Journal
REDOX BIOLOGY
Volume 28, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.redox.2019.101332
Keywords
Aging; Glucose-6-phosphate dehydrogenase (G6PD); Reactive oxygen species (ROS); DNA damage; 8-Oxo-2'-deoxyguanine (8-oxodG); Comet; Gamma-H2AX (gamma H2AX); Neurodegeneration; Behavioural disorders; Electrophysiology; Lifespan
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Funding
- Canadian Institutes of Health Research (CIHR)
- Faculty of Pharmacy, University of Toronto
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Mice deficient in glucose-6-phosphate dehydrogenase (G6PD) cannot replenish the cellular antioxidant glutathione, which detoxifies neurodegenerative reactive oxygen species (ROS). To determine the functional consequences of G6PD deficiency, young and aging G6PD-deficient mice were evaluated for brain G6PD activity, DNA damage (comets, gamma H2AX), Purkinje cell loss, brain function (electrophysiology, behaviour) and lifespan. DNA comet formation was increased and Purkinje cell counts were decreased in a G6pd gene dose-dependent fashion. gamma H2AX formation varied by age, sex and brain region, with increased levels in G6PD-deficient young and aging females, and in aging males. Aging male G6PD-deficient mice exhibited synaptic dysfunction in hippocampal slices. G6PD-deficient young and aging females exhibited deficits in executive function, and young deficient mice exhibited deficits in social dominance. Conversely, median lifespan in G6PD-deficient females and males was enhanced. Enhanced ROS-initiated brain damage in G6PD deficiency has functional consequences, suggesting that G6PD protects against ROS-mediated neurodegenerative disorders.
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