Tocotrienols prevent hydrogen peroxide-induced axon and dendrite degeneration in cerebellar granule cells

Free Radic Res. 2012 Feb;46(2):184-93. doi: 10.3109/10715762.2011.647689. Epub 2012 Jan 23.

Abstract

It is well known that reactive oxygen species (ROS) attack several living tissues and increase the risk of development and progression of serious diseases. In neuronal level, ROS induce cell death in concentration-dependent fashion. However, little is known about the mechanisms of neuronal changes by ROS prior to induction of cell death. Here we found that treatment of cerebellar granule neurons (CGCs) with 0.5 μM hydrogen peroxide induced axonal injury, but not cell death. The number of dendrites remarkably decreased in hydrogen peroxide-treated CGCs, and extensive beading was observed on survival dendrites. In addition, an abnormal band of the original collapsin response mediator protein (CRMP)-2 was detected by Western blotting in hydrogen peroxide-treated CGCs. Treatment with each tocotrienol isoform prevented axonal and dendrite degeneration and induction of the abnormal band of the original band of CRMP-2 in hydrogen peroxide-treated CGCs. These results indicate that treatment with tocotrienols may therefore be neuroprotective in the presence of hydrogen peroxide by preventing changes to the CRMP-2 that occur before neuron death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Axons / drug effects
  • Axons / metabolism
  • Axons / pathology*
  • Axons / physiology
  • Cells, Cultured
  • Cerebellum / pathology*
  • Chromans / pharmacology*
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Dendrites / pathology*
  • Dendrites / physiology
  • Free Radical Scavengers / pharmacology
  • Hydrogen Peroxide
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lipid Peroxidation
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Nerve Degeneration
  • Nerve Tissue Proteins / metabolism
  • Neuroprotective Agents / pharmacology*
  • Primary Cell Culture
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Tocotrienols
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology

Substances

  • Chromans
  • Free Radical Scavengers
  • Intercellular Signaling Peptides and Proteins
  • MAP1LC3 protein, mouse
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Thiobarbituric Acid Reactive Substances
  • Tocotrienols
  • collapsin response mediator protein-2
  • Vitamin E
  • plastochromanol 8
  • tocotrienol, alpha
  • Hydrogen Peroxide