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Wiley, Journal of Neurochemistry, 2(136), p. 373-387, 2015

DOI: 10.1111/jnc.13409

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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Despite the different animal models of Parkinson's disease (PD) 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 PD, providing a better understanding of the pathophysiology of the disease and facilitating the testing of both protective and restorative treatments. This article is protected by copyright. All rights reserved.