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Evaluation of Nigrostriatal Neurodegeneration and Neuroinflammation Following Repeated Intranasal 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Administration in Mice, an Experimental Model of Parkinson’s Disease

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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting approximately 1 % of the population older than 60 years. The administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice is the most widely used approach to elucidate the mechanisms of cell death involved in PD. However, the magnitude of the PD-like neurodegeneration induced by MPTP depends on many variables, including the regimen of its administration. It has been demonstrated that intranasal (i.n.) administration of MPTP constitutes a new route of toxin delivery to the brain that mimics environmental exposure to neurotoxins. Previous data showed that mice submitted to chronic and acute i.n. MPTP treatment displayed a robust (~80 %) and moderate (~55 %) loss of striatal dopamine, respectively. However, little is known about the neurodegenerative and neuroinflammatory processes following a subacute i.n. MPTP administration in mice. Here, the C57BL/6 mice were infused intranasally with MPTP (1 mg/nostril/day) during 4 consecutive days. At 7 and 28 days after the last administration, the subacute i.n. MPTP regime decreased the tyrosine hydroxylase (TH)-labeling in the striatum (40–50 %) and substantia nigra (25–30 %) and increased the astrogliosis in such brain areas at both time points. Taken together, our data showed that the subacute administration of MPTP into the nasal cavity of C57BL/6 mice induces long-lasting neurodegeneration and neuroinflammation in the nigrostriatal pathway, thus representing a valuable animal model for the investigation of neuroprotective strategies in PD.

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Acknowledgments

The authors gratefully thank the financial support and grants provided by the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Programa Ciência sem Fronteiras (CsF), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), CAPES-COFECUB (France/Brazil; 681/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; thematic project 2012/17626-7), FAPESP/INSERM (2008/55092-9), and Fundação de Apoio à Pesquisa Científica e Tecnológica do Estado de Santa Catarina (FAPESC). E.A.D.B. and R.D.P. are supported by research fellowships from CNPq, Brazil.

Conflict of interest

The authors have no financial or personal conflicts of interest related to this study.

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Authors and Affiliations

  1. INSERM, UMR 975, CRICM, Thérapeutique Expérimentale de la Neurodégénérescence, Paris, France

    Fabrine S. M. Tristão, Majid Amar, Ines Latrous & Rita Raisman-Vozari

  2. Departamento MEF - Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, Brazil

    Elaine A. Del-Bel

  3. Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina (UFSC), Campus Trindade, Florianópolis, SC, Brazil

    Rui D. Prediger

  4. Faculté de Médecine, Université Pierre-et-Marie-Curie, Paris, France

    Rita Raisman-Vozari

  5. CNRS, UMR, 7225, Paris, France

    Rita Raisman-Vozari

  6. Hôpital de la Salpêtrière/Institut du cerveau et de la moelle épinière, 47 boulevard de l’Hôpital, 75651, Paris, Cedex 13, France

    Rita Raisman-Vozari

  7. Núcleo de Apoio à Pesquisa em Neurociência Aplicada (NAPNA), Universidade de São Paulo (USP), São Paulo, Brazil

    Elaine A. Del-Bel

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  1. Fabrine S. M. Tristão
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  2. Majid Amar
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  3. Ines Latrous
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Correspondence to Rita Raisman-Vozari.

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Tristão, F.S.M., Amar, M., Latrous, I. et al. Evaluation of Nigrostriatal Neurodegeneration and Neuroinflammation Following Repeated Intranasal 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Administration in Mice, an Experimental Model of Parkinson’s Disease. Neurotox Res 25, 24–32 (2014). https://doi.org/10.1007/s12640-013-9401-8

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