Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis
Article first published online: 17 OCT 2002
Journal of Neurochemistry
Volume 83, Issue 3, pages 535–545, November 2002
How to Cite
Jung, C., Higgins, C. M. J. and Xu, Z. (2002), Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis. Journal of Neurochemistry, 83: 535–545. doi: 10.1046/j.1471-4159.2002.01112.x
- Issue published online: 17 OCT 2002
- Article first published online: 17 OCT 2002
- Received April 29, 2002; revised manuscript received June 13, 2002; accepted June 15, 2002.
- amyotrophic lateral sclerosis;
- electron transport chain complex;
- motor neuron;
- reactive oxidative species
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease that causes degeneration of motoneurons. Mutation of Cu,Zn superoxide dismutase (SOD1) is one cause for this disease. In mice, expression of mutant protein causes motoneuron degeneration and paralysis resembling the human disease. Morphological change, indicative of mitochondrial damage, occurs at early stages of the disease. To determine whether mitochondrial function changes during the course of disease progression, enzyme activities of mitochondrial electron transport chain in spinal cords from mice at different disease stages were measured using three different methods: spectrophotometric assay, in situ histochemical enzyme assay, and blue native gel electrophoresis combined with in-gel histochemical reaction. The enzyme activities were decreased in the spinal cord, particularly in the ventral horn, beginning at early disease stages. This decrease persisted throughout the course of disease progression. This decrease was not detected in the spinal cords of non-transgenic animals, of mice expressing the wild-type protein, and in cerebellum and dorsal horn of the spinal cords from mice expressing mutant protein. These results demonstrate a functional defect in mitochondria in the ventral horn region and support the view that mitochondrial damage plays a role in mutant SOD1-induced motoneuron degeneration pathway.