Alcohol-Induced Neurodegeneration, Suppression of Transforming Growth Factor-β, and Cognitive Impairment in Rats: Prevention by Group II Metabotropic Glutamate Receptor Activation

BackgroundGlutamatergic neurotransmission has been implicated in mechanisms of alcohol-induced neurodegeneration and cognitive impairment, but the underlying mechanism remains unknown. Here, we examined whether the group II metabotropic glutamate receptor agonist LY379268 prevents neuronal death and learning deficits in a rat model of binge-like exposure to alcohol.MethodsFollowing 4-day binge alcohol exposure concurrent with LY379268 or vehicle treatment, Fluoro-Jade B and transforming growth factor-β (TGF-β) staining were carried out, and reversal learning in the Morris water maze was assessed.ResultsFluoro-Jade B staining indicating neurodegeneration was most extensive in the ventral hippocampus and the entorhinal cortex (EC). LY379268 was potently neuroprotective in the EC but not in the dentate gyrus of the hippocampus. In parallel, binge alcohol exposure suppressed TGF-β expression in both the EC and dentate gyrus, whereas LY379268 increased TGF-β in the EC only. Finally, neuroprotective effects of LY379268 were accompanied by prevention of deficits in spatial reversal learning.ConclusionsOur data support a neuroprotective role for group II metabotropic glutamate receptor agonists and TGF-β in alcohol-induced neurodegeneration.