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Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice.
Exp Neurol. 2002 May; 175(1):35-48.EN

Abstract

Human alpha-synuclein (halpha-SYN) is implicated in the Parkinson's disease phenotype (PDP) based on a variety of studies in man, animal models, and in vitro studies. The normal function of halpha-SYN and the mechanism by which it contributes to the PDP remains unclear. We created transgenic mice expressing either wild-type (hwalpha-SYN) or a doubly mutated (hm2alpha-SYN) form of halpha-SYN under control of the 9-kb rat tyrosine hydroxylase promoter. These mice expressed halpha-SYN in cell bodies, axons, and terminals of the nigrostriatal system. The expression of halpha-SYN in nigrostriatal terminals produced effects in both constructs resulting in increased density of the dopamine transporter and enhanced toxicity to the neurotoxin MPTP. Expression of hm2alpha-SYN reduced locomotor responses to repeated doses of amphetamine and blocked the development of sensitization. Adult hwalpha-SYN-5 transgenic mice had unremarkable dopaminergic axons and terminals, normal age-related measures on two motor coordination screens, and normal age-related measures of dopamine (DA) and its metabolites. Adult hm2alpha-SYN-39 transgenic mice had abnormal axons and terminals, age-related impairments in motor coordination, and age-related reductions in DA and its metabolites. Expression of hm2alpha-SYN adversely affects the integrity of dopaminergic terminals and leads to age-related declines in motor coordination and dopaminergic markers.

Authors+Show Affiliations

Department of Pathology and Lab Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, New York 14642, USA.No 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
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12009758

Citation

Richfield, Eric K., et al. "Behavioral and Neurochemical Effects of Wild-type and Mutated Human Alpha-synuclein in Transgenic Mice." Experimental Neurology, vol. 175, no. 1, 2002, pp. 35-48.
Richfield EK, Thiruchelvam MJ, Cory-Slechta DA, et al. Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice. Exp Neurol. 2002;175(1):35-48.
Richfield, E. K., Thiruchelvam, M. J., Cory-Slechta, D. A., Wuertzer, C., Gainetdinov, R. R., Caron, M. G., Di Monte, D. A., & Federoff, H. J. (2002). Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice. Experimental Neurology, 175(1), 35-48.
Richfield EK, et al. Behavioral and Neurochemical Effects of Wild-type and Mutated Human Alpha-synuclein in Transgenic Mice. Exp Neurol. 2002;175(1):35-48. PubMed PMID: 12009758.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice. AU - Richfield,Eric K, AU - Thiruchelvam,Mona J, AU - Cory-Slechta,Deborah A, AU - Wuertzer,Charles, AU - Gainetdinov,Raul R, AU - Caron,Marc G, AU - Di Monte,Donato A, AU - Federoff,Howard J, PY - 2002/5/16/pubmed PY - 2002/5/25/medline PY - 2002/5/16/entrez SP - 35 EP - 48 JF - Experimental neurology JO - Exp Neurol VL - 175 IS - 1 N2 - Human alpha-synuclein (halpha-SYN) is implicated in the Parkinson's disease phenotype (PDP) based on a variety of studies in man, animal models, and in vitro studies. The normal function of halpha-SYN and the mechanism by which it contributes to the PDP remains unclear. We created transgenic mice expressing either wild-type (hwalpha-SYN) or a doubly mutated (hm2alpha-SYN) form of halpha-SYN under control of the 9-kb rat tyrosine hydroxylase promoter. These mice expressed halpha-SYN in cell bodies, axons, and terminals of the nigrostriatal system. The expression of halpha-SYN in nigrostriatal terminals produced effects in both constructs resulting in increased density of the dopamine transporter and enhanced toxicity to the neurotoxin MPTP. Expression of hm2alpha-SYN reduced locomotor responses to repeated doses of amphetamine and blocked the development of sensitization. Adult hwalpha-SYN-5 transgenic mice had unremarkable dopaminergic axons and terminals, normal age-related measures on two motor coordination screens, and normal age-related measures of dopamine (DA) and its metabolites. Adult hm2alpha-SYN-39 transgenic mice had abnormal axons and terminals, age-related impairments in motor coordination, and age-related reductions in DA and its metabolites. Expression of hm2alpha-SYN adversely affects the integrity of dopaminergic terminals and leads to age-related declines in motor coordination and dopaminergic markers. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/12009758/Behavioral_and_neurochemical_effects_of_wild_type_and_mutated_human_alpha_synuclein_in_transgenic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014488602978829 DB - PRIME DP - Unbound Medicine ER -