cDNA microarray to study gene expression of dopaminergic neurodegeneration and neuroprotection in MPTP and 6-hydroxydopamine models: implications for idiopathic Parkinson's disease.
cDNA microarray membranes comprising 1,200 different gene fragments have been employed to identify gene expression profile in MPTP-induced nigro striatal dopamine neurodegeneration and its protection with Rapomorphine. Both MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and R-apomorphine (R-APO) induced alterations in specific patterns of gene expression. MPTP altered the expression of 49 different genes involved in oxidative stress (oxidative stress-induced protein A 170, cytochrome P450 1A1 and Osp94), inflammation (cytotoxic cytokines, eg: IL-1, IL-6, TNF-alpha), protective cytokines (IL-10), glutamate receptors (NMDA but not AMPA receptors), neurotrophic factors (GDNF, EGF), nitric oxide synthase and transferrin receptor, as determined by microarray membrane hybridization. Furthermore, an additional cascade of further, yet undefined events, also occurred (cell cycle regulators and signal transduction factors), that might act in parallel to oxidative stress (OS) and inflammation, to converge eventually into a common pathway leading to neurodegeneration. R-APO, previously shown by us to protect against MPTP neurotoxicity, prevented the over expression of several genes known to participate in cell death. cDNA microarrays will provide new prospects to study and identify various mechanism of neurodegeneration and neuroprotection not feasible with conventional biochemical procedures, as well as new prospects to develop effective neuroprotective drugs.
Mandel
S
S
Department of Pharmacology, Eve Topf and US National Parkinson's Foundation Centers for Neurodegenerative Diseases, Bruce Rappaport Family Research Institute, Technion--Faculty of Medicine, Haifa, Israel.
Grünblatt
E
E
Youdim
M
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000378:metabolism
D018696:Neuroprotective Agents; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine