Persistent penetration of MPTP through the nasal route induces Parkinson's disease in mice

Authors

  • Ana I. Rojo,

    1. Instituto de Investigaciones Biomédicas and Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain
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  • Celia Montero,

    1. Instituto de Investigaciones Biomédicas and Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain
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  • María Salazar,

    1. Instituto de Investigaciones Biomédicas and Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain
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  • Ryan M. Close,

    1. Department of Neurology, Columbia University, New York 10032, USA
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  • Javier Fernández-Ruiz,

    1. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, 28040-Madrid, Spain
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  • Miguel A. Sánchez-González,

    1. Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain
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  • María Rosa De Sagarra,

    1. Instituto de Investigaciones Biomédicas and Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain
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  • Vernice Jackson-Lewis,

    1. Department of Neurology, Columbia University, New York 10032, USA
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  • Carmen Cavada,

    1. Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain
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  • Antonio Cuadrado

    1. Instituto de Investigaciones Biomédicas and Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain
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Dr Antonio Cuadrado, as above.
E-mail: antonio.cuadrado@uam.es

Abstract

The aetiology of idiopathic Parkinson's disease (PD) is poorly defined but environmental aggressions may be relevant. Here, we report a new model of PD in mice, based on chronic inoculation with neurotoxins in the nasal cavity, which is a natural route of contact with the environment. C57BL/6 mice, submitted to daily intranasal inoculation with MPTP for 30 days, developed motor deficits that correlated with a progressive and severe depletion of striatal dopamine levels, and loss of tyrosine hydroxylase and dopamine transporter staining in substantia nigra and striatum. Moreover, mice intranasally inoculated with MPTP developed strong astrogliosis and microgliosis in substantia nigra and striatum. Consistent with these observations, a role for oxidant aggression was demonstrated by increased levels of Mn-superoxide dismutase. However, α-synuclein aggregation was not observed. This new animal model provides a new tool for studying PD symptoms that develop slowly over time, and it may be used to asses risk from environmental neurotoxins.

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