在雄性小鼠中,与阿片类药物诱导的奖励寻求和长期阿片类药物戒断相关的tRNA表观转录变化
Jennifer Blaze1,2,3, Caleb J Browne4,5,6, Rita Futamura4,5
1Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Jennifer.blaze@mssm.edu.
概括
慢性吗啡改变了大脑中的转移RNA (tRNA) 细胞因子甲基化,影响了基因表达和阿片类奖励行为. 这表明tRNA修饰是成的关键因素,也是潜在的治疗目标.
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.
- 成研究 研究成研究
背景情况:
- DNA甲基化与阿片类药物使用障碍有关.
- 在成中RNA细胞因子甲基化 (表转录组学) 仍未研究.
- 中间前额叶皮层 (mPFC) 对于奖励处理至关重要,并受到阿片类药物的影响.
研究的目的:
- 调查慢性吗啡暴露是否会改变mPFC中的tRNA细胞因子甲基化 (m5C) 和tRNA表达.
- 确定神经元Nsun2在阿片类药物奖励行为中的作用.
主要方法:
- 慢性吗啡在动物中的使用.
- 在mPFC中分析tRNA细胞因子甲基化和表达水平.
- 前脑全和区域mPFC对Nsun2基因的淘汰.
主要成果:
- 吗啡暴露动态改变了甘氨酸tRNA (tRNA^Gly_GCC) 的甲基化和表达.
- 戒药30天后,m5C增加和tRNA表达减少持续了30天.
- Nsun2淘汰赛扰乱了阿片类药物条件下的位置偏好.
结论:
- 慢性吗啡会改变tRNA regulome,在停止治疗后会产生持久的影响.
- 神经元Nsun2在调解阿片类药物奖励方面发挥着作用.
- tRNA细胞因子甲基化代表了一个新的成治疗标.
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