TESTOSTERONE AND ETHANOL WITHDRAWAL NEUROTOXICITY

众所周知，酒精会导致选择性神经元退化。在 海马体，锥体神经元对酒精有选择性的易感性， 尤其是在戒毒期间。此外，在男性中，酒精含量很高 降低血液中的睾酮(T)水平。最近的证据表明 T可以起到神经保护作用。因此，与酒精相关的减少 循环中的T可能是锥体细胞在 戒酒。该项目的目标是评估 与酒精相关的睾丸素水平降低的原因 与酒精戒断相关的神经毒性。特定目标 1将讨论DHT(T的一种高度活跃的形式)的能力 对培养的海马锥体细胞的毒性作用 戒酒。具体目标2将解决同样的问题 活着。具体目标3将通过以下方式解决特定的分子机制 它可以减轻戒酒后的神经毒性。这个 从这项研究中获得的信息将对理解 酒精引起特定神经元的机制 退化。

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.