Abstract:
:Glucose-6-phosphate dehydrogenase (G6PD) protects the embryo from endogenous and xenobiotic-enhanced oxidative DNA damage and embryopathies. Here we show in aged mice that G6PD similarly protects against endogenous reactive oxygen species (ROS)-mediated neurodegeneration. In G6PD-normal (G6PD(+/+)) and heterozygous (G6PD(+/def)) and homozygous (G6PD(def/def)) G6PD-deficient male and female mice at about 2 years of age, oxidative DNA damage in various brain regions was assessed by 8-oxo-2'-deoxyguanosine formation using high-performance liquid chromatography and immunohistochemistry. Morphological changes in brain sections were assessed by H&E staining. DNA oxidation was increased in G6PD(def/def) mice in the cortex (p < 0.02), hippocampus (p < 0.01) and cerebellum (p < 0.006) compared to G6PD(+/+) mice, and was localized to distinct cell types. Histologically, in G6PD(+/def) mice, enhanced regionally and cellularly specific neurodegenerative changes were observed in those brain regions exhibiting elevated DNA oxidation, with a 53% reduction in the Purkinje cell count. These results show G6PD is important in protecting against the neurodegenerative effects of endogenous ROS in aging, and suggest that common hereditary G6PD deficiencies may constitute a risk factor for some neurodegenerative diseases.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Jeng W,Loniewska MM,Wells PGdoi
10.1021/cn400079ysubject
Has Abstractpub_date
2013-07-17 00:00:00pages
1123-32issue
7issn
1948-7193journal_volume
4pub_type
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