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Alteration of pallidal cholinergic activity in MPTP-treated monkeys: effect of dihydro-alpha-ergocryptine (DEK)
1Institute of Pharmacology, Faculty of Sciences, University of Pavia, Italy.
Abstract:
Monkeys, intravenously administered with MPTP at the dose of 0.3 mg/kg for 5 consecutive days, develop a severe Parkinson-like syndrome. Cholinergic enzyme activities are increased in the internal segment of the globus pallidus (GPi) and into a lesser extent in the external globus pallidus (GPe). Cholinergic activities are not significantly affected in the caudate and putamen nor in the frontal, parietotemporal, occipital cortices and in the cerebellum. The treatment of the animals twice daily for 2 weeks with dihydro-alpha-ergocryptine (DEK) starting 5 days before the first MPTP administration counteracts the neurotoxin-induced alteration in the internal pallidum and ameliorates some motor related parkinsonian symptoms.
Insights
MPTP administration in monkeys induced Parkinson-like symptoms and altered cholinergic enzyme activity in the globus pallidus. Dihydro-alpha-ergocryptine (DEK) treatment counteracted these neurotoxin-induced changes and improved motor deficits.
Area of Science:
- Neuroscience
- Pharmacology
- Neurology
Background:
- MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin that selectively destroys dopaminergic neurons, causing Parkinsonism.
- Parkinson's disease is characterized by motor deficits and neurochemical alterations, including changes in cholinergic activity.
Purpose of the Study:
- To investigate the effects of MPTP on cholinergic enzyme activity in specific brain regions of monkeys.
- To evaluate the potential therapeutic effects of dihydro-alpha-ergocryptine (DEK) in mitigating MPTP-induced Parkinsonism.
Main Methods:
- Monkeys were administered MPTP intravenously to induce a Parkinson-like syndrome.
- Cholinergic enzyme activities were measured in various brain regions, including the globus pallidus, caudate, putamen, and cortical areas.
- Animals were treated with dihydro-alpha-ergocryptine (DEK) before and during MPTP administration.
Main Results:
- MPTP administration led to a severe Parkinson-like syndrome in monkeys.
- Significant increases in cholinergic enzyme activities were observed in the internal (GPi) and external (GPe) globus pallidus.
- Cholinergic activities in other brain regions, including the caudate, putamen, and cortex, were not significantly affected.
- DEK treatment, initiated prior to MPTP exposure, counteracted the alterations in the internal pallidum and improved motor symptoms.
Conclusions:
- MPTP-induced Parkinsonism in monkeys is associated with specific alterations in globus pallidus cholinergic activity.
- Dihydro-alpha-ergocryptine (DEK) demonstrates neuroprotective potential by counteracting MPTP-induced neurochemical changes and ameliorating motor deficits.
- These findings suggest DEK as a potential therapeutic agent for Parkinson's disease.