Defects in Glutathione System in an Animal Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progredient neurodegenerative disease characterized by a degeneration of the first and second motor neurons. Elevated levels of reactive oxygen species (ROS) and decreased levels of glutathione, which are important defense mechanisms against ROS, have been reported in the central nervous system (CNS) of ALS patients and animal models. The aim of this study was to determine the cause of decreased glutathione levels in the CNS of the ALS model wobbler mouse. We analyzed changes in glutathione metabolism in the spinal cord, hippocampus, cerebellum, liver, and blood samples of the ALS model, wobbler mouse, using qPCR, Western Blot, HPLC, and fluorometric assays. Here, we show for the first time a decreased expression of enzymes involved in glutathione synthesis in the cervical spinal cord of wobbler mice. We provide evidence for a deficient glutathione metabolism, which is not restricted to the nervous system, but can be seen in various tissues of the wobbler mouse. This deficient system is most likely the reason for an inefficient antioxidative system and, thus, for elevated ROS levels.