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MPTP-induced model of Parkinson's disease in cytochrome P450 2E1 knockout mice.
Neuropharmacology. 2009 Jun; 56(8):1075-81.N

Abstract

Evidence for involvement of cytochrome P450 2E1 in the MPTP-induced mouse model of PD has been reported [Vaglini, F., Pardini, C., Viaggi, C., Bartoli, C., Dinucci, D., Corsini, G.U., 2004. Involvement of cytochrome P450 2E1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease. J. Neurochem. 91, 285-298]. We studied the sensitivity of Cyp2e1(-/-) mice to the acute administration of MPTP in comparison with their wild-type counterparts. In Cyp2e1(-/-) mice, the reduction of striatal DA content was less pronounced 7 days after MPTP treatment compared to treated wild-type mice. Similarly, TH immunoreactivity analysis of the substantia nigra of Cyp2e1(-/-) mice did not show any neuronal lesions after MPTP treatment. In contrast to this, wild-type animals showed a minimal but significant lesioning by the toxin as evaluated also by means of non-stereologic computerized assisted analysis of this brain area. Striatal levels of DA metabolites after 7 days were variably affected by the toxin, but consistent differences between the two animal strains were not observed. We evaluated short-term changes in the levels of striatal DA and its metabolites, and we monitored striatal MPP(+) levels. Striatal MPP(+) was cleared more rapidly in Cyp2e1(-/-) mice than in wild-type animals and, consistently, striatal DA content decreased faster in Cyp2e1(-/-) mice than in wild-type animals, and 3-methoxytyramine and HVA levels showed an early and sharp rise. Our findings suggest that Cyp2e1(-/-) mice are weakly sensitive to MPTP-induced brain lesions, markedly in contrast with a protective role of the enzyme as suggested previously. The differences observed between the knockout mice and their wild-type counterparts are modest and may be due to an efficient compensatory mechanism or genetic drift in the colonies.

Authors+Show Affiliations

Department of Neuroscience, Section of Pharmacology, University of Pisa and Center of Excellence AMBISEN for the Study of Environmental Toxins and CNS Diseases, Pisa, Italy. f.vaglini@drugs.med.unipi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19298832

Citation

Viaggi, C, et al. "MPTP-induced Model of Parkinson's Disease in Cytochrome P450 2E1 Knockout Mice." Neuropharmacology, vol. 56, no. 8, 2009, pp. 1075-81.
Viaggi C, Vaglini F, Pardini C, et al. MPTP-induced model of Parkinson's disease in cytochrome P450 2E1 knockout mice. Neuropharmacology. 2009;56(8):1075-81.
Viaggi, C., Vaglini, F., Pardini, C., Caramelli, A., & Corsini, G. U. (2009). MPTP-induced model of Parkinson's disease in cytochrome P450 2E1 knockout mice. Neuropharmacology, 56(8), 1075-81. https://doi.org/10.1016/j.neuropharm.2009.03.003
Viaggi C, et al. MPTP-induced Model of Parkinson's Disease in Cytochrome P450 2E1 Knockout Mice. Neuropharmacology. 2009;56(8):1075-81. PubMed PMID: 19298832.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MPTP-induced model of Parkinson's disease in cytochrome P450 2E1 knockout mice. AU - Viaggi,C, AU - Vaglini,F, AU - Pardini,C, AU - Caramelli,A, AU - Corsini,G U, Y1 - 2009/03/17/ PY - 2008/12/03/received PY - 2009/03/05/revised PY - 2009/03/10/accepted PY - 2009/3/21/entrez PY - 2009/3/21/pubmed PY - 2009/8/29/medline SP - 1075 EP - 81 JF - Neuropharmacology JO - Neuropharmacology VL - 56 IS - 8 N2 - Evidence for involvement of cytochrome P450 2E1 in the MPTP-induced mouse model of PD has been reported [Vaglini, F., Pardini, C., Viaggi, C., Bartoli, C., Dinucci, D., Corsini, G.U., 2004. Involvement of cytochrome P450 2E1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease. J. Neurochem. 91, 285-298]. We studied the sensitivity of Cyp2e1(-/-) mice to the acute administration of MPTP in comparison with their wild-type counterparts. In Cyp2e1(-/-) mice, the reduction of striatal DA content was less pronounced 7 days after MPTP treatment compared to treated wild-type mice. Similarly, TH immunoreactivity analysis of the substantia nigra of Cyp2e1(-/-) mice did not show any neuronal lesions after MPTP treatment. In contrast to this, wild-type animals showed a minimal but significant lesioning by the toxin as evaluated also by means of non-stereologic computerized assisted analysis of this brain area. Striatal levels of DA metabolites after 7 days were variably affected by the toxin, but consistent differences between the two animal strains were not observed. We evaluated short-term changes in the levels of striatal DA and its metabolites, and we monitored striatal MPP(+) levels. Striatal MPP(+) was cleared more rapidly in Cyp2e1(-/-) mice than in wild-type animals and, consistently, striatal DA content decreased faster in Cyp2e1(-/-) mice than in wild-type animals, and 3-methoxytyramine and HVA levels showed an early and sharp rise. Our findings suggest that Cyp2e1(-/-) mice are weakly sensitive to MPTP-induced brain lesions, markedly in contrast with a protective role of the enzyme as suggested previously. The differences observed between the knockout mice and their wild-type counterparts are modest and may be due to an efficient compensatory mechanism or genetic drift in the colonies. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/19298832/MPTP_induced_model_of_Parkinson's_disease_in_cytochrome_P450_2E1_knockout_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(09)00070-7 DB - PRIME DP - Unbound Medicine ER -