کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2201355 1100012 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Matrix metalloproteinase-3 contributes to vulnerability of the nigral dopaminergic neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Matrix metalloproteinase-3 contributes to vulnerability of the nigral dopaminergic neurons
چکیده انگلیسی

Dopamine(DA)rgic neurons are particularly vulnerable due to the presence of oxidative stress-inducing molecules such as DA, tetrahydrobiopterin, iron and tyrosine hydroxylase (TH). We have recently observed that matrix metalloproteinase-3 (MMP-3) is involved in degeneration of DArgic neurons. In the present study, we sought to explore the role of MMP-3 in DArgic neurons not exposed to apparent stress conditions. In 8-week-old male mice deficient of MMP-3 gene (MMP-3 KO), the total number of DArgic neurons in the substantia nigra was considerably higher than wild type (WT). Primary cultured mesencephalic neurons from MMP-3 KO showed higher [3H]DA uptake capability compared to that of WT. The number of TH-immunopositive neurons and the length of average dendritic branch were also greater. This appeared to be selective for the DArgic system, because [3H]GABA uptake and calbindin D-28K and MAP-2 immunoreactivities were unaltered. On the other hand, no differences were noted in the levels of the striatal DA, DOPAC and BH4 and TH protein between the KO and WT. Interestingly, TH immunodensity per cell was lower in the DArgic neurons of MMP-3 KO both in primary culture and in vivo, suggesting the presence of a compensatory mechanism. These results further indicate a role of MMP-3 in the demise of DArgic neurons and suggest MMP-3 as a candidate cellular target for neuroprotective therapy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 56, Issue 1, January 2010, Pages 161–167
نویسندگان
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