Toxicity of MPTP on neurotransmission in three mouse models of Parkinson's disease

Pain, Stéphanie; Gochard, A.; Bodard, Sylvie; Gulhan, Zuhal; Prunier-Aesch, Caroline; Chalon, Sylvie

doi:10.1016/j.etp.2012.09.001

Cited by 34 publications

(18 citation statements)

References 40 publications

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“…Baseline values were obtained over multiple weeks before disease induction. Previous studies showed no effect of vehicle treatment [15,16,17], and all current animals showed stable baseline performance. Therefore, each monkey served as its own control.…”

Section: Methodsmentioning

confidence: 99%

Individual and Familial Susceptibility to MPTP in a Common Marmoset Model for Parkinson's Disease

et al. 2016

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Introduction: Insight into susceptibility mechanisms underlying Parkinson's disease (PD) would aid the understanding of disease etiology, enable target finding and benefit the development of more refined disease-modifying strategies. Methods: We used intermittent low-dose MPTP (0.5 mg/kg/week) injections in marmosets and measured multiple behavioral and neurochemical parameters. Genetically diverse monkeys from different breeding families were selected to investigate inter- and intrafamily differences in susceptibility to MPTP treatment. Results: We show that such differences exist in clinical signs, in particular nonmotor PD-related behaviors, and that they are accompanied by differences in neurotransmitter levels. In line with the contribution of a genetic component, different susceptibility phenotypes could be traced back through genealogy to individuals of the different families. Conclusion: Our findings show that low-dose MPTP treatment in marmosets represents a clinically relevant PD model, with a window of opportunity to examine the onset of the disease, allowing the detection of individual variability in disease susceptibility, which may be of relevance for the diagnosis and treatment of PD in humans.

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Section: Methodsmentioning

confidence: 99%

Individual and Familial Susceptibility to MPTP in a Common Marmoset Model for Parkinson's Disease

et al. 2016

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“…Recent studies have suggested that oxidative stress and abnormalities in the mitochondria can lead to increased free radical formation which might contribute to the pathogenesis of Parkinson's disease [2]. Administration of an exogenous neurotoxin called MPTP is also said to cause this disease due to selective loss of dopaminergic neurons in substantia nigra [3]. The main aim of drug therapy in Parkinsonism is to provide symptomatic relief to the patient by use of drugs that can restore the dopaminergic and cholinergic balance that is disturbed in this case.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Activities of Ropinirole and Pramipexole Novel Drugs Used in Treatment of Parkinsonism: An in Vitro Approach

Selva¹,

Vengadassalapathy²

2016

Asian J Pharm Clin Res

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Objective: The objective of this study is to evaluate and compare the free radical scavenging activities of selective dopamine agonist namely ropiniroleand pramipexole.Methods: The antioxidant activity of ropinirole and pramipexole at various concentrations was done by 1, 1-diphenyl-2picrylhydrazyl (DPPH) freeradical scavenging assay comparing it with ascorbic acid which was taken as standard.Results: The free radical scavenging property as measured by DPPH method showed that ropinirole and pramipexole have got a potent free radicalscavenging activity with that of ascorbic acid.Conclusion: Novel drugs such as pramipexole and ropinirole are promising molecules in the field of oxidative damage related neurodegenerativedisorders providing us an optimistic targeted approach toward neuroprotection.Keywords: Free radical scavenging, 1, 1-diphenyl-2picrylhydrazyl assay, Anti-Parkinson’s, Dopamine agonist.

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“…However, due to the difficulty of measuring DA in hippocampus and the question of which region was studied, the effects are controversial. Some studies found no decrease in DA levels after MPTP administration20 while others showed a depletion after multiple MPTP injections2122. Despite this uncertainty, MPTP intoxication has been shown to impair several types of memory and also damages synaptic transmission in mice2223.…”

mentioning

confidence: 99%

Pramipexole restores depressed transmission in the ventral hippocampus following MPTP-lesion

Castro-Hernández

Adlard

Finkelstein

2017

Sci Rep

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The hippocampus has a significant association with memory, cognition and emotions. The dopaminergic projections from both the ventral tegmental area and substantia nigra are thought to be involved in hippocampal activity. To date, however, few studies have investigated dopaminergic innervation in the hippocampus or the functional consequences of reduced dopamine in disease models. Further complicating this, the hippocampus exhibits anatomical and functional differentiation along its dorso-ventral axis. In this work we investigated the role of dopamine on hippocampal long term potentiation using D-amphetamine, which stimulates dopamine release, and also examined how a dopaminergic lesion affects the synaptic transmission across the anatomic subdivisions of the hippocampus. Our findings indicate that a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine induced dopaminergic lesion has time-dependent effects and impacts mainly on the ventral region of the hippocampus, consistent with the density of dopaminergic innervation. Treatment with a preferential D3 receptor agonist pramipexole partly restored normal synaptic transmission and Long-Term Potentiation. These data suggest a new mechanism to explain some of the actions of pramipexole in Parkinson´s disease.

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Toxicity of MPTP on neurotransmission in three mouse models of Parkinson's disease

Cited by 34 publications

References 40 publications

Individual and Familial Susceptibility to MPTP in a Common Marmoset Model for Parkinson's Disease

Individual and Familial Susceptibility to MPTP in a Common Marmoset Model for Parkinson's Disease

Antioxidant Activities of Ropinirole and Pramipexole Novel Drugs Used in Treatment of Parkinsonism: An in Vitro Approach

Pramipexole restores depressed transmission in the ventral hippocampus following MPTP-lesion

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