Gene expression analysis in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model of Parkinson's disease using cDNA microarray: effect of R-apomorphine.
To establish the possible roles of oxidative stress, inflammatory processes and other unknown mechanisms in neurodegeneration, we investigated brain gene alterations in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of Parkinson's disease using Atlas mouse cDNA expression array membrane. The expression of 51 different genes involved in oxidative stress, inflammation, glutamate and neurotrophic factors pathways as well as in still undefined processes, such as cell cycle regulators and signal transduction molecules, was differentially affected by the treatment. The present study indicates the involvement of an additional cascade of events that might act in parallel to oxidative stress and inflammation to converge eventually into a common pathway leading to neurodegeneration. The attenuation of these gene changes by R-apomorphine, an iron chelator-radical scavenger drug, supports our previous findings in vivo where R-apomorphine was neuroprotective.
Grünblatt
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E
Technion Faculty of Medicine, Eve Topf and US National Parkinson's Foundation Centers for Neurodegenerative Diseases, Department of Pharmacology, Haifa, Israel.
Mandel
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S
Maor
G
G
Youdim
M B
MB
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D018076:DNA, Complementary / Q000235:genetics; D015259:Dopamine Agents; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000978:Antiparkinson Agents; D018076:DNA, Complementary; D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine