Altered axon initial segment in hippocampal newborn neurons, associated with recurrence of temporal lobe epilepsy in rats

Mol Med Rep. 2017 Sep;16(3):3169-3178. doi: 10.3892/mmr.2017.7017. Epub 2017 Jul 15.

Abstract

Hippocampal neurogenesis in temporal lobe epilepsy (TLE) may result in alteration of the excitability of neurons, which contributes to spontaneous recurrent seizures. Axon initial segment (AIS) structural and functional plasticity is important in the control of neuronal excitability. It remains to be elucidated whether the plasticity of AIS occurs in hippocampal newly‑generated neurons that are involved in recurrent seizures following pilocarpine‑induced status epilepticus (SE). The present study first established a pilocarpine‑induced TLE rat model to assess the features of newborn neurons and AIS plasticity alterations using double immunofluorescence staining of Ankyrin G and doublecortin (DCX). AIS plasticity alterations include length and distance from soma in the hippocampal newly‑generated neurons post‑SE. The results of the present study demonstrated that pilocarpine‑induced epileptic rats exhibited aberrant hippocampal neurogenesis and longer DCX‑labeled cell dendrites in the dentate gyrus. Pilocarpine‑induced epileptic rats demonstrated shortened lengths of AIS and an increased distance from the soma in hippocampal newborn neurons. Mibefradil, a T/L‑type calcium blocker, reversed the alterations in length and position of AIS in hippocampal newborn neurons post‑SE, accompanied by decreased long‑term seizure activity without increased aberrant neurogenesis. These findings indicate that the plasticity of AIS in hippocampal neurogenesis may have profound consequences in epilepsy, at least in animals.

MeSH terms

  • Animals
  • Axon Initial Segment / drug effects
  • Axon Initial Segment / pathology*
  • Behavior, Animal / drug effects
  • Cell Proliferation / drug effects
  • Chronic Disease
  • Dendrites / drug effects
  • Dendrites / pathology
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / pathology
  • Doublecortin Protein
  • Electroencephalography
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / drug therapy
  • Epilepsy, Temporal Lobe / pathology*
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • Male
  • Mibefradil / pharmacology
  • Mibefradil / therapeutic use
  • Neurogenesis* / drug effects
  • Pilocarpine
  • Rats, Sprague-Dawley
  • Recurrence

Substances

  • Dcx protein, rat
  • Doublecortin Protein
  • Pilocarpine
  • Mibefradil