Upregulated dynamin 1 in an acute seizure model and in epileptic patients

Synapse. 2015 Feb;69(2):67-77. doi: 10.1002/syn.21788. Epub 2014 Nov 11.

Abstract

Dynamin 1 is a neuron-specific guanosine triphosphatase (GTPase) that is an essential component of membrane fission during synaptic vesicle recycling and endocytosis. This study evaluated the dynamin 1 expression pattern in the acute lithium-pilocarpine rat model and in patients with temporal lobe epilepsy (TLE) and investigated whether altering the dynamin 1 expression pattern affects epileptic seizures in vivo and in vitro. The immunofluorescence, western blot analysis, and reverse transcription-PCR results show that the dynamin 1 expression level increased significantly in experimental rats from day 1 to day 7 after the onset of seizures and was significantly higher in TLE patients. The behavioral study revealed that inhibiting dynamin 1 increased the latency time of the first seizure and decreased the frequency and severity of the seizures. In addition, electrophysiological recordings from brain slices showed that inhibiting dynamin 1 reduces the frequency of Mg-free induced seizure-like activity. The anticonvulsant effect of dynasore was more effective at 10 µM than at 1 µM or 160 µM. These results indicate that the altered level of dynamin 1 may contribute to the development of epileptic seizures and that the targeted regulation of dynamin 1 activity may control epileptic seizures.

Keywords: dynamin 1; dynasore; endocytosis; epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Anticonvulsants / therapeutic use
  • Brain Waves
  • Dynamin I / genetics
  • Dynamin I / metabolism*
  • Epilepsy, Temporal Lobe / drug therapy
  • Epilepsy, Temporal Lobe / metabolism*
  • Epilepsy, Temporal Lobe / physiopathology
  • Female
  • Humans
  • Hydrazones / therapeutic use
  • Lithium / toxicity
  • Male
  • Pilocarpine / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time
  • Seizures / etiology
  • Seizures / metabolism*
  • Seizures / physiopathology
  • Up-Regulation*

Substances

  • Anticonvulsants
  • Hydrazones
  • N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
  • Pilocarpine
  • Lithium
  • Dynamin I