PMID- 29476799 OWN - NLM STAT- MEDLINE DCOM- 20190415 LR - 20231213 IS - 1878-4216 (Electronic) IS - 0278-5846 (Linking) VI - 86 DP - 2018 Aug 30 TI - Effects of rhynchophylline on the hippocampal miRNA expression profile in ketamine-addicted rats. PG - 379-389 LID - S0278-5846(17)30894-1 [pii] LID - 10.1016/j.pnpbp.2018.02.009 [doi] AB - In the past few years, ketamine, a noncompetitive NMDA antagonist, has been widely abused worldwide as a new type of synthetic drug, severely affecting the physical and mental health of ketamine abusers. Previous studies have suggested that rhynchophylline can alleviate drug abuse and reverse the conditioned place preference caused by the abuse. MicroRNAs (miRNAs) are important factors regulating gene expression and are involved in the drug addiction process. The hippocampus is a critical area in the brain involved in causing drug addiction. However, the hippocampal miRNA expression profile and the effects of rhynchophylline on miRNA expression during ketamine abuse have not been reported. Thus, this study analyzed the hippocampal miRNA expression profile during ketamine-dependence formation and the effects of rhynchophylline on the differential expression of miRNAs induced by ketamine. The results of microarray analysis suggested that the expression levels of miR-331-5p were significantly different among three groups (the control, ketamine, and ketamine + rhynchophylline groups). miR-331-5p levels were significantly decreased in the ketamine model group and were upregulated in the ketamine + rhynchophylline group. Bioinformatics analysis of miR-331-5p and the 3' UTR of nuclear receptor related 1 protein (Nurr1) identified binding sites and showed downregulation, and the overexpression of miR-331-5p in hippocampal tissues showed that miR-331-5p is a negative transcription regulatory factor of Nurr1. Interestingly, we found that the downstream protein of Nurr1, brain-derived neurotrophic factor (BDNF), showed identical expression trends in the hippocampus as Nurr1. However, the transcription of the protein upstream of Nurr1, cyclic adenosine monophosphate response element-binding protein (CREB), did not show any significant differences between the ketamine group and the ketamine + rhynchophylline group. However, after rhynchophylline intervention, p-CREB showed significant differences between the ketamine and the ketamine + rhynchophylline groups. In summary, miR-331-5p is a key regulatory factor of Nurr1, and rhynchophylline can participate in the process of resistance to ketamine addiction through the miR-331-5p/Nurr1/BDNF pathway or inhibition of CREB phosphorylation. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Li, Chan AU - Li C AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. FAU - Tu, Genghong AU - Tu G AD - Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, China. FAU - Luo, Chaohua AU - Luo C AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. FAU - Guo, Youli AU - Guo Y AD - Department of Pharmacy, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, China. FAU - Fang, Miao AU - Fang M AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. FAU - Zhu, Chen AU - Zhu C AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. FAU - Li, Hancheng AU - Li H AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. FAU - Ou, Jinying AU - Ou J AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. FAU - Zhou, Yuting AU - Zhou Y AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. FAU - Liu, Wei AU - Liu W AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. FAU - Yung, Ken Kin Lam AU - Yung KKL AD - Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. FAU - Mo, Zhixian AU - Mo Z AD - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. Electronic address: cherrymo@fimmu.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180222 PL - England TA - Prog Neuropsychopharmacol Biol Psychiatry JT - Progress in neuro-psychopharmacology & biological psychiatry JID - 8211617 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, rat) RN - 0 (Central Nervous System Agents) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (MicroRNAs) RN - 0 (Nr4a2 protein, rat) RN - 0 (Nuclear Receptor Subfamily 4, Group A, Member 2) RN - 0 (Oxindoles) RN - 46BQ79VJ8D (rhyncophylline) RN - 690G0D6V8H (Ketamine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Central Nervous System Agents/*pharmacology MH - Computational Biology MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Disease Models, Animal MH - Gene Expression Regulation/drug effects MH - Hippocampus/*drug effects/metabolism MH - Ketamine/*administration & dosage MH - Male MH - MicroRNAs/*metabolism MH - Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism MH - Oxindoles/*pharmacology MH - Random Allocation MH - Rats, Sprague-Dawley MH - Substance-Related Disorders/*drug therapy/metabolism OTO - NOTNLM OT - BDNF OT - CREB OT - Ketamine addiction OT - Nurr1 OT - Rhynchophylline OT - miRNA EDAT- 2018/02/25 06:00 MHDA- 2019/04/16 06:00 CRDT- 2018/02/25 06:00 PHST- 2017/10/30 00:00 [received] PHST- 2018/02/01 00:00 [revised] PHST- 2018/02/21 00:00 [accepted] PHST- 2018/02/25 06:00 [pubmed] PHST- 2019/04/16 06:00 [medline] PHST- 2018/02/25 06:00 [entrez] AID - S0278-5846(17)30894-1 [pii] AID - 10.1016/j.pnpbp.2018.02.009 [doi] PST - ppublish SO - Prog Neuropsychopharmacol Biol Psychiatry. 2018 Aug 30;86:379-389. doi: 10.1016/j.pnpbp.2018.02.009. Epub 2018 Feb 22.