| Fluoxetine protects neurons against microglial activation-mediated neurotoxicity. | |
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MedLine Citation:
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PMID: 22166439 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Neuroinflammation is closely associated with the pathogenesis of Parkinson's disease (PD) and other neurological disorders. Increasing evidence suggests that inhibition of microglia-mediated neuroinflammation might represent a promising therapeutic potential for PD and related disorders. Fluoxetine, a selective serotonin reuptake inhibitor, is commonly used for the treatment of major depression due to its tolerability and safety profiles. Recent studies have shown that fluoxetine affords robust neuroprotection in a series of neurological disease models. However, the mechanism underlying fluoxetine-mediated neuroprotection remains unclear. Here, by using rat primary midbrain neuronglia cultures, we report that both R and S enantiomers of fluoxetine attenuated chronic neurodegeneration induced by a common inflammogen lipopolysaccharide (LPS) and a neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)). Reconstituted cell culture studies further revealed that microglia were required for fluoxetine-mediated neuroprotection. Fluoxetine significantly inhibited LPS-induced activation of microglia and subsequent release of multiple pro-inflammatory and cytotoxic factors including tumor necrosis factor-α, interleukin-1β, nitric oxide, and reactive oxygen species. Furthermore, inhibition of microglial NF-κB signaling pathway participated in fluoxetine-mediated neuroprotection. Collectively, fluoxetine exerted neuroprotection against microglia-mediated neurotoxicity. Thus, fluoxetine might hold a potential to retard inflammation-mediated chronic neurodegenerative process of PD. |
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Authors:
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Feng Zhang; Hui Zhou; Belinda C Wilson; Jing-Shan Shi; Jau-Shyong Hong; Hui-Ming Gao |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Parkinsonism & related disorders Volume: 18 Suppl 1 ISSN: 1873-5126 ISO Abbreviation: Parkinsonism Relat. Disord. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9513583 Medline TA: Parkinsonism Relat Disord Country: England |
Other Details:
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Languages: eng Pagination: S213-7 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Neuropharmacology Section, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA; Department of Pharmacology and Key Lab of Basic Pharmacology of Guizhou, Zunyi Medical College, Zunyi 563003, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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