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Alteration of Synaptic Activity–Regulating Genes Underlying Functional Improvement by Long-term Exposure to an Enriched Environment in the Adult Brain

 Min-Young Lee  ;  Ji Hea Yu  ;  Ji Yeon Kim  ;  Jung Hwa Seo  ;  Eun Sook Park  ;  Chul Hoon Kim  ;  Hyongbum Kim  ;  Sung-Rae Cho 
 Neurorehabilitation and Neural Repair, Vol.27(6) : 561-574, 2013 
Journal Title
 Neurorehabilitation and Neural Repair 
Issue Date
Background. Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. Objectives. We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. Methods. We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). Results. In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na+/Cl−-dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. Conclusion. An EE enhanced motor and cognitive function through the alteration of synaptic activity–regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
Yonsei Authors
김철훈(Kim, Chul Hoon) ORCID logo https://orcid.org/0000-0002-7360-429X
박은숙(Park, Eun Sook) ORCID logo https://orcid.org/0000-0002-9144-3063
서정화(Seo, Jung Hwa)
유지혜(Yu, Ji Hea)
이민영(Lee, Min Young)
조성래(Cho, Sung-Rae) ORCID logo https://orcid.org/0000-0003-1429-2684
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