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

• 영문명: Differential Gene Expression in the Hippocampi of Nonhuman Primates Chronically Exposed to Methamphetamine, Cocaine, or Heroin
• 발행기관: 대한신경정신의학회
• 저자명: Mi Ran Choi Yeung-Bae Jin Han-Na Kim Heejin Lee Young Gyu Chai Sang-Rae Lee Dai-Jin Kim
• 간행물 정보: 『Psychiatry Investigation』제19권 제7호, 538~550쪽, 전체 13쪽
• 주제분류: 의약학 > 정신과학
• 파일형태: PDF
• 발행일자: 2022.07.31

영문 초록

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.

목차

INTRODUCTION

METHODS

RESULTS

DISCUSSION

키워드

Cocaine Heroin Hippocampus Methamphetamine Gene expression profiling