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TLR4 and inflammatory response to neuronal degeneration.

Authors
Konat-GW; Sriram-K; Kraszpulski-M; O'Callaghan-JP
Source
J Neurochem 2007 Aug; 102(Suppl 1):137-138
NIOSHTIC No.
20032695
Abstract
Toll-like receptor 4 (TLR4) has recently emerged as an important mediator of inflammatory responses elicited by molecules released from injured tissues. The present study was undertaken to determine the role of TLR4 in such responses following neuronal damage. Striatal dopaminergic neurodegeneration was induced in TLR4-mutant and control mice by a single subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). In both groups, the level of tyrosine hydroxylase (TH) in the striatum decreased within 72 h by B50% as compared with untreated animals indicating extensive neuronal damage. The loss of TH was associated with glial activation as seen from the up-regulation of GFAP, which was similar in both groups. The phosphorylation of STAT3, a key mediator of astrogliosis, was also increased. Moreover, the expression of glia-derived cytokines, i.e., TNFa, MCP-1 and LIF, was profoundly up-regulated in both mutant and control striata. Interestingly, basal expression of MCP-1 and LIF in TLR4-mutants was approximately five fold higher than in controls. These results indicate that TLR4 does not mediate inflammatory responses associated with dopaminergic neurodegeneration. However, the receptor seems to be involved in controlling basal expression of certain inflammatory genes.
Keywords
Tissue-disorders; Genetics; Genotoxicity; Genotoxic-effects; Genes; Gene-mutation; Laboratory-animals; Animal-studies; Animals; Neuromotor-disorders; Neuromuscular-system-disorders
Contact
NIOSH, CDCP, 1095 Willowdale Rd, MS 2800, Morgantown, WV 26505
CODEN
JONRA9
Publication Date
20070901
Document Type
Journal Article
Fiscal Year
2007
NTIS Accession No.
NTIS Price
ISSN
0022-3042
NIOSH Division
HELD
Source Name
Journal of Neurochemistry
State
WV
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