基因组胺的性别差异 状多巴胺的调节
Meghan Van Zandt1, Christopher Pittenger2,3,4,5,6
1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519.
概括
胺对雄性和雌性小鼠的大脑多巴胺的影响不同,通过不同的途径影响神经递质水平. 这种特定于性别的多巴胺调节可能解释了像图雷特综合征这样的神经精神疾病的差异.
科学领域:
- 神经科学是一个神经科学.
- 神经药理学神经药理学
- 内分泌学 在内分泌学.
背景情况:
- 基底质中的多巴胺系统失调与具有性别差异的神经精神疾病有关,例如图雷特综合征 (TS) 和多动症.
- 基因学研究在TS和动物模型中表明,胺素在多巴胺调节中的作用,可能涉及由于胺素损失导致的多巴胺失调.
研究的目的:
- 为了研究条性多巴胺由组胺的性别特异调节.
- 确定特定的组胺受体和大脑区域参与这些性别依赖的效应.
- 探索女性雌性周期对组胺胺对多巴胺调节的影响.
主要方法:
- 在小鼠中进行微透析以测量条纹性多巴胺水平.
- 使用基因素受体agonists和对抗剂的向药理学.
- 在特定的神经元群体中,shRNA对基因素受体的敲除.
- 监测女性雌性周期不同阶段的多巴胺水平.
主要成果:
- 脑内静脉内静脉 (ICV) 胰岛素给药降低了男性的条状多巴胺,通过黑色物质的H2受体 (SNc) 中介.
- 意想不到的是,ICV基因组胺在女性中增加了条形多巴胺,条形体中的H3受体发挥了关键作用.
- 组胺对雌性多巴胺的影响取决于雌性周期,仅在前雌性和雌性期间观察到,当雌激素水平高时.
结论:
- 组胺显著调节带状多巴胺,但这种调节表现出明显的性别差异.
- 在基因组胺-多巴胺通路中发现的性别差异,特别是涉及男性的H2R和女性的H3R,可能会导致神经精神疾病中的性别差异.
- 雌性周期依赖调制突出了女性激素和神经递质系统之间的复杂相互作用,为神经生物学性别差异提供了洞察力.
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