Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.123
Gene Expression Profiling in the Striatum of Per2 KO Mice Exhibiting More Vulnerable Responses against Methamphetamine
Mikyung Kim1,2,†, Se Jin Jeon3,†, Raly James Custodio1, Hyun Jun Lee1, Leandro Val Sayson1, Darlene Mae D. Ortiz1, Jae Hoon Cheong1,* and Hee Jin Kim1,*
1Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, Seoul 01795,
2Department of Chemistry Life Science, Sahmyook University, Seoul 01795,
3School of Medicine and Center for Neuroscience Research, Konkuk University, Seoul 05029, Republic of Korea
*E-mail: hjkim@syu.ac.kr (Kim HJ), cheongjh@syu.ac.kr (Cheong JH)
Tel: +82-2-3399-1609 (Kim HJ), +82-2-3399-1605 (Cheong JH)
Fax: +82-2-3399-1619 (Kim HJ), +82-2-3399-1619 (Cheong JH)
†The first two authors contributed equally to this work.
Received: July 9, 2020; Revised: August 20, 2020; Accepted: August 23, 2020; Published online: December 21, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Drug addiction influences most communities directly or indirectly. Increasing studies have reported the relationship between circadian-related genes and drug addiction. Per2 disrupted mice exhibited more vulnerable behavioral responses against some drugs including methamphetamine (METH). However, its roles and mechanisms are still not clear. Transcriptional profiling analysis in Per2 knockout (KO) mice may provide a valuable tool to identify potential genetic involvement and pathways in enhanced behavioral responses against drugs. To explore the potential genetic involvement, we examined common differentially expressed genes (DEGs) in the striatum of drug naïve Per2 KO/wild-type (WT) mice, and before/after METH treatment in Per2 KO mice, but not in WT mice. We selected 9 common DEGs (Ncald, Cpa6, Pklr, Ttc29, Cbr2, Egr2, Prg4, Lcn2, and Camsap2) based on literature research. Among the common DEGs, Ncald, Cpa6, Pklr, and Ttc29 showed higher expression levels in drug naïve Per2 KO mice than in WT mice, while they were downregulated in Per2 KO mice after METH treatment. In contrast, Cbr2, Egr2, Prg4, Lcn2, and Camsap2 exhibited lower expression levels in drug naïve Per2 KO mice than in WT mice, while they were upregulated after METH treatment in Per2 KO mice. qRT-PCR analyses validated the expression patterns of 9 target genes before/after METH treatment in Per2 KO and WT mice. Although further research is required to deeply understand the relationship and roles of the 9 target genes in drug addiction, the findings from the present study indicate that the target genes might play important roles in drug addiction.
Keywords: Addiction, Methamphetamine, Per2, Gene expression

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