Publication:
Chronic and progressive Parkinson's disease MPTP model in adult and aged mice.

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Date

2016-01-11

Authors

Muñoz-Manchado, Ana B
Villadiego, Javier
Romo-Madero, Sonia
Suarez-Luna, Nela
Bermejo-Navas, Alfonso
Rodriguez-Gomez, Jose A
Garrido-Gil, Pablo
Labandeira-Garcia, Jose L
Echevarria, Miriam
Lopez-Barneo, Jose

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Wiley-Blackwell Publishing Ltd.
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Abstract

Despite the different animal models of Parkinson's disease developed during the last years, they still present limitations modelling the slow and progressive process of neurodegeneration. Here, we undertook a histological, neurochemical and behavioural analysis of a new chronic parkinsonian mouse model generated by the subcutaneous administration of low doses of MPTP (20 mg/kg, 3 times per week) for 3 months, using both young adult and aged mice. The MPTP-induced nigrostriatal neurodegeneration was progressive and was accompanied by a decrease in striatal dopamine levels and motor impairment. We also demonstrated the characteristic neuroinflammatory changes (microglial activation and astrogliosis) associated with the neurodegenerative process. Aged animals showed both a faster time course of neurodegeneration and an altered neuroinflammatory response. The long-term systemic application of low MPTP doses did not induce any increase in mortality in either young adult or aged mice and better resembles the slow evolution of the neurodegenerative process. This treatment could be useful to model different stages of Parkinson's disease, providing a better understanding of the pathophysiology of the disease and facilitating the testing of both protective and restorative treatments.

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MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Age Factors
Aging
Animals
Catecholamines
Chronic Disease
Corpus Striatum
Disease Models, Animal
Disease Progression
Dose-Response Relationship, Drug
Inflammation
MPTP Poisoning
Mice
Mice, Inbred C57BL
Motor Activity
Muscle Strength
Nerve Degeneration
Nerve Tissue Proteins
Psychomotor Performance
Tyrosine 3-Monooxygenase

DeCS Terms

Anciano
Terapéutica
Enfermedad de Parkinso
Dopamina
Mortalidad
Gliosis
Tiempo

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Keywords

MPTP, Parkinson's disease, ageing, animal models, dopamine, neuroinflammation

Citation

Muñoz-Manchado AB, Villadiego J, Romo-Madero S, Suárez-Luna N, Bermejo-Navas A, Rodríguez-Gómez JA, et al. Chronic and progressive Parkinson's disease MPTP model in adult and aged mice. J Neurochem. 2016 Jan;136(2):373-87.