Hyperglycemia and high nitric oxide level induced oxidative stress in the brain and molecular alteration in the neurons and glial cells of laboratory mouse, Mus musculus

Chronic hyperglycemia (glucotoxicity) is reported to have detrimental effects on various brain functions leading to neurodegenerative changes. However, the effect of hyperglycemia in combination with high nitric oxide (NO) level (reported to be increased during glucotoxicity), on brain functions is not clear yet. The present study was designed to investigate the effects of hyperglycemic drug Streptozotocin (STZ) and NO donor Sodium nitroprusside (SNP) on the brain of laboratory mouse, Mus musculus. Effects of these conditions were studied on the markers of oxidative stress, NF-κB signalling and the markers of neuronal and glial cell activation/inflammation. Results indicate increased level of MDA and altered antioxidant enzymes activity in both the treated groups compared to control but high levels of AGEs, AOPP and AR activity (markers of diabetic complications) were observed in STZ group only. On the other hand, while STZ group showed decreased IL-6 level, it was increased in SNP group but IFN-ϒ level increased in both the treated groups compared to control. Further, in addition to alterations in the expressions of iNOS, IKKβ, IKBα and NF-κB subunits (RelA-p65/RelB-p50) observed in the neurons and glial cells of different brain regions (hypothalamus, basolateral amygdala and cerebral cortex), enhanced expression of microglial CD11b and astrocytic GFAP was also found in both the treated groups compared to control. Present findings led us to conclude that both hyperglycemia and high NO level causes oxidative stress in addition to molecular alteration in the neurons and glial cells. It is suggested that high blood glucose and NO level induced oxidative stress may lead to neuroinflammation possibly via NF-κB signalling. •Hyperglycemia and high NO level causes oxidative stress in the female mouse brain.•Both cause inflammatory responses by altering the levels of IL-6 and IFN-ϒ and induction of iNOS.•Hyperglycemia and high NO level causes activation of NF-κB signalling pathway.•Both augmented the activation of microglia and astroglia in stress prone different brain areas.