| AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice. | |
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MedLine Citation:
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PMID: 21918553 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Brain inflammation is a double-edged sword. It is required for brain repair in acute damage, whereas chronic inflammation and autoimmune disorders are neuropathogenic. Certain proinflammatory cytokines and chemokines are closely related to cognitive dysfunction and neurodegeneration. Representative anti-inflammatory cytokines, such as interleukin (IL)-10, can suppress neuroinflammation and have significant therapeutic potentials in ameliorating neurodegenerative disorders such as Alzheimer's disease (AD). Here, we show that adeno-associated virus (AAV) serotype 2/1 hybrid-mediated neuronal expression of the mouse IL-10 gene ameliorates cognitive dysfunction in amyloid precursor protein+ presenilin-1 bigenic mice. AAV2/1 infection of hippocampal neurons resulted in sustained expression of IL-10 without its leakage into the blood, reduced astro/microgliosis, enhanced plasma amyloid-β peptide (Aβ) levels and enhanced neurogenesis. Moreover, increased levels of IL-10 improved spatial learning, as determined by the radial arm water maze. Finally, IL-10-stimulated microglia enhanced proliferation but not differentiation of primary neural stem cells in the co-culture system, whereas IL-10 itself had no effect. Our data suggest that IL-10 gene delivery has a therapeutic potential for a non-Aβ-targeted treatment of AD.Gene Therapy advance online publication, 15 September 2011; doi:10.1038/gt.2011.126. |
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Authors:
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T Kiyota; K L Ingraham; R J Swan; M T Jacobsen; S J Andrews; T Ikezu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-15 |
Journal Detail:
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Title: Gene therapy Volume: - ISSN: 1476-5462 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, USA [2] Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA. |
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