| Inflammation induced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demyelination. | |
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MedLine Citation:
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PMID: 20532539 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Primary loss and dysfunction of astrocytes may trigger demyelination, as seen in neuromyelitis optica, an inflammatory disease of the central nervous system. In most patients affected by this disease, injury to astrocytes is initiated by the action of autoantibodies targeting aquaporin 4 (AQP-4), a water channel on astrocytes. We show here that damage of astrocytes and subsequent demyelination can also occur in the absence of autoantibody-mediated mechanisms. Following injection of lipopolysaccharide into the white matter initial microglia activation is followed by a functional disturbance of astrocytes, mainly reflected by retraction of astrocytic foot processes at the glia limitans and loss of AQP-4 and connexins, which are involved in the formation of gap junctions between astrocytes and oligodendrocytes. Demyelination and oligodendrocyte degeneration in this model follows astrocyte pathology. Similar structural abnormalities were also seen in a subset of active lesions in multiple sclerosis. Our studies suggest that astrocyte injury may be an important early step in the cascade of lesion formation in brain inflammation. |
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Authors:
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Rakhi Sharma; Marie-Therese Fischer; Jan Bauer; Paul A Felts; Kenneth J Smith; Tatsuro Misu; Kazuo Fujihara; Monika Bradl; Hans Lassmann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-08 |
Journal Detail:
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Title: Acta neuropathologica Volume: 120 ISSN: 1432-0533 ISO Abbreviation: Acta Neuropathol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-06-28 Completed Date: 2010-09-28 Revised Date: 2011-04-06 |
Medline Journal Info:
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Nlm Unique ID: 0412041 Medline TA: Acta Neuropathol Country: Germany |
Other Details:
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Languages: eng Pagination: 223-36 Citation Subset: IM |
Affiliation:
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Centre for Brain Research, Medical University of Vienna, Vienna, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aquaporin 4 / metabolism Astrocytes / immunology*, pathology Cells, Cultured Central Nervous System / pathology* Coculture Techniques / methods Disease Models, Animal Encephalomyelitis, Autoimmune, Experimental* / etiology, immunology, pathology Gene Expression Regulation / drug effects, immunology Humans Immunity, Innate* Membrane Proteins / metabolism Microscopy, Confocal / methods Multiple Sclerosis / immunology, pathology* Nerve Tissue Proteins / metabolism Neuroglia / drug effects Polysaccharides / pharmacology Rats Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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P 19854-B02//Austrian Science Fund FWF; P 21581-B09//Austrian Science Fund FWF |
| Chemical | |
Reg. No./Substance:
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0/AQP4 protein, human; 0/Aquaporin 4; 0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/Polysaccharides |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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