Choi Mi Ran, Jin Yeung-Bae, Bang Sol Hee, Im Chang-Nim, Lee Youngjeon, Kim Han-Na, Chang Kyu-Tae, Lee Sang-Rae, Kim Dai-Jin
Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Korea.
Clin Psychopharmacol Neurosci. 2020 Feb 29;18(1):93-108. doi: 10.9758/cpn.2020.18.1.93.
The aim of this study was to investigate differentially expressed genes and their functions in the hippocampus and striatum after heroin administration in cynomolgus macaques of different ages.
Cynomolgus monkeys were divided by age as follows: 1 year (A1, n = 2); 3 to 4 years (A2, n = 2); 6 to 8 years (A3, n = 2); and older than 11 years (A4, n = 2). After heroin was injected intramuscularly into the monkeys (0.6 mg/kg), we performed large-scale transcriptome profiling in the hippocampus (H) and striatum (S) using RNA sequencing technology. Some genes were validated with real-time quantitative PCR.
In the hippocampus, the gene expression of A1H was similar to that of A4H, while the gene expression of A2H was similar to that of A3H. Genes associated with the mitogen-activated protein kinase signaling pathway (, and ) and γ-aminobutyric acid-ergic synapses ( and ) were differentially expressed among control and heroin-treated animals. Differential gene expression between A1S and A4S was the least significant, while differential gene expression between A3S and A2S was the most significant. Genes associated with the neurotrophin signaling pathway ( and ), autophagy (), and dopaminergic synapses () in the striatum were differentially expressed among control and heroin-treated animals.
These results suggest that even a single heroin exposure can cause differential gene expression in the hippocampus and striatum of nonhuman primates at different ages.
本研究旨在调查不同年龄食蟹猴注射海洛因后海马体和纹状体中差异表达的基因及其功能。
食蟹猴按年龄分组如下：1岁（A1组，n = 2）；3至4岁（A2组，n = 2）；6至8岁（A3组，n = 2）；11岁以上（A4组，n = 2）。给猴子肌肉注射海洛因（0.6 mg/kg）后，我们使用RNA测序技术对海马体（H）和纹状体（S）进行大规模转录组分析。一些基因通过实时定量PCR进行验证。
在海马体中，A1H的基因表达与A4H相似，而A2H的基因表达与A3H相似。在对照动物和海洛因处理的动物之间，与丝裂原活化蛋白激酶信号通路（、和）以及γ-氨基丁酸能突触（和）相关的基因存在差异表达。A1S和A4S之间的差异基因表达最不显著，而A3S和A2S之间的差异基因表达最显著。在对照动物和海洛因处理的动物之间，纹状体中与神经营养因子信号通路（和）、自噬（）以及多巴胺能突触（）相关的基因存在差异表达。
这些结果表明，即使单次接触海洛因也会导致不同年龄的非人灵长类动物海马体和纹状体中出现差异基因表达。
