Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD, United States.
Front Neural Circuits. 2022 Jun 22;16:702901. doi: 10.3389/fncir.2022.702901. eCollection 2022.
Exposure to alcohol has multiple effects on nervous system function, and organisms have evolved mechanisms to optimally respond to the presence of ethanol. Sex differences in ethanol-induced behaviors have been observed in several organisms, ranging from humans to invertebrates. However, the molecular mechanisms underlying the dimorphic regulation of ethanol-induced behaviors remain incompletely understood. Here, we observed sex differences in ethanol sedation sensitivity in Genome Reference Panel (DGRP) lines of compared to the absence of dimorphism in standard laboratory wildtype and control lines. However, in dose response experiments, we were able to unmask dimorphic responses for the control mutant line by lowering the testing ethanol concentration. Notably, feminization of the small population of Corazonin (Crz) neurons in males was sufficient to induce female-like sedation sensitivity. We also tested the role of the transcription factor () based on its known expression in Crz neurons and its regulation of sedation responses. Interestingly, loss of function mutations increased sedation times in both males and females as compared to controls. No significant difference between male and female mutants was observed, suggesting a possible role of in the regulation of dimorphic ethanol-induced responses. Thus, our results shed light into the mechanisms regulating sex-differences in ethanol-induced behaviors at the cellular and molecular level, suggesting that the genetic sex in a small neuronal population plays an important role in modulating sex differences in behavioral responses to ethanol.
暴露于酒精会对神经系统功能产生多种影响，而生物体已经进化出了最佳的机制来应对乙醇的存在。在从人类到无脊椎动物的几种生物体中，都观察到了乙醇诱导的行为存在性别差异。然而，乙醇诱导行为的二态性调节的分子机制仍不完全清楚。在这里，我们观察到与标准实验室野生型和对照品系中不存在二态性相比， 基因组参考品系（DGRP）品系中乙醇镇静敏感性存在性别差异。然而，在剂量反应实验中，我们能够通过降低测试乙醇浓度来揭示对照突变体系 的二态性反应。值得注意的是，雄性中 Corazonin（Crz）神经元的小型群体的雌性化足以诱导类似雌性的镇静敏感性。我们还测试了转录因子 （）的作用，基于其在 Crz 神经元中的已知表达及其对镇静反应的调节。有趣的是，与对照相比，功能丧失 突变增加了雄性和雌性的镇静时间。在 突变体中未观察到雄性和雌性之间的显著差异，这表明 可能在调节二态性乙醇诱导反应中起作用。因此，我们的结果揭示了在细胞和分子水平上调节乙醇诱导行为性别差异的机制，表明在一个小神经元群体中的遗传性别在调节对乙醇的行为反应的性别差异方面起着重要作用。
