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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
MPDP+ causes a non-reversible decrease in neostriatal synaptic transmission in mouse brain slice
J A Wilson1, J S Wilson, F F Weight
1Laboratory of Preclinical Studies, National Institute on Alcohol, Abuse and Alcoholism, Rockville, MD 20852.
Abstract:
MPTP causes a Parkinson's disease-like syndrome in man and certain other animals. The toxic effect occurs if monoamine oxidase B is available, indicating that an MPTP metabolite may cause the toxic effect. We tested the effect of MPDP+, the first product of MPTP oxidation, and found that it, like MPTP, caused a non-reversible decrease in synaptic transmission in the mouse brain slice preparation. As the second oxidation product, MPP+ had been shown not to cause a similar, non-reversible decrease in synaptic transmission, MPDP+ is a better candidate for the role of toxic substance.
Insights
MPTP causes Parkinson's-like symptoms. Researchers found that MPDP+, an MPTP metabolite, causes non-reversible synaptic transmission decrease, suggesting it is the toxic agent.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces Parkinsonism.
- Monoamine oxidase B (MAO-B) is necessary for MPTP's toxicity, suggesting a metabolite is responsible.
Purpose of the Study:
- To identify the specific MPTP metabolite responsible for its neurotoxic effects.
- To compare the neurotoxic potential of MPDP+ and MPP+.
Main Methods:
- Utilized mouse brain slice preparations.
- Assessed the effect of MPTP metabolites on synaptic transmission.
Main Results:
- MPTP and its first oxidation product, MPDP+, caused a non-reversible decrease in synaptic transmission.
- MPP+, the second oxidation product, did not cause a similar effect.
Conclusions:
- MPDP+ is a more likely candidate than MPP+ for the neurotoxic substance causing MPTP-induced Parkinsonism.
- This finding clarifies the mechanism of MPTP neurotoxicity.
