Journal
NEUROTOXICITY RESEARCH
Volume 25, Issue 1, Pages 24-32Publisher
SPRINGER
DOI: 10.1007/s12640-013-9401-8
Keywords
Parkinson's disease; MPTP; Subacute; Intranasal; Neurodegeneration; Neuroinflammation
Categories
Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Programa Ciencia sem Fronteiras (CsF)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- CAPES-COFECUB (France/Brazil) [681/2010]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP
- thematic project) [2012/17626-7]
- FAPESP/INSERM [2008/55092-9]
- Fundacao de Apoio a Pesquisa Cientifica e Tecnologica do Estado de Santa Catarina (FAPESC)
- CNPq, Brazil
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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 (similar to 80 %) and moderate (similar to 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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