Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2002 May;175(1):35-48.
doi: 10.1006/exnr.2002.7882.

Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice

Eric K Richfield  1 , Mona J Thiruchelvam, Deborah A Cory-Slechta, Charles Wuertzer, Raul R Gainetdinov, Marc G Caron, Donato A Di Monte, Howard J Federoff
Affiliations

Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice

Eric K Richfield et al. Exp Neurol. 2002 May.

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.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources