Document Detail


Limited remyelination in Theiler's murine encephalomyelitis due to insufficient oligodendroglial differentiation of nerve/glial antigen 2 (NG2)-positive putative oligodendroglial progenitor cells.
MedLine Citation:
PMID:  18466224     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Limited remyelination is a key feature of demyelinating Theiler's murine encephalomyelitis (TME). It is hypothesized that a dysregulation of differentiation of oligodendroglial progenitor cells (OPCs) represents the main cause of insufficient regeneration in this model of multiple sclerosis. METHODS: TME virus (TMEV)-infected SJL/J mice were evaluated by footprint analysis, light and electron microscopy, immunohistology, confocal immunofluorescence and RT-qPCR at multiple time points ranging from 1 h to 196 days post infection (dpi). RESULTS: Footprint analysis revealed a significantly decreased stride length at 147 and 196 dpi. Demyelination progressively increased from 14 towards 196 dpi. A mild amount of remyelination was detected at 147 and 196 dpi. Early onset axonal injury was detected from 14 dpi on. TMEV RNA was detectable throughout the observation period and markedly increased between 7 and 28 dpi. Intralesional nerve/glial antigen 2 (NG2)-positive OPCs were temporarily increased between 28 and 98 dpi. Similarly, a transient upregulation of NG2 and platelet-derived growth factor alpha-receptor mRNA was noticed. In contrast, intralesional 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-positive oligodendrocytes were decreased between 56 and 196 dpi. Although CNPase mRNA remained unchanged, myelin basic protein mRNA and especially its exon 2 containing splice variants were decreased. Glial fibrillary acidic protein (GFAP)-positive astrocytes and GFAP mRNA were increased in the late phase of TME. A mildly increased colocalization of both NG2/CNPase and NG2/GFAP was revealed at 196 dpi. CONCLUSIONS: Summarized, the present results indicated a dysregulation of OPC maturation as the main cause for the delayed and limited remyelination in TME. A shift of OPC differentiation from oligodendroglial towards astrocytic differentiation is postulated.
Authors:
R Ulrich; F Seeliger; M Kreutzer; P-G Germann; W Baumgärtner
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Publication Detail:
Type:  Journal Article     Date:  2008-05-05
Journal Detail:
Title:  Neuropathology and applied neurobiology     Volume:  34     ISSN:  1365-2990     ISO Abbreviation:  Neuropathol. Appl. Neurobiol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-01-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7609829     Medline TA:  Neuropathol Appl Neurobiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  603-20     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg, Hannover, Germany. reiner.ulrich@tiho-hannover.de
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MeSH Terms
Descriptor/Qualifier:
2',3'-Cyclic-Nucleotide Phosphodiesterases / genetics,  metabolism
Animals
Antigens / genetics,  metabolism*
Cardiovirus Infections / pathology,  physiopathology*,  virology
Cell Differentiation
Encephalomyelitis / pathology,  physiopathology*,  virology
Female
Gene Expression
Immunohistochemistry
Mice
Microscopy, Confocal
Microscopy, Electron
Microscopy, Fluorescence
Multiple Sclerosis / pathology,  physiopathology*
Myelin Basic Proteins / genetics,  metabolism
Myelin Sheath / pathology,  physiology*
Nerve Tissue Proteins / genetics,  metabolism
Oligodendroglia / cytology,  physiology
Proteoglycans / genetics,  metabolism*
RNA, Messenger / genetics,  metabolism
Receptor, Platelet-Derived Growth Factor alpha / genetics,  metabolism
Spinal Cord / pathology,  physiopathology,  virology
Stem Cells / cytology*,  physiology
Theilovirus* / isolation & purification
Chemical
Reg. No./Substance:
0/Antigens; 0/Myelin Basic Proteins; 0/Nerve Tissue Proteins; 0/Proteoglycans; 0/RNA, Messenger; 0/chondroitin sulfate proteoglycan 4; 0/glial fibrillary astrocytic protein, mouse; EC 2.7.10.1/Receptor, Platelet-Derived Growth Factor alpha; EC 3.1.4.-/2',3'-Cyclic-Nucleotide Phosphodiesterases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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