ly-379268 and Nerve-Degeneration

Glutamatergic 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.. Following 4-day binge alcohol exposure concurrent with LY379268 or vehicle treatment, Fluoro-Jade B and transforming growth factor-beta (TGF-beta) staining were carried out, and reversal learning in the Morris water maze was assessed.. Fluoro-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-beta expression in both the EC and dentate gyrus, whereas LY379268 increased TGF-beta in the EC only. Finally, neuroprotective effects of LY379268 were accompanied by prevention of deficits in spatial reversal learning.. Our data support a neuroprotective role for group II metabotropic glutamate receptor agonists and TGF-beta in alcohol-induced neurodegeneration.

Topics: Amino Acids; Analysis of Variance; Animals; Anxiety; Bridged Bicyclo Compounds, Heterocyclic; Cognition Disorders; Dose-Response Relationship, Drug; Drug Interactions; Ethanol; Fluoresceins; Gene Expression Regulation; Male; Maze Learning; Nerve Degeneration; Organic Chemicals; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate; Reversal Learning; Transforming Growth Factor beta

Topics: Amino Acids; Brain; Brain Ischemia; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cyclopropanes; Glycine; Hippocampus; Humans; Kainic Acid; Ligands; Nerve Degeneration; Neuroprotective Agents; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate