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  • SAGE Publications  (4)
  • Yu, Ji Hea  (4)
  • 1
    Online Resource
    Online Resource
    Early Immunomodulation by Intravenously Transplanted Mesenchymal Stem Cells Promotes Functional Recovery in Spinal Cord Injured Rats
    SAGE Publications ; 2011
    In:  Cell Medicine Vol. 2, No. 2 ( 2011-07), p. 55-68
    Details
    In: Cell Medicine, SAGE Publications, Vol. 2, No. 2 ( 2011-07), p. 55-68
    Abstract: Although intravenous administration of mesenchymal stem cells (MSCs) can enhance functional recovery after spinal cord injury (SCI), the underlying mechanisms have to be elucidated. In this study, we explored the mechanisms for functional recovery in SCI rats after intravenous transplantation of MSCs derived from human umbilical cord blood. Sprague-Dawley rats were randomly assigned to receive either MSCs (1 × 10 6 cells/0.5 ml) or PBS into the tail vein immediately after SCI. They were then evaluated by the Basso-Beattie-Bresnahan (BBB) locomotor rating scale weekly for 8 weeks and by somatosensory evoked potentials (SSEPs) 8 weeks after transplantation. MSC-treated rats showed a modest but significant improvement in BBB scores and latencies of SSEPs, compared with PBS controls. When human-specific Alu element was measured in the spinal cord, it was detected only 1 h after transplantation, suggesting transient engraftment of MSCs. Inflammatory cytokines were also determined using RT-PCR or Western blot in spinal cord extracts. In MSC-treated rats, the level of proinflammatory cytokine IL-1β was decreased, but that of antiinflammatory cytokine IL-10 was increased. MSCs also immediately suppressed IL-6 at 1 h posttransplantation. However, the response of IL-6, which has an immunoregulatory role, was increased 1–3 days after transplantation. In addition, we quantified microglia/macrophage stained with Iba-1 around the damaged spinal cord using immunohistochemistry. A proportion of activated microglia and macrophages in total Iba-1 + cells was significantly decreased in MSC-treated rats, compared with PBS controls. These results suggest that early immunomodulation by intravenously transplanted MSCs is a potential underlying mechanism for functional recovery after SCI.
    Type of Medium: Online Resource
    ISSN: 2155-1790 , 2155-1790
    URL: Article
    DOI: 10.3727/215517911X582788
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2011
    detail.hit.zdb_id: 2634804-4
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  • 2
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    Environmental Enrichment Synergistically Improves Functional Recovery by Transplanted Adipose Stem Cells in Chronic Hypoxic-Ischemic Brain Injury
    SAGE Publications ; 2013
    In:  Cell Transplantation Vol. 22, No. 9 ( 2013-09), p. 1553-1568
    Details
    In: Cell Transplantation, SAGE Publications, Vol. 22, No. 9 ( 2013-09), p. 1553-1568
    Abstract: We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O 2 for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE ( n = 18), ASC-SC ( n = 19), PBS-EE ( n = 12), PBS-SC ( n = 17), and untreated controls ( n = 23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation, and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin + neurons derived from the transplanted ASCs was significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increased BrdU + βIII-tubulin + neurons, GFAP + astrocytic density, and fibroblast growth factor 2 (FGF2) level but not the level of CS-56 + glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    URL: Article
    DOI: 10.3727/096368912X662390
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
    detail.hit.zdb_id: 2020466-8
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  • 3
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    Environmental enrichment enhances synaptic plasticity by internalization of striatal dopamine transporters
    SAGE Publications ; 2016
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 36, No. 12 ( 2016-12), p. 2122-2133
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 36, No. 12 ( 2016-12), p. 2122-2133
    Abstract: Environmental enrichment (EE) with a complex combination of physical, cognitive and social stimulations enhances synaptic plasticity and behavioral function. However, the mechanism remains to be elucidated in detail. We aimed to investigate dopamine-related synaptic plasticity underlying functional improvement after EE. For this, six-week-old CD-1 mice were randomly allocated to EE or standard conditions for two months. EE significantly enhanced behavioral functions such as rotarod and ladder walking tests. In a [ 18 F]FPCIT positron emission tomography scan, binding values of striatal DAT were significantly decreased approximately 18% in the EE mice relative to the control mice. DAT inhibitor administrated to establish the relationship of the DAT down-regulation to the treatment effects also improved rotarod performances, suggesting that DAT inhibition recapitulated EE-mediated treatment benefits. Next, EE-induced internalization of DAT was confirmed using a surface biotinylation assay. In situ proximity ligation assay and immunoprecipitation demonstrated that EE significantly increased the phosphorylation of striatal DAT as well as the levels of DAT bound with protein kinase C (PKC). In conclusion, we suggest that EE enables phosphorylation of striatal DAT via a PKC-mediated pathway and causes DAT internalization. This is the first report to suggest an EE-mediated mechanism of synaptic plasticity by internalization of striatal DAT.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X15613525
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2039456-1
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  • 4
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    Online Resource
    Alteration of Synaptic Activity–Regulating Genes Underlying Functional Improvement by Long-term Exposure to an Enriched Environment in the Adult Brain
    SAGE Publications ; 2013
    In:  Neurorehabilitation and Neural Repair Vol. 27, No. 6 ( 2013-07), p. 561-574
    Details
    In: Neurorehabilitation and Neural Repair, SAGE Publications, Vol. 27, No. 6 ( 2013-07), p. 561-574
    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.
    Type of Medium: Online Resource
    ISSN: 1545-9683 , 1552-6844
    URL: Article
    DOI: 10.1177/1545968313481277
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
    detail.hit.zdb_id: 2100545-X
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