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The action of MPTP on synaptic transmission is affected by changes in Ca2+ concentrations
J A Wilson1, Y S Lau, J G Gleeson
1Division of Physiology, Creighton University School of Medicine, Omaha, NE 68178.
Abstract:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a disruption of nigrostriatal dopaminergic function which resembles parkinsonism. On the cellular level, the disruption involves a Ca2+ independent release of dopamine, depletion of nigral and striatal dopamine, and the death of dopaminergic neurons. We have previously reported that MPTP can cause a non-reversible inhibition of neostriatal synaptic transmission. In this study we investigated the effect of altering Ca2+ concentration on MPTP's actions in the mouse nigrostriatal brain slice. We report finding that the MPTP induced non-reversible decrease in N-2 amplitude did not occur if synaptic transmission had been blocked using a low Ca2(+)-high Mg2+ artificial cerebrospinal fluid (ACSF) during MPTP application. Low Ca2(+)-high Mg2+ ACSF did not however alter the decrease in slice dopamine content caused by MPTP. These data provide initial support for the hypothesis that MPTP's ability to alter functional synaptic transmission is Ca2+ dependent whereas its releasing action on dopamine is Ca2+ independent.
Insights
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) impairs brain function, mimicking Parkinson's disease. This study shows MPTP's effect on synaptic transmission is calcium-dependent, but dopamine release is not.
Area of Science:
- Neuroscience
- Neuropharmacology
- Cellular Biology
Background:
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces parkinsonism.
- MPTP disrupts nigrostriatal dopaminergic function, leading to dopamine depletion and neuronal death.
- Previous research indicated MPTP causes irreversible inhibition of neostriatal synaptic transmission.
Purpose of the Study:
- To investigate the role of calcium (Ca2+) concentration in MPTP's neurotoxic effects.
- To determine if Ca2+ influences MPTP-induced synaptic transmission changes and dopamine release.
Main Methods:
- Utilized mouse nigrostriatal brain slices.
- Applied MPTP in artificial cerebrospinal fluid (ACSF) with varying Ca2+ and Mg2+ concentrations.
- Measured N-2 amplitude to assess synaptic transmission and dopamine content.
Main Results:
- MPTP-induced non-reversible decrease in N-2 amplitude was prevented by blocking synaptic transmission with low Ca2+-high Mg2+ ACSF.
- Low Ca2+-high Mg2+ ACSF did not affect MPTP-induced decrease in slice dopamine content.
- MPTP's action on synaptic transmission appears Ca2+-dependent.
Conclusions:
- MPTP's disruption of synaptic transmission is calcium-dependent.
- MPTP's dopamine-releasing action is calcium-independent.
- These findings differentiate the mechanisms underlying MPTP's effects on synaptic function and dopamine release.