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

Author(s)

Tristao, Fabrine S. M. ^[1] ; Amar, Majid ^[1] ; Latrous, Ines ^[1] ; Del-Bel, Elaine A. ^{[2, 3]} ; Prediger, Rui D. ^[4] ; Raisman-Vozari, Rita ^{[1, 5, 6, 7]}

Affiliation

^[1] CRICM, UMR 975, INSERM, Paris - France

^[2] Univ Sao Paulo, Dept MEF Fisiol, Fac Odontol Ribeirao Preto, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, NAPNA, BR-09500900 Sao Paulo - Brazil

^[4] Univ Fed Santa Catarina, Dept Farmacol, Ctr Ciencias Biol, Florianopolis, SC - Brazil

^[5] Univ Paris 06, Fac Med, Paris - France

^[6] CNRS, UMR, F-7225 Paris - France

^[7] Hop La Pitie Salpetriere, Inst Cerveau & Moelle Epiniere, F-75651 Paris 13 - France

• Document type: Journal article
• Source: NEUROTOXICITY RESEARCH; v. 25, n. 1, p. 24-32, JAN 2014.
• Web of Science Citations: 13

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 (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. (AU)

• FAPESP's process: 08/55092-9 - Analysis of nitric oxide synthase in dopaminergic and non dopaminergic neurons in experimental Parkinson Disease: role of NOS inhibitors in L-DOPA induced diskinesias
• Grantee: Elaine Aparecida Del Bel Belluz Guimarães
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants