| Interleukin-34 Selectively Enhances the Neuroprotective Effects of Microglia to Attenuate Oligomeric Amyloid-β Neurotoxicity. | |
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MedLine Citation:
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PMID: 21872563 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Microglia, macrophage-like resident immune cells in the brain, possess both neurotoxic and neuroprotective properties and have a critical role in the development of Alzheimer's disease (AD). We examined the function of IL-34, a newly discovered cytokine, on microglia because it reportedly induces proliferation of monocytes and macrophages,. We observed that the neuronal cells primarily produce IL-34 and that microglia express its receptor, colony-stimulating factor 1 receptor. IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-β (oAβ), which mediates synaptic dysfunction and neuronal damage in AD. IL-34 increased the expression of insulin-degrading enzyme, aiding the clearance of oAβ, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules. Consequently, microglia treated with IL-34 attenuated oAβ neurotoxicity in primary neuron-microglia co-cultures. In vivo, intracerebroventricular administration of IL-34 ameliorated impairment of associative learning and reduced oAβ levels through up-regulation of insulin-degrading enzyme and heme oxygenase-1 in an APP/PS1 transgenic mouse model of AD. These findings support the idea that enhancement of the neuroprotective property of microglia by IL-34 may be an effective approach against oAβ neurotoxicity in AD. |
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Authors:
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Tetsuya Mizuno; Yukiko Doi; Hiroyuki Mizoguchi; Shijie Jin; Mariko Noda; Yoshifumi Sonobe; Hideyuki Takeuchi; Akio Suzumura |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-25 |
Journal Detail:
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Title: The American journal of pathology Volume: - ISSN: 1525-2191 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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