Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea.
Basic Clin Pharmacol Toxicol. 2021 May;128(5):686-698. doi: 10.1111/bcpt.13554. Epub 2021 Jan 19.
Cocaine and heroin cause impairment of neural plasticity in the brain including striatum. This study aimed to identify genes differentially expressed in the striatum of cynomolgus monkeys in response to cocaine and heroin. After chronic administration of cocaine and heroin in the monkeys, we performed large-scale transcriptome profiling in the striatum using RNA-Seq technology and analysed functional annotation. We found that 547 and 1238 transcripts were more than 1.5-fold up- or down-regulated in cocaine- and heroin-treated groups, respectively, compared to the control group, and 3432 transcripts exhibited differential expression between cocaine- and heroin-treated groups. Functional annotation analysis indicated that genes associated with nervous system development (NAGLU, MOBP and TTL7) and stress granule disassembly (KIF5B and KLC1) were differentially expressed in the cocaine-treated group compared to the control group, whereas gene associated with neuron apoptotic process (ERBB3) was differentially expressed in the heroin-treated group. In addition, IPA network analysis indicated that genes (TRAF6 and TRAF3IP2) associated with inflammation were increased by the chronic administration of cocaine and heroin. These results provide insight into the correlated molecular mechanisms as well as the upregulation and down-regulation of genes in the striatum after chronic exposure to cocaine and heroin.
可卡因和海洛因会导致大脑纹状体等区域的神经可塑性受损。本研究旨在鉴定慢性给予可卡因和海洛因后食蟹猴纹状体中差异表达的基因。采用 RNA-Seq 技术进行大规模转录组谱分析，并进行功能注释。结果显示，与对照组相比，可卡因组和海洛因组分别有 547 个和 1238 个转录本的表达上调 1.5 倍以上，可卡因组和海洛因组之间有 3432 个转录本表达差异。功能注释分析表明，与神经系统发育相关的基因（NAGLU、MOBP 和 TTL7）和应激颗粒解体相关的基因（KIF5B 和 KLC1）在可卡因处理组中与对照组相比差异表达，而与神经元凋亡过程相关的基因（ERBB3）在海洛因处理组中差异表达。此外，IPA 网络分析表明，慢性给予可卡因和海洛因会增加与炎症相关的基因（TRAF6 和 TRAF3IP2）的表达。这些结果为深入了解慢性暴露于可卡因和海洛因后纹状体相关的分子机制以及基因的上调和下调提供了线索。
