快速的非基因雌激素信号控制酒精饮酒行为
Lia J Zallar1, Jean K Rivera-Irizarry2, Peter U Hamor3
1Pharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.
bioRxiv : the preprint server for biology
|November 14, 2023
概括
雌性小鼠的高雌激素水平通过快速大脑信号增加了饮酒过度,从而导致饮酒的性别差异. 这突显了雌激素在行为中的非基因机制.
科学领域:
- 神经内分泌学神经内分泌学
- 行为神经科学 行为神经科学
- 药理学 药理学是指药理学的学科.
背景情况:
- 雌激素通过基因组和非基因组途径影响生理过程,包括大脑中的快速神经元信号传递.
- 将雌激素与酒精消费行为联系在一起的机制,特别是性别差异,尚未完全理解.
- 早期饮酒对女性的酒精使用障碍的风险更高,过度饮酒与高雌激素水平相关.
研究的目的:
- 为了研究卵巢衍生的雌激素信号在驱动性饮酒中的因果作用,在性腺完整的雌性小鼠中.
- 阐明导致雌激素对与酒精有关的行为产生快速影响的特定大脑机制.
- 探索雌激素如何影响饮酒模式中的性别差异.
主要方法:
- 在雌性周期的不同阶段利用雌性小鼠来操纵循环中的雌激素水平.
- 评估酒精饮酒行为,包括暴饮暴食和避免饮酒.
- 研究了与膜相关的雌激素受体α (mERα) 在终端细胞 (BNST) 床核中的作用及其对皮质otropin释放因子 (CRF) 神经元的影响.
主要成果:
- 雌性小鼠在雌激素水平高 (孕期) 时,与低水平相比,显著增加了大量饮酒和减少了避开行为.
- 高内源性雌激素的饮酒效应是由通过mERα在BNST中的快速,非基因组信号传递的.
- 这种雌激素信号传递促进了CRF神经元的突触刺激,在饮酒期间增强了它们的活性.
结论:
- 这项研究首次证实了大脑中的快速,非基因性雌激素信号通路在完整的雌性哺乳动物中控制行为.
- 雌激素在自然的荷尔蒙环境中因果驱动酒精消费,导致酒精消费中已存在的性别差异.
- 这些发现意味着mERα信号在BNST中作为关键机制,将荷尔蒙波动与女性与酒精有关的行为联系起来.
相关概念视频
01:27CNS Depressants: Alcohol and Nicotine
220
Ethanol, a clear colorless alcohol, has been consumed by humans for millennia, but its effects on the body are far from benign. At lower doses, it induces decreased inhibitions and loquaciousness, leading to its social appeal. However, it can cause severe consequences at higher doses, such as coma and respiratory depression, due to its zero-order elimination kinetics. Chronic ethanol abuse wreaks havoc on multiple organ systems, particularly the CNS and the liver. Abrupt cessation of ethanol...
220
01:31Transducer Mechanism: Nuclear Receptors
1.4K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.4K
01:58Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K