Spinal cord degeneration in C57BL/6N mice following induction of experimental parkinsonism with MPTP |
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Authors: | Samantaray Supriti Knaryan Varduhi H Butler Jonathan T Ray Swapan K Banik Naren L |
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Institution: | Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA; Department of Neurohormones Biochemistry, H. Buniatian Institute of Biochemistry, National Academy of Sciences of the Republic of Armenia, Yerevan, Republic of Armenia |
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Abstract: | We examined neurodegeneration in spinal cord (SC) and role of such extra-nigral degeneration in MPTP-induced experimental parkinsonism in C57BL/6N mice. HPLC-photodiode array analysis confirmed presence of the active neurotoxin MPP+ in SC after single injection of MPTP (25 mg/kg, i.p.). Mitochondrial enzyme monoamine oxidase-B (MAO-B) responsible for in vivo conversion of MPTP to MPP+ was inhibited in SC by pre-treatment with l -deprenyl, a specific inhibitor of MAO-B. Besides in vitro conversion of MPTP to MPP+ occurred by SC mitochondrial preparation, which was inhibited by l -deprenyl implicating SC as a specific target of MPTP-neurotoxicity. Double immunofluorescent labeling and spectrofluorimetric assay via kynuramine oxidation showed MAO-B expression and activity in SC neurons. Localization of dopamine transporter immunoreactivity in SC along with specific uptake of 3H-MPP+ by SC synaptosomal preparation further confirmed SC as target of MPTP-neurotoxicity. Compared with control, increased neuronal death on the seventh day in SC of mice injected with MPTP (2 × 25 mg/kg, at 6 h interval) strongly suggested SC degeneration in pre-symptomatic phase of MPTP-induced experimental parkinsonism. Such extra-nigral neurodegeneration in Parkinson's disease indicated novel molecular mechanism preceding nigrostriatal degeneration and suggested designing broad therapeutic intervention for this complex movement disorder. |
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Keywords: | dopamine transporter experimental parkinsonism monoamine oxidase-B MPP+ Parkinson's disease spinal cord |
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