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环状 RNA circTmeff-1 在小鼠吗啡成瘾记忆中的作用

The Role of circTmeff-1 in Morphine Addiction Memory of Mice.

机构信息

Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, College of Forensic Medicine, Hebei Medical University, Chinese Academy of Medical Sciences, Shijiazhuang 050000, China.

Department of Biogenetics, Qiqihar Medical University, Qiqihar 161000, China.

出版信息

Cells. 2023 Aug 1;12(15):1985. doi: 10.3390/cells12151985.

Abstract

In addition to the essential pharmacological effects of opioids, situational cues associated with drug addiction memory are key triggers for drug seeking. CircRNAs, an emerging hotspot regulator in crown genetics, play an important role in central nervous system-related diseases. However, the internal mediating mechanism of circRNAs in the field of drug reward and addiction memory remains unknown. Here, we trained mice on a conditional place preference (CPP) model and collected nucleus accumbens (NAc) tissues from day 1 (T0) and day 8 (T1) for high-throughput RNA sequencing. QRT-PCR analysis revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell, suggesting that it plays a role in addiction memory formation. Meanwhile, the down-regulation of circTmeff-1 by adeno-associated viruses in the NAc core or shell could inhibit the morphine CPP scores. Subsequently, the GO and KEGG analyses indicated that circTmeff-1 might regulate the addiction memory via the MAPK and AMPK pathways. These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory formation.

摘要

除了阿片类药物的基本药理作用外,与药物成瘾记忆相关的情境线索是药物寻求的关键触发因素。circRNAs 作为新兴的调控热点,在中枢神经系统相关疾病中发挥着重要作用。然而,circRNAs 在药物奖赏和成瘾记忆领域的内在介导机制尚不清楚。在这里,我们在条件性位置偏好 (CPP) 模型上对小鼠进行训练,并在第 1 天 (T0) 和第 8 天 (T1) 从伏隔核 (NAc) 组织中采集高通量 RNA 测序。QRT-PCR 分析显示,circTmeff-1 在 NAc 核心中高度表达,但在 NAc 壳中不表达,表明它在成瘾记忆形成中发挥作用。同时,腺相关病毒在 NAc 核心或壳中的下调可以抑制吗啡 CPP 评分。随后,GO 和 KEGG 分析表明,circTmeff-1 可能通过 MAPK 和 AMPK 途径调节成瘾记忆。这些发现表明,NAc 中的 circTmeff-1 在吗啡依赖记忆形成中起着关键作用。

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