Neurotoxicity Research

, Volume 17, Issue 2, pp 114–129

Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson’s Disease

  • Rui D. S. Prediger
  • Aderbal S. AguiarJr.
  • Argelia Esperanza Rojas-Mayorquin
  • Claudia P. Figueiredo
  • Filipe C. Matheus
  • Laure Ginestet
  • Caroline Chevarin
  • Elaine Del Bel
  • Raymond Mongeau
  • Michel Hamon
  • Laurence Lanfumey
  • Rita Raisman-Vozari
Article

Abstract

Many studies have shown that deficits in olfactory and cognitive functions precede the classical motor symptoms seen in Parkinson’s disease (PD) and that olfactory testing may contribute to the early diagnosis of this disorder. Although the primary cause of PD is still unknown, epidemiological studies have revealed that its incidence is increased in consequence of exposure to certain environmental toxins. In this study, most of the impairments presented by C57BL/6 mice infused with a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1 mg/nostril) were similar to those observed during the early phase of PD, when a moderate loss of nigral dopamine neurons results in olfactory and memory deficits with no major motor impairments. Such infusion decreased the levels of the enzyme tyrosine hydroxylase in the olfactory bulb, striatum, and substantia nigra by means of apoptotic mechanisms, reducing dopamine concentration in different brain structures such as olfactory bulb, striatum, and prefrontal cortex, but not in the hippocampus. These findings reinforce the notion that the olfactory system represents a particularly sensitive route for the transport of neurotoxins into the central nervous system that may be related to the etiology of PD. These results also provide new insights in experimental models of PD, indicating that the i.n. administration of MPTP represents a valuable mouse model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Keywords

Parkinson’s disease Olfactory system Learning and memory Water maze MPTP Intranasal C57BL/6 mice 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Rui D. S. Prediger
    • 1
  • Aderbal S. AguiarJr.
    • 1
  • Argelia Esperanza Rojas-Mayorquin
    • 2
    • 3
    • 4
  • Claudia P. Figueiredo
    • 1
  • Filipe C. Matheus
    • 1
  • Laure Ginestet
    • 2
    • 3
    • 4
  • Caroline Chevarin
    • 5
  • Elaine Del Bel
    • 6
  • Raymond Mongeau
    • 5
  • Michel Hamon
    • 5
  • Laurence Lanfumey
    • 5
  • Rita Raisman-Vozari
    • 2
    • 3
    • 4
  1. 1.Departamento de Farmacologia, Centro de Ciências BiológicasUniversidade Federal de Santa Catarina, UFSCFlorianópolisBrazil
  2. 2.Université Pierre et Marie Curie-Paris 6Centre de Recherche de l’Institut du Cerveau et de la Moelle epiniere, UMR-S975ParisFrance
  3. 3.INSERM, U975ParisFrance
  4. 4.CNRS, UMR 7225ParisFrance
  5. 5.NeuropsychopharmacologieINSERM, UMR 677ParisFrance
  6. 6.Departamento MEF-Fisiologia, Faculdade de Odontologia de Ribeirão PretoUniversidade de São Paulo, USPRibeirão PretoBrazil

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