Inflammatory stress in the cerebellum: implications for nutritional intervention in alcohol-mediated CNS damage

Abstract

Presently there are no effective disease-modifying treatments to combat neurodegeneration among chronic alcoholics. Alcohol abuse imparts a sustained presence of oxidative stressors, including pro-inflammatory cytokine TNFα, in the brain. A persistent presence of TNFα leads to an accumulation of reactive oxygen species, which promotes oxidative damage, subsequent neurodegeneration, and ultimately permanent cognitive changes in afflicted individuals. Our laboratory has demonstrated the potency of ursolic acid, isolated from Alaskan blueberries, to abolish TNFα mediated neurotoxicity in human neuroblastoma cells. Our current study investigated the neuroinflammatory effects of ethanol and TNFα on dissociated neurons and glia cells cultured from embryonic chicks while quantitatively evaluating the preventive and therapeutic effectiveness of blueberry extracts. We compared both CNS and PNS neurons to examine correlations to clinically indicated neurodegeneration. Our results clearly revealed a particular sensitivity of cerebellar neurons to oxidative stress; however, supplementation with blueberry extracts rescued neuronal health by up-regulating antioxidant defenses, suppressing TNFα secretion, blunting lipid peroxidation, restoring cytoskeleton organization, modulating lipid rafts and altering the lipid environment of ion channels. Implementation of blueberries into the diet may offer an inexpensive and safe means to improve quality of life and reduce future health care costs associated with alcohol abuse and neurodegenerative disease.