Psychiatry Investig.
2022 Jul;19(7):538-550. 10.30773/pi.2022.0004.
Differential Gene Expression in the Hippocampi of Nonhuman Primates Chronically Exposed to Methamphetamine, Cocaine, or Heroin
- Affiliations
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- 1Laboratory Animal Research Center, Ajou University School of Medicine, Suwon, Republic of Korea
- 2Department of Laboratory Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea
- 3National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea
- 4Department of Psychiatry, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea
- 5Department of Molecular and Life Sciences, Hanyang University, Ansan, Republic of Korea
- 6Department of Pharmacology, Ajou University School of Medicine, Suwon, Republic of Korea
- KMID: 2532053
- DOI: http://doi.org/10.30773/pi.2022.0004
Abstract
Objective
Methamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plasticity and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cynomolgus monkeys in response to these drugs.
Methods
After 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.
Results
The 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.
Conclusion
These 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 impairments caused by drug abuse.
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