MPTP causes a non-reversible depression of synaptic transmission in mouse neostriatal brain slice |
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| Authors: | John A. Wilson James S. Wilson Forrest F. Weight |
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| Affiliation: | 1. Laboratory of Preclinical Studies, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, U.S.A.;2. Department of Anatomy, School of Medicine, Howard University, Washington, DC 20059, U.S.A.;1. Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University, Frankfurt am Main, Germany;2. Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt am Main, Germany;1. Chair of Pharmacodynamics, Department of Pharmacodynamics, Jagiellonian University, Medical College, Kraków, Poland;2. Chair of Pharmaceutical Chemistry, Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, Kraków, Poland;3. Faculty of Production Engineering, Warsaw University of Life Sciences, Warszawa, Poland;1. Stem Cell Laboratory for CNS Disease Modeling, Wallenberg Neuroscience Center, Department of Experimental Medical Science, BMC A10, Lund University, 22184 Lund, Sweden;2. Strategic Research Area MultiPark, Lund University, 22184 Lund, Sweden;3. Lund Stem Cell Center, Lund University, 22184 Lund, Sweden;4. Experimental Neuroinflammation Laboratory, Department of Experimental Medical Science, BMC B11, Lund University, 22184 Lund, Sweden;5. Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;6. Parkinson Institute, Istituti Clinici di Perfezionamento, 20126 Milan, Italy |
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| Abstract: | MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes a Parkinson's disease-like syndrome. The mechanism of MPTP's neurotoxicity is unknown; however, one hypothesis is that MPP+ (1-methyl-4-phenylpyridinium), a product of MPTP's oxidation, is the neurotoxic agent. Using a mouse brain slice preparation we studied the effects of MPTP and MPP+ on synaptic transmission. We found MPTP caused a decrease in amplitude of an excitatory synaptic response not reversed by washing. This non-reversible action of MPTP was prevented by GBR-32 and pargyline. MPP+s caused a decrease in synaptic transmission, but this decrease was reversed by washing. The results suggest that the toxic effect of MPTP on synaptic transmission is not accounted for by the action of MPP+. |
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| Keywords: | 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1-methyl-4-phenylpyridinium brain slice synaptic transmission toxicity |
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