Chunk #24 — Mechanisms of Neurodegeneration Related to Alcohol’s Effects on Neuroimmune Signaling in the Brain — Role of NADPH Oxidase and Oxidative Stress
Qin and Crews (2012b) discovered that LPS and ethanol can increase expression of NADPH oxidase subunits, particularly the superoxide-forming gp91phox subunit, in the brain and that ethanol treatment of mice increased superoxide formation in the brain as well as neuronal death. Inhibition of oxidases both reduced superoxide formation and protected against alcohol-induced neuronal death. Other studies in mice demonstrated that LPS treatment induced neuroimmune-gene expression, NADPH-oxidase activity, and oxidative stress that persisted for at least 20 months and led to neurodegeneration (Qin et al. 2013). Prolonged induction of NADPH oxidase and oxidative stress in the brain could contribute to the persistent increase in NF-κB transcription observed after alcohol exposure, because ROS can activate NF-κB. These findings are consistent with the hypothesis that oxidative stress, by inducing innate immune genes, significantly contributes to alcoholic brain damage and alcoholic neurodegeneration.
