ORIGINAL ARTICLE 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 Fabrine S. M. Trista ˜o • Majid Amar • Ines Latrous • Elaine A. Del-Bel • Rui D. Prediger • Rita Raisman-Vozari Received: 29 April 2013 / Accepted: 3 May 2013 Ó Springer Science+Business Media New York 2013 Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting approxi- mately 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 administra- tion. 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 fol- lowing 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 neurodegen- eration and neuroinflammation in the nigrostriatal pathway, thus representing a valuable animal model for the investi- gation of neuroprotective strategies in PD. Keywords Parkinson’s disease Á MPTP Á Subacute Á Intranasal Á Neurodegeneration Á Neuroinflammation Introduction Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting approximately 1 % of the population older than F. S. M. Trista ˜o Á M. Amar Á I. Latrous Á R. Raisman-Vozari INSERM, UMR 975, CRICM, The ´rapeutique Expe ´rimentale de la Neurode ´ge ´ne ´rescence, Paris, France E. A. Del-Bel Departamento MEF - Fisiologia, Faculdade de Odontologia de Ribeira ˜o Preto, Universidade de Sa ˜o Paulo (USP), Ribeira ˜o Preto, Brazil E. A. Del-Bel Nu ´cleo de Apoio a ` Pesquisa em Neurocie ˆncia Aplicada (NAPNA), Universidade de Sa ˜o Paulo (USP), Sa ˜o Paulo, Brazil R. D. Prediger Departamento de Farmacologia, Centro de Cie ˆncias Biolo ´gicas, Universidade Federal de Santa Catarina (UFSC), Campus Trindade, Floriano ´polis, SC, Brazil R. Raisman-Vozari Faculte ´ de Me ´decine, Universite ´ Pierre-et-Marie-Curie, Paris, France R. Raisman-Vozari CNRS, UMR, 7225 Paris, France R. Raisman-Vozari (&) Ho ˆpital de la Salpe ˆtrie `re/Institut du cerveau et de la moelle e ´pinie `re, 47 boulevard de l’Ho ˆpital, 75651 Paris, Cedex 13, France e-mail: ritaraisman@gmail.com 123 Neurotox Res DOI 10.1007/s12640-013-9401-8