| Abstract No.: | B-G2199 |
| Country: | Canada |
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| Title: | MOTOR COORDINATION IN AGED AND METHYLENEDIOXYAMPHETAMINE (MDA)-TREATED WILD TYPE AND MUTANT GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD)-DEFICIENT MICE |
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| Authors/Affiliations: | 1 Margaret Loniewska*; 1,2 Peter Wells;
1 University of Toronto, Faculty of Pharmacy;
2 University of Toronto, Department of Pharmacology and Toxicology, Toronto, ON, Canada. |
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| Content: | Objective: Glucose-6-phosphate dehydrogenase (G6PD) is important for regenerating the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for the detoxification of reactive oxygen species (ROS), including free radicals and hydroperoxides. NADPH also maintains the catalytic activity of catalase, which detoxifies hydrogen peroxide. It is generally believed that G6PD deficiencies constitute a problem only for mature red blood cells; however, we have shown the embryoprotective role of G6PD against developmental oxidative stress and chemical teratogenesis. Using G6PD-deficient mice, we sought to determine if G6PD plays a similar protective role in neurodegeneration associated with aging and exposure to amphetamines, both of which may involve ROS, although the molecular mechanisms remain unclear.
Methods: Motor coordination was measured in young and aged G6PD-normal and mutant G6PD-deficient mice using a rotarod apparatus. Also, a small number of G6PD-normal and G6PD-deficient mice were similarly evaluated before and after treatment with the primary methylenedioxymethamphetamine (MDMA, Ecstasy) metabolite methylenedioxyamphetamine (MDA).
Results: Motor coordination was significantly reduced in aged G6PD-normal female mice but not in the males, nor in heterozygous or homozygous G6PD-deficient female mice. Young female G6PD-normal mice showed significantly better motor coordination compared to homozygous G6PD-deficient females and both male genoptypes. MDA-treated mice exhibited enhanced learning compared to vehicle controls, but no differences were apparent among the genotypes. The MDA results are preliminary due to a small sample size.
Conclusions: The risk of enhanced ROS-mediated neurodegeneration in aged G6PD-deficient mice may have important clinical implications for aging people, since G6PD deficiencies constitute the most common human enzymopathy, affecting over 400 million people and up to 60% of some populations. (Support: CIHR)
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