1. Individual and Familial Susceptibility to MPTP in a Common Marmoset Model for Parkinson's Disease
- Author
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August B. Smit, Sam O. Hofman, Ronald E. van Kesteren, Sigrid K. Franke, Jacqueline Wubben, Ingrid H.C.H.M. Philippens, Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, and Amsterdam Neuroscience - Neurodegeneration
- Subjects
Male ,0301 basic medicine ,Parkinson's disease ,Tyrosine 3-Monooxygenase ,Substantia nigra ,Disease ,Motor Activity ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Neurochemical ,Parkinsonian Disorders ,biology.animal ,Journal Article ,medicine ,Animals ,Genetic Predisposition to Disease ,Neurotransmitter ,biology ,Dopaminergic Neurons ,MPTP ,Marmoset ,Callithrix ,Parkinson Disease ,biology.organism_classification ,medicine.disease ,Corpus Striatum ,Substantia Nigra ,Disease Models, Animal ,030104 developmental biology ,Neurology ,chemistry ,1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ,Female ,Neurology (clinical) ,Psychology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2016
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