A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice.

ABSTRACT:

Background

Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons.

Methodology/principal findings

Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also m

SUBMITTER: Kurz A 

PROVIDER: S-EPMC2898885 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature