Reduced glutathione regenerating enzymes undergo developmental decline and sexual dimorphism in the rat cerebral...

Oxidative stress during development may predispose humans to neurodegenerative disorders in old age. Moreover, numerous ailments of brain disproportionately affect one of the genders. We therefore hypothesized that, activities of enzymes regenerating and utilizing glutathione (GSH) show sexual dimorphism and developmental differences in rat brain. To test this hypothesis, we collected cortex tissue from male and female Sprague-Dawley rats at post-natal day (PN) 5, PN 10, PN 20, PN 30, and PN 60. We measured tissue levels of NADP-linked isocitrate dehydrogenase (NADP-ICDH), glucose-6-phosphate dehydrogenase (G6PDH), and, glutathione reductase (GR) by UV spectrophotometry and determined glutathione peroxidase (GPx) expression therein by western blotting. Our results showed that sexual maturation had an impact on activities of enzymes that regenerate and utilize GSH and rat female cortex had more anti-oxidant capacity. Moreover, age-related decline in the activities of these key enzymes were observed. Reduced glutathione and NADPH protects the brain from oxidative stress. Thus, our results may have implications for neurodegenerative disorders like Parkinson's disease and developmental disorders of brain like autism in which oxidative stress plays a key role.