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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  ;  Ji Yeon Kim  ;  Jung Hwa Seo  ;  Eun Sook Park  ;  Chul Hoon Kim  ;  Hyongbum Kim  ;  Sung-Rae Cho 
Citation
 NEUROREHABILITATION AND NEURAL REPAIR, Vol.27(6) : 561-574, 2013 
Journal Title
 NEUROREHABILITATION AND NEURAL REPAIR 
ISSN
 1545-9683 
Issue Date
2013
MeSH
Analysis of Variance ; Animals ; Avoidance Learning/physiology ; Brain/metabolism* ; Dopamine Plasma Membrane Transport Proteins/genetics ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Dopamine and cAMP-Regulated Phosphoprotein 32/genetics ; Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism ; Enkephalins/genetics ; Enkephalins/metabolism ; Environment* ; Gene Expression Profiling ; Gene Expression Regulation/physiology* ; Interpersonal Relations ; Memory, Short-Term/physiology* ; Mice ; Mice, Inbred ICR ; Motor Activity/physiology* ; Neuronal Plasticity/physiology* ; Oligonucleotide Array Sequence Analysis ; Protein Precursors/genetics ; Protein Precursors/metabolism ; Receptors, Dopamine D1/genetics ; Receptors, Dopamine D1/metabolism ; Receptors, Purinergic P2Y12/genetics ; Receptors, Purinergic P2Y12/metabolism
Keywords
enriched environment ; gene expression ; gene set enrichment analysis ; synaptic activity
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.
Full Text
http://nnr.sagepub.com/content/27/6/561.long
DOI
10.1177/1545968313481277
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Park, Eun Sook(박은숙) ORCID logo https://orcid.org/0000-0002-9144-3063
Seo, Jung Hwa(서정화)
Yu, Ji Hea(유지혜)
Lee, Min Young(이민영)
Cho, Sung-Rae(조성래) ORCID logo https://orcid.org/0000-0003-1429-2684
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86769
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