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MPTP, MPDP+ and MPP+ cause decreases in dopamine content in mouse brain slices
J A Wilson1, T J Doyle, Y S Lau
1Department of Physiology, Creighton University School of Medicine, Omaha, NE 68178.
Abstract:
MPTP causes a Parkinson's disease-like syndrome in which the dopamine content of the nigrostriatal system decreases. We have studied the relationship between physiological changes and dopamine content using a brain slice preparation developed for electrophysiological studies of corticostriate and nigrostriatal synaptic transmission. We report that MPTP, MPDP+ and MPP+ cause significant decreases in dopamine content of mouse brain slices. We also report that compounds (pargyline and GBR-12909) which block MPTP's toxicity in vivo and prevent non-reversible changes in synaptic transmission are not able to alter MPTP's ability to decrease slice dopamine contents. This indicates that the dopamine content in slices may not be causally related to the non-reversible decrease in synaptic transmission or in vivo neurotoxicity.
Insights
MPTP neurotoxicity causes Parkinson's-like symptoms by decreasing dopamine. However, this study found that dopamine levels in brain slices may not directly cause the irreversible synaptic changes or toxicity seen in vivo.
Area of Science:
- Neuroscience
- Pharmacology
- Neurodegenerative Diseases
Background:
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces a Parkinson's disease-like syndrome.
- MPTP exposure leads to a reduction in dopamine levels within the nigrostriatal system.
Purpose of the Study:
- To investigate the relationship between physiological changes and dopamine content in the context of MPTP-induced neurotoxicity.
- To determine if dopamine content in brain slices is causally linked to MPTP's in vivo neurotoxicity and synaptic transmission alterations.
Main Methods:
- Utilized a mouse brain slice preparation for electrophysiological studies of corticostriate and nigrostriatal synaptic transmission.
- Measured dopamine content in brain slices after exposure to MPTP, MPDP+, and MPP+.
- Assessed the effect of neuroprotective compounds (pargyline and GBR-12909) on MPTP's ability to decrease dopamine content in slices.
Main Results:
- MPTP, MPDP+, and MPP+ significantly reduced dopamine content in mouse brain slices.
- Compounds known to block MPTP's in vivo toxicity and prevent irreversible synaptic changes did not affect MPTP's capacity to deplete dopamine in slices.
Conclusions:
- The decrease in dopamine content observed in brain slices after MPTP exposure may not be the primary cause of the irreversible synaptic transmission deficits or the in vivo neurotoxicity associated with MPTP.
- These findings suggest a dissociation between acute dopamine depletion in slices and the long-term neurotoxic effects of MPTP.