Home » Key Scientific Articles » 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.

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.

Tristão FS, Amar M, Latrous I, Del-Bel EA, Prediger RD, Raisman-Vozari R.

Neurotox Res. 2014 Jan;25(1):24-32.

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

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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