• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

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 ID: 12009758

Authors

  • Richfield EK
  • Thiruchelvam MJ
  • Cory-Slechta DA
  • Wuertzer C
  • Gainetdinov RR
  • Caron MG
  • Di Monte DA
  • Federoff HJ

Journal

Experimental neurology

Publication Data

May 15, 2002

Associated Grants

  • Agency: NIEHS NIH HHS, Id: ES01247
  • Agency: NIEHS NIH HHS, Id: ES05017
  • Agency: NIEHS NIH HHS, Id: ES05905
  • Agency: NINDS NIH HHS, Id: NS 19576
  • Agency: NINDS NIH HHS, Id: NS36420
  • Agency: NIEHS NIH HHS, Id: R01 ES09391

Mesh Terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Aging
  • Amphetamine
  • Animals
  • Behavior, Animal
  • Brain
  • Corpus Striatum
  • Disease Models, Animal
  • Disease Progression
  • Dopamine
  • Dopamine Plasma Membrane Transport Proteins
  • Genetic Predisposition to Disease
  • Humans
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Mice
  • Mice, Transgenic
  • Motor Activity
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins
  • Parkinson Disease
  • Parkinson Disease, Secondary
  • Presynaptic Terminals
  • Promoter Regions, Genetic
  • Substantia Nigra
  • Synucleins
  • Tyrosine 3-Monooxygenase
  • alpha-Synuclein