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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.
Neurotox Res. 2010 Feb; 17(2):114-29.NR

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.

Authors+Show Affiliations

Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil. ruidsp@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19629612

Citation

Prediger, Rui D S., et al. "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." Neurotoxicity Research, vol. 17, no. 2, 2010, pp. 114-29.
Prediger RD, Aguiar AS, Rojas-Mayorquin AE, et al. 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. Neurotox Res. 2010;17(2):114-29.
Prediger, R. D., Aguiar, A. S., Rojas-Mayorquin, A. E., Figueiredo, C. P., Matheus, F. C., Ginestet, L., Chevarin, C., Bel, E. D., Mongeau, R., Hamon, M., Lanfumey, L., & Raisman-Vozari, R. (2010). 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. Neurotoxicity Research, 17(2), 114-29. https://doi.org/10.1007/s12640-009-9087-0
Prediger RD, et al. 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. Neurotox Res. 2010;17(2):114-29. PubMed PMID: 19629612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Prediger,Rui D S, AU - Aguiar,Aderbal S,Jr AU - Rojas-Mayorquin,Argelia Esperanza, AU - Figueiredo,Claudia P, AU - Matheus,Filipe C, AU - Ginestet,Laure, AU - Chevarin,Caroline, AU - Bel,Elaine Del, AU - Mongeau,Raymond, AU - Hamon,Michel, AU - Lanfumey,Laurence, AU - Raisman-Vozari,Rita, Y1 - 2009/07/21/ PY - 2009/04/14/received PY - 2009/07/02/accepted PY - 2009/06/29/revised PY - 2009/7/25/entrez PY - 2009/7/25/pubmed PY - 2010/3/3/medline SP - 114 EP - 29 JF - Neurotoxicity research JO - Neurotox Res VL - 17 IS - 2 N2 - 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. SN - 1476-3524 UR - https://www.unboundmedicine.com/medline/citation/19629612/Single_intranasal_administration_of_1_methyl_4_phenyl_1236_tetrahydropyridine_in_C57BL/6_mice_models_early_preclinical_phase_of_Parkinson's_disease_ L2 - https://dx.doi.org/10.1007/s12640-009-9087-0 DB - PRIME DP - Unbound Medicine ER -