缺乏JMJD3会扰乱中脑中的多巴胺生物合成,并加剧慢性炎症性疼痛
Xi-Biao He1, Fang Guo2, Wei Zhang3
1Laboratory of Stem Cell Biology and Epigenetics, School of Basic Medical Sciences, Shanghai University of Medicine & Health Sciences, 279 Zhouzhu Highway, Pudong New Area, Shanghai, 201318, China. hexb@sumhs.edu.cn.
Acta neuropathologica communications
|December 24, 2024
概括
基因组脱甲基酶JMJD3调节中脑多巴胺 (mDA) 神经元中的多巴胺 (DA) 生物合成. 缺乏JMJD3会降低DA水平,并延长疼痛,影响大脑功能.
科学领域:
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 中脑多巴胺 (mDA) 神经元通过多巴胺 (DA) 生物合成调节关键的大脑功能.
- 控制mDA神经元中DA生物合成的表观遗传机制在很大程度上仍未被描述.
研究的目的:
- 研究JMJD3基因组脱甲酶在成人小鼠mDA神经元中调节DA生物合成中的作用.
- 阐明JMJD3在mDA神经元中的功能背后的分子机制.
主要方法:
- 成年小鼠中的Jmjd3有条件淘汰.
- 对JMJD的药理抑制3.
- 在中脑和条纹体中测量DA含量.
- 对TH和NURR1表达的组织学分析.
- 在体内和体外对基因转录和表观遗传修饰的机制研究.
- 对疼痛和运动功能的行为测试.
主要成果:
- 缺少Jmjd3导致中脑和条纹体中的DA含量减少.
- 在淘汰赛小鼠的mDA神经元中,TH和NURR1的表达下降.
- 由于增加了H3K27me3和减少了JMJD3/NURR1对基因促进者的结合,JMJD3缺乏抑制了Th和Nurr1转录.
- 条件淘汰的小鼠表现出长时间的炎症诱导的机械过敏症,而运动功能没有受到影响.
结论:
- 基因组脱甲基酶JMJD3是成年mDA神经元中DA生物合成的关键调节者.
- 由于DA水平下降,JMJD3缺乏会损害DA平衡,并导致慢性炎症性疼痛.
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