GFOD1 regulates oxidative stress-induced damage in ADHD via NF-κB signaling pathway

Attention-deficit/hyperactivity disorder (ADHD) is a mental behavioral disorder that poses a serious health risk. Oxidative stress, which damages the function of neurons and astrocytes, has been discovered as a key factor contributing to ADHD pathology. A newly identified gene, Glucose-fructose oxidoreductase domain 1 (GFOD1), may be linked to the development of ADHD. It plays a role in regulating oxidative stress in ADHD; however, its exact role is unclear. This manuscript investigates the changes of GFOD1 expression and aim to correlate this with oxidative stress induced by NF-kappa B signaling pathway in the rat brains with ADHD and in vitro astrocytes. Our results revealed an increase in GFOD1 expression in the prefrontal cortex and cerebellar cortex of rats with ADHD, accompanied by neuronal injury and increased glial fibrillary acidic protein (GFAP) expression in astrocytes, concomitant with activation of the NF-kappa B p65/NOX2 signaling pathway. Along with this, GFOD1 overexpression in astrocytes resulted in an up-regulation of this signaling pathway similarly. Both ADHD rats and astrocytes in overexpressing GFOD1 showed elevated levels of reactive oxygen species (ROS) and Malondialdehyde (MDA), reduced activity of superoxide dismutase (SOD). Furthermore, treatment with the methylphenidate (MPH) did not affect GFOD1 expression. But it impacted the levels of oxidative stress mediated by the NF kappa B p65/NOX2 signaling pathway. Overall, it is suggested that GFOD1 may contribute to increased levels of oxidative stress specifically in the prefrontal cortex and cerebellar cortex regions and astrocytes affected by ADHD via up-regulation of the NF-kappa B p65/NOX2/oxidative stress axis.