人类神经精神疾病风险基因Drd2对于跨进化远端物种的社会功能是必要的
Kevin G O Ike1, Sanne J C Lamers1, Soumya Kaim1
1Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands.
Molecular psychiatry
|December 19, 2023
概括
多巴胺D2受体 (D2R) 基因调节跨物种的社会行为. 它的激活对社会功能至关重要,这表明神经精神疾病的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 伦理学 伦理学 伦理学
背景情况:
- 由Drd2基因编码的多巴胺D2受体 (D2R) 与神经精神疾病中出现的社会退缩有关.
- 在像Drosophila melanogaster和小鼠这样的模型生物中观察到社会退缩,这些生物共享与人类疾病相关的基因.
研究的目的:
- 为了确定Drd2和社交性之间的因果关系.
- 调查Drd2在社会行为中的进化保守功能.
- 评估D2R作为社会功能障碍的潜在治疗点.
主要方法:
- 在D. melanogaster.中对Drd2同类突变的行为观察.
- 在半自然环境中对条件转基因小鼠 (自受体KO和异受体KO) 的分析.
- 在野生类型小鼠中使用D2R激动剂和对抗剂的药理干预.
- 计算的伦理学方法.
主要成果:
- 中的Drd2突变体表现出社会相互作用和运动活动的减少.
- 在多巴胺基细胞 (自受体KOs) 中缺乏Drd2的小鼠表现出增加的社交性,但活动减少.
- 在野生型小鼠中,D2R激动剂的使用降低了社交能力;对抗剂没有影响.
- 在血清激素细胞中的Drd2删除并没有显著影响社交能力.
结论:
- Drd2 在调节进化上相距较远的物种之间的社交性方面发挥着保留的作用.
- 哺乳动物D2R自身受体的激活对于正常的社会功能至关重要.
- 在神经精神疾病中,Drd2和D2R信号代表了社会缺陷的潜在治疗途径.
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