TESTOSTERONE AND ETHANOL WITHDRAWAL NEUROTOXICITY

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Alcohol is known to cause selective neuronal degeneration. In the hippocampus, pyramidal neurons are selectively vulnerable to alcohol, especially during withdrawal. In addition, in males, alcohol acutely decreases circulating testosterone(T) levels. Recent evidence suggests that T can be neuroprotective. Therefore, alcohol-related reduction in circulating T may contribute to the pyramidal cell's vulnerability during alcohol withdrawal. The goal of this project is to assess the contribution of lowered testosterone levels, which accompany alcohol consumption, to alcohol withdrawal-related neurotoxicity. Specific aim 1 will address the ability of DHT (a highly active form of T) to attenuate toxicity to cultured hippocampal pyramidal cells following alcohol withdrawal. Specific aim 2 will address the same question in vivo. Specific aim 3 will address the specific molecular mechanism by which DHT is attenuating neurotoxicity following alcohol withdrawal. The information gained from this research will be-valuable in understanding the mechanisms by which alcohol is causing specific neuronal degeneration.