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Selective alterations of gene expression in mice induced by MPTP.
Synapse. 2005 Jan; 55(1):45-51.S

Abstract

1-methyl-4-phenyl-1,2,4,6,-tetrahydropyridine (MPTP) is a selective neurotoxin that produces striatal dopamine depletion resulting in parkinsonism like symptoms in humans and is, therefore, used to generate animal models for Parkinson's disease (PD). In this study, C57BL/6N mice were treated with MPTP acutely (3x20 mg/kg, 2-hour interval, one day injection). Mice were then sacrificed 24 hours after the last injection and brain tissue was collected for analysis. Significant decrease of striatal dopamine (DA) and the metabolites (DOPAC, HVA) was observed after MPTP treatment. MPTP also reduced protein expression of tyrosine hydroxylase (TH) in the striatum. Real time RT-PCR was used to examine selective genes of the dopaminergic system in the substantia nigra. Our data demonstrated that MPTP significantly decreased gene expression of TH, dopamine transporter (DAT), and vesicle monoamine transporter (VMAT), coinciding with the pattern of dopamine concentration changes and protein expression after MPTP treatment. Although a significant decrease of DA metabolites was observed in striatum, there was no change in the expression of monoamine oxidases (MAO-A, MAO-B) or catechol O-methyltransferase (COMT), indicating that these changes might be simply a consequence of reduced monoamine levels. In addition, gene expression of alpha-synuclein was also decreased with MPTP treatment, but there was no change in beta-synuclein and parkin. This is the first study using real-time PCR to indicate that MPTP selectively alters gene expression and provides information for clinical studies in PD. Future studies will focus on gene expression of other pathways that may be affected by MPTP treatment and investigation of gene expression in specific cell types in vivo using LCM technology.

Authors+Show Affiliations

Xu Z
Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079, USA.
Cawthon D
No affiliation info available
McCastlain KA
No affiliation info available
Slikker W
No affiliation info available
Ali SF
No affiliation info available

MeSH

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine3,4-Dihydroxyphenylacetic AcidAnimalsBrain ChemistryCorpus StriatumDopamineDopamine AgentsDopamine Plasma Membrane Transport ProteinsGene ExpressionGene Expression RegulationHomovanillic AcidMaleMembrane GlycoproteinsMembrane Transport ProteinsMiceMice, Inbred C57BLNerve Tissue ProteinsRNA, MessengerReverse Transcriptase Polymerase Chain ReactionSynucleinsTyrosine 3-MonooxygenaseVesicular Biogenic Amine Transport Proteinsalpha-Synucleinbeta-Synuclein

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15499605

Citation

Xu, Z, et al. "Selective Alterations of Gene Expression in Mice Induced By MPTP." Synapse (New York, N.Y.), vol. 55, no. 1, 2005, pp. 45-51.
Xu Z, Cawthon D, McCastlain KA, et al. Selective alterations of gene expression in mice induced by MPTP. Synapse. 2005;55(1):45-51.
Xu, Z., Cawthon, D., McCastlain, K. A., Slikker, W., & Ali, S. F. (2005). Selective alterations of gene expression in mice induced by MPTP. Synapse (New York, N.Y.), 55(1), 45-51.
Xu Z, et al. Selective Alterations of Gene Expression in Mice Induced By MPTP. Synapse. 2005;55(1):45-51. PubMed PMID: 15499605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective alterations of gene expression in mice induced by MPTP. AU - Xu,Z, AU - Cawthon,D, AU - McCastlain,K A, AU - Slikker,W,Jr AU - Ali,S F, PY - 2004/10/23/pubmed PY - 2005/2/18/medline PY - 2004/10/23/entrez SP - 45 EP - 51 JF - Synapse (New York, N.Y.) JO - Synapse VL - 55 IS - 1 N2 - 1-methyl-4-phenyl-1,2,4,6,-tetrahydropyridine (MPTP) is a selective neurotoxin that produces striatal dopamine depletion resulting in parkinsonism like symptoms in humans and is, therefore, used to generate animal models for Parkinson's disease (PD). In this study, C57BL/6N mice were treated with MPTP acutely (3x20 mg/kg, 2-hour interval, one day injection). Mice were then sacrificed 24 hours after the last injection and brain tissue was collected for analysis. Significant decrease of striatal dopamine (DA) and the metabolites (DOPAC, HVA) was observed after MPTP treatment. MPTP also reduced protein expression of tyrosine hydroxylase (TH) in the striatum. Real time RT-PCR was used to examine selective genes of the dopaminergic system in the substantia nigra. Our data demonstrated that MPTP significantly decreased gene expression of TH, dopamine transporter (DAT), and vesicle monoamine transporter (VMAT), coinciding with the pattern of dopamine concentration changes and protein expression after MPTP treatment. Although a significant decrease of DA metabolites was observed in striatum, there was no change in the expression of monoamine oxidases (MAO-A, MAO-B) or catechol O-methyltransferase (COMT), indicating that these changes might be simply a consequence of reduced monoamine levels. In addition, gene expression of alpha-synuclein was also decreased with MPTP treatment, but there was no change in beta-synuclein and parkin. This is the first study using real-time PCR to indicate that MPTP selectively alters gene expression and provides information for clinical studies in PD. Future studies will focus on gene expression of other pathways that may be affected by MPTP treatment and investigation of gene expression in specific cell types in vivo using LCM technology. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/15499605/Selective_alterations_of_gene_expression_in_mice_induced_by_MPTP_ DB - PRIME DP - Unbound Medicine ER -