Co-treatment with riluzole, a neuroprotective drug, ameliorates the 3-acetylpyridine-induced neurotoxicity in cerebellar Purkinje neurones of rats: behavioural and electrophysiological evidence

Neurotoxicology. 2009 May;30(3):393-402. doi: 10.1016/j.neuro.2009.02.014. Epub 2009 Mar 5.

Abstract

Riluzole has been shown to possess neuroprotective effects in a variety of neurological and animal model of diseases, including motor diseases. However, the mechanism(s) by which riluzole preserves the intrinsic electrophysiological characteristics of neuronal membrane has not been fully delineated. Ataxia is a clinical manifestation of disturbance in coordinated motor activity, which may be caused by cerebellar impairment. Here, the in vivo neuroprotective effect of riluzole on the intrinsic activity of Purkinje cells (PCs) in a rat model of cerebellar ataxia induced by 3-acetylpyridine (3-AP) was studied. Behavioural assessment tests, histological examination and whole cell patch clamp recording under current clamp conditions were used to explore the possible protective effect of riluzole against induction of ataxia with 3-AP treatment. Combined treatment with riluzole and 3-AP not only almost completely prevented the neuronal degeneration in cerebellar Purkinje cells layer but also the development of ataxia, which occurred following injection of 3-AP alone and partially improved the motor behaviour in comparison with ataxic rats. The normal firing behaviour and action potential characteristics of Purkinje neurones were preserved. The amplitude of both fast after hyperpolarization potential (fAHP) and post train after hyperpolarization potential, a marker of slow AHP (sAHP), along with the duration of post train AHP, which play an important role in regulating the firing behaviour were restored to the control conditions. These findings suggest that riluzole-induced neuroprotection may be mediated at least in part by activation of Ca(2+)-dependent K(+) channel function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Cerebellar Ataxia / chemically induced
  • Cerebellar Ataxia / pathology
  • Cerebellar Ataxia / physiopathology*
  • Cerebellum / anatomy & histology
  • Cerebellum / physiology
  • Drug Interactions
  • Male
  • Motor Activity / drug effects*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins / antagonists & inhibitors*
  • Neurotoxins / toxicity*
  • Purkinje Cells* / cytology
  • Purkinje Cells* / drug effects
  • Purkinje Cells* / physiology
  • Pyridines / antagonists & inhibitors*
  • Pyridines / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Riluzole / administration & dosage*
  • Riluzole / pharmacology*

Substances

  • Neuroprotective Agents
  • Neurotoxins
  • Pyridines
  • 3-acetylpyridine
  • Riluzole