Increased MMP-3 and CTGF expression during lipopolysaccharide-induced dopaminergic neurodegeneration.
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.
McClain
Justin A
JA
Virginia Commonwealth University, Department of Physiology and Biophysics, United States.
Phillips
Linda L
LL
Fillmore
Helen L
HL
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D008070:Lipopolysaccharides; D055513:Connective Tissue Growth Factor; D014446:Tyrosine 3-Monooxygenase; D019278:Matrix Metalloproteinase 3