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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

Authors
 Min-Young Lee ; Ji Hea Yu ; Sung-Rae Cho ; Hyongbum Kim ; Chul Hoon Kim ; Eun Sook Park ; Jung Hwa Seo ; Ji Yeon Kim 
Citation
 Neurorehabilitation and Neural Repair, Vol.27(6) : 561~574, 2013 
Journal Title
 Neurorehabilitation and Neural Repair 
ISSN
 1545-9683 
Issue Date
2013
Abstract
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/86769
DOI
10.1177/1545968313481277
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
1. 연구논문 > 1. College of Medicine > Dept. of Rehabilitation Medicine
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
Yonsei Authors
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Link
 http://nnr.sagepub.com/content/27/6/561.long
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