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Updated: May 26, 2026
Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Tocotrienols prevent hydrogen peroxide-induced axon and dendrite degeneration in cerebellar granule cells
Koji Fukui1, Keisuke Ushiki, Hirokatsu Takatsu
1Department of Bioscience and Engineering, College of Systems Engineering and Sciences, Shibaura Institute of Technology, Minuma-ku, Saitama, Japan.
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.
Insights
Tocotrienols protect neurons from hydrogen peroxide damage by preventing changes to collapsin response mediator protein-2 (CRMP-2) before cell death occurs. This neuroprotective effect highlights tocotrienols' potential in combating oxidative stress-related neuronal injury.
Area of Science:
- Neuroscience
- Oxidative Stress Biology
Background:
- Reactive oxygen species (ROS) are known to damage tissues and increase disease risk.
- ROS induce neuronal cell death in a concentration-dependent manner.
- Mechanisms of ROS-induced neuronal changes preceding cell death are not fully understood.
Purpose of the Study:
- To investigate the effects of hydrogen peroxide (H2O2) on cerebellar granule neurons (CGCs).
- To explore the protective role of tocotrienols against H2O2-induced neuronal damage.
- To elucidate the involvement of collapsin response mediator protein-2 (CRMP-2) in these processes.
Main Methods:
- Treatment of CGCs with hydrogen peroxide (0.5 μM).
- Assessment of axonal and dendritic morphology.
- Western blotting to detect changes in CRMP-2.
- Evaluation of tocotrienol isoform treatment effects.
Main Results:
- H2O2 induced axonal injury and significant dendrite degeneration (beading) in CGCs, without causing cell death.
- An abnormal band of CRMP-2 was detected in H2O2-treated CGCs.
- Tocotrienol treatment prevented axonal and dendrite degeneration and the induction of abnormal CRMP-2.
Conclusions:
- H2O2 causes pre-lethal neuronal damage, including axonal and dendritic alterations.
- Changes in CRMP-2 precede H2O2-induced neuronal death.
- Tocotrienols exhibit neuroprotective effects against H2O2 by preserving CRMP-2 integrity, suggesting therapeutic potential.
