfields was remarkably attenuated; loss of pyramidal cells was dramatically decreased; more intact synaptic structures indicated by pre- and postsynaptic markers were preserved in multiple hippocampal regions after DEX treatment. However, the number of ZNT3 positive particles in the molecular layer in the hippocampus of pilocarpine epileptic mice was not altered after DEX treatment. Although not sufficient to cease epileptogenesis, our results suggest that dexamethasone treatment ameliorates the damage of epileptic brain by stabilizing F-actin cytoskeleton in the pilocarpine epileptic mice.

Keywords: Dexamethasone; Epilepsy; Filamentous actin; Glucocorticoids; Pilocarpine; Spontaneous seizures; Synapse maintenance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / metabolism*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use*
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy
  • Epilepsy / metabolism*
  • Hippocampus / chemistry
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Pilocarpine / toxicity*

Substances

  • Anti-Inflammatory Agents
  • Pilocarpine
  • Dexamethasone