Differential Gene Expression in the Hippocampi of Nonhuman Primates Chronically Exposed to Methamphetamine, Cocaine, or Heroin

被引:2
作者
Choi, Mi Ran [1 ]
Jin, Yeung-Bae [2 ]
Kim, Han-Na [3 ]
Lee, Heejin [4 ]
Chai, Young Gyu [5 ]
Lee, Sang-Rae [1 ,6 ]
Kim, Dai-Jin [4 ]
机构
[1] Ajou Univ, Lab Anim Res Ctr, Sch Med, Suwon, South Korea
[2] Gyeongsang Natl Univ, Dept Lab Anim Med, Coll Vet Med, Jinju, South Korea
[3] Korea Res Inst Biosci & Biotechnol, Natl Primate Res Ctr, Cheongju, South Korea
[4] Catholic Univ Korea, Seoul St Marys Hosp, Dept Psychiat, Coll Med, 222 Banpo Daero, Seoul 06591, South Korea
[5] Hanyang Univ, Dept Mol & Life Sci, Ansan, South Korea
[6] Ajou Univ, Dept Pharmacol, Sch Med, Suwon, South Korea
基金
新加坡国家研究基金会;
关键词
Cocaine; Heroin; Hippocampus; Methamphetamine; Gene expression profiling; LONG-TERM POTENTIATION; BOX RNA HELICASE; BETA-CATENIN; SYNAPTIC PLASTICITY; RAT-BRAIN; DDX3; ADAM10; MODEL; TRANSCRIPTION; ENHANCEMENT;
D O I
10.30773/pi.2022.0004
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
ObjectiveMethamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plastici-ty and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cyno-molgus monkeys in response to these drugs. MethodsAfter the monkeys were chronically exposed to MA, cocaine, and heroin, we performed large-scale gene expression profiling of the hippocampus using RNA-Seq technology and functional annotation of genes differentially expressed. Some genes selected from RNA-Seq analysis data were validated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). And the expression changes of ADAM10 protein were assessed using immunohistochemistry. ResultsThe changes in genes related to axonal guidance (PTPRP and KAL1), the cell cycle (TLK2), and the regulation of potassium ions (DPP10) in the drug-treated groups compared to the control group were confirmed using RT-qPCR. Comparative analysis of all groups showed that among genes related to synaptic long-term potentiation, CREBBP and GRIN3A were downregulated in both the MA- and heroin-treated groups compared to the control group. In particular, the mRNA and protein expression levels of ADAM10 were decreased in the MA-treated group but increased in the cocaine-treated group compared to the control group. ConclusionThese results provide insights into the genes that are upregulated and downregulated in the hippocampus by the chronic administration of MA, cocaine, or heroin and basic information for developing novel drugs for the treatment of hippocampal impair-ments caused by drug abuse
引用
收藏
页码:538 / +
页数:19
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