Qing Shang1,2, Jing Wang1,2, Zhijia Xi1,2, Baoyao Gao1,2, Hongyan Qian1,2, Ran An1,2, Gaojie Shao1,2, Hua Liu3, Tao Li4,5, Xinshe Liu6,7. 1. 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. 2. College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China. 3. Key Laboratory of Forensic Toxicology, Ministry of Public Security, Beijing, People's Republic of China. 4. 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. litao050428@xjtu.edu.cn. 5. College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China. litao050428@xjtu.edu.cn. 6. 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. lxins@mail.xjtu.edu.cn. 7. College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Yanta Road W.76, Xi'an, 710061, Shaanxi, People's Republic of China. lxins@mail.xjtu.edu.cn.
Abstract
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.
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.
Authors: Adrià Dangla-Valls; José Luis Molinuevo; Jordi Altirriba; Raquel Sánchez-Valle; Daniel Alcolea; Juan Fortea; Lorena Rami; Mircea Balasa; Cristina Muñoz-García; Mario Ezquerra; Rubén Fernández-Santiago; Alberto Lleó; Albert Lladó; Anna Antonell Journal: Mol Neurobiol Date: 2016-10-13 Impact factor: 5.590
Authors: V Brown; P Jin; S Ceman; J C Darnell; W T O'Donnell; S A Tenenbaum; X Jin; Y Feng; K D Wilkinson; J D Keene; R B Darnell; S T Warren Journal: Cell Date: 2001-11-16 Impact factor: 41.582
Authors: Yuri A Blednov; Jillian M Benavidez; Mendy Black; Laura B Ferguson; Grant L Schoenhard; Alison M Goate; Howard J Edenberg; Leah Wetherill; Victor Hesselbrock; Tatiana Foroud; R Adron Harris Journal: Alcohol Clin Exp Res Date: 2014-12-16 Impact factor: 3.928