miRNA-222-3p 调控纳曲酮诱导的条件性位置偏爱形成的机制研究。
Mechanisms underlying microRNA-222-3p modulation of methamphetamine-induced conditioned place preference in the nucleus accumbens in mice.
机构信息
Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.
College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China.
出版信息
Psychopharmacology (Berl). 2022 Sep;239(9):2997-3008. doi: 10.1007/s00213-022-06183-9. Epub 2022 Jul 26.
RATIONALE
MicroRNA (miRNA) control of post-transcription gene expression in the nucleus accumbens (NAc) has been implicated in methamphetamine (METH) dependence. Conditioned place preference (CPP) is a classical animal procedure that reflects the rewarding effects of addictive drugs. miR-222-3p has been reported to play a key role in various neurological diseases and is strongly associated with alcohol dependence. Nevertheless, the role of miR-222-3p in METH dependence remains unclear.
OBJECTIVE
To explore the molecular mechanisms underlying the role of miR-222-3p in the NAc in METH-induced CPP.
METHODS
miR-222-3p expression in the NAc of METH-induced CPP mice was detected by quantitative real-time (qPCR). Following adeno-associated virus (AAV)-mediated overexpression or knockdown of miR-222-3p in the NAc, mice were subjected to CPP to investigate the effects of miR-222-3p on METH-induced CPP. Target genes of mir-222-3p were predicted using bioinformatics analysis. Candidate target genes for METH-induced CPP were validated by qPCR.
RESULTS
miR-222-3p expression in the NAc was decreased in CPP mice. Overexpression of miR-222-3p in the NAc blunted METH-induced CPP. Ppp3r1, Cdkn1c, Fmr1, and PPARGC1A were identified as target gene transcripts potentially mediating the effects of miR-222-3p on METH-induced CPP.
CONCLUSION
Our results highlight miR-222-3p as a key epigenetic regulator in METH-induced CPP and suggest a potential role for miR-222-3p in the regulation of METH-induced reward-related changes in the brain.
背景
微小 RNA（miRNA）在伏隔核（NAc）中的转录后基因表达调控与甲基苯丙胺（METH）依赖有关。条件性位置偏爱（CPP）是一种反映成瘾药物奖赏效应的经典动物程序。miR-222-3p 已被报道在各种神经疾病中发挥关键作用，并且与酒精依赖强烈相关。然而，miR-222-3p 在 METH 依赖中的作用尚不清楚。
目的
探讨 miR-222-3p 在 METH 诱导 CPP 中的 NAc 中的作用的分子机制。
方法
通过定量实时（qPCR）检测 METH 诱导 CPP 小鼠 NAc 中的 miR-222-3p 表达。通过腺相关病毒（AAV）介导的 miR-222-3p 在 NAc 中的过表达或敲低后，小鼠进行 CPP 以研究 miR-222-3p 对 METH 诱导 CPP 的影响。通过生物信息学分析预测 mir-222-3p 的靶基因。通过 qPCR 验证 METH 诱导 CPP 的候选靶基因。
结果
NAc 中的 miR-222-3p 表达在 CPP 小鼠中降低。在 NAc 中过表达 miR-222-3p 可减弱 METH 诱导的 CPP。Ppp3r1、Cdkn1c、Fmr1 和 PPARGC1A 被鉴定为潜在介导 miR-222-3p 对 METH 诱导 CPP 影响的靶基因转录本。
结论
我们的结果强调了 miR-222-3p 作为 METH 诱导 CPP 的关键表观遗传调节剂，并表明 miR-222-3p 在调节 METH 诱导的大脑奖赏相关变化中可能发挥作用。
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