DNA damage and synaptic and behavioural disorders in glucose-6-phosphate dehydrogenase-deficient mice.
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, γH2AX), 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. γH2AX 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.
['Loniewska|Margaret M|MM|', 'Gupta|Anmol|A|', 'Bhatia|Shama|S|', 'MacKay-Clackett|Isabel|I|', 'Jia|Zhengping|Z|', 'Wells|Peter G|PG|']
D000818:Animals D001921:Brain D053903:DNA Breaks, Double-Stranded D053904:DNA Breaks, Single-Stranded D004249:DNA Damage D004195:Disease Models, Animal D004789:Enzyme Activation D005260:Female D005954:Glucosephosphate Dehydrogenase D005955:Glucosephosphate Dehydrogenase Deficiency D008297:Male D001523:Mental Disorders D051379:Mice D010084:Oxidation-Reduction D011689:Purkinje Cells
DNA damage Behavioural disorders Glucose-6-phosphate dehydrogenase (G6PD) Reactive oxygen species (ROS) Aging Comet Electrophysiology Lifespan 8-Oxo-2′-deoxyguanine (8-oxodG) Gamma-H2AX (γH2AX) Neurodegeneration