PMID- 19463894 OWN - NLM STAT- MEDLINE DCOM- 20090901 LR - 20090610 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 460 IP - 1 DP - 2009 Aug 21 TI - Increased MMP-3 and CTGF expression during lipopolysaccharide-induced dopaminergic neurodegeneration. PG - 27-31 LID - 10.1016/j.neulet.2009.05.044 [doi] AB - Accumulating evidence indicates that neuroinflammation contributes significantly to progressive dopaminergic (DA) neurodegeneration in Parkinson's disease (PD). Altered matrix metalloproteinase-3 (MMP-3) expression has been reported in several neuroinflammatory paradigms; however, its relationship to inflammation-induced DA neurotoxicity has not been explored. To this end, we investigated the temporal expression pattern of MMP-3 and one of its downstream targets, connective tissue growth factor (CTGF), following lipopolysaccharide (LPS)-induced DA neurodegeneration. LPS was directly injected into the substantia nigra of male Sprague-Dawley rats. Lesion formation was confirmed with immunohistochemistry 48 h post-injection. MMP-3 and CTGF were measured by western blot 12, 24, and 48 h post-injection. In association with neurodegeneration, MMP-3 expression and activation was significantly increased 24 and 48 h after LPS injection. In addition, CTGF expression increased 5-fold at the 24h time point. The temporal changes in MMP-3 and CTGF expression corresponded to the neurodegenerative phase of this model, suggesting that these two proteins may participate in neuroinflammation-induced DA neurotoxicity. FAU - McClain, Justin A AU - McClain JA AD - Virginia Commonwealth University, Department of Physiology and Biophysics, United States. FAU - Phillips, Linda L AU - Phillips LL FAU - Fillmore, Helen L AU - Fillmore HL LA - eng PT - Journal Article DEP - 20090520 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Lipopolysaccharides) RN - 139568-91-5 (Connective Tissue Growth Factor) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Brain/drug effects/metabolism/pathology MH - Connective Tissue Growth Factor/*metabolism MH - Disease Models, Animal MH - Lipopolysaccharides/*toxicity MH - Male MH - Matrix Metalloproteinase 3/*metabolism MH - Neurodegenerative Diseases/*chemically induced/*metabolism/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Time Factors MH - Tyrosine 3-Monooxygenase/metabolism MH - Up-Regulation/*drug effects EDAT- 2009/05/26 09:00 MHDA- 2009/09/02 06:00 CRDT- 2009/05/26 09:00 PHST- 2009/02/04 00:00 [received] PHST- 2009/03/27 00:00 [revised] PHST- 2009/05/15 00:00 [accepted] PHST- 2009/05/26 09:00 [entrez] PHST- 2009/05/26 09:00 [pubmed] PHST- 2009/09/02 06:00 [medline] AID - S0304-3940(09)00668-5 [pii] AID - 10.1016/j.neulet.2009.05.044 [doi] PST - ppublish SO - Neurosci Lett. 2009 Aug 21;460(1):27-31. doi: 10.1016/j.neulet.2009.05.044. Epub 2009 May 20.