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

Author(s):Show less -

Prediger, Rui D. S. ^[1] ; Aguiar, Jr., Aderbal S. ^[1] ; Rojas-Mayorquin, Argelia Esperanza ^{[2, 3, 4]} ; Figueiredo, Claudia P. ^[1] ; Matheus, Filipe C. ^[1] ; Ginestet, Laure ^{[2, 3, 4]} ; Chevarin, Caroline ^[5] ; Del Bel, Elaine ^[6] ; Mongeau, Raymond ^[5] ; Hamon, Michel ^[5] ; Lanfumey, Laurence ^[5] ; Raisman-Vozari, Rita ^{[2, 3, 4]}

Affiliation

^[1] Univ Fed Santa Catarina, Ctr Ciencias Biol, Dept Farmacol, BR-88049900 Florianopolis, SC - Brazil

^[2] CNRS, UMR 7225, Paris - France

^[3] Univ Paris 06, Ctr Rech Inst Cerveau & Moelle Epiniere, UMR S975, Paris - France

^[4] INSERM, U975, Paris - France

^[5] Univ Paris 06, INSERM, UMR 677, F-75013 Paris - France

^[6] Univ Sao Paulo, Fac Odontol Ribeirao Preto, Dept MEF Fisiol, BR-14049 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: NEUROTOXICITY RESEARCH; v. 17, n. 2, p. 114-129, FEB 2010.
• Web of Science Citations: 67

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. (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