Early synaptic dysfunction induced by α-synuclein in a rat model of Parkinson's disease.

ABSTRACT: Evidence suggests that synapses are affected first in Parkinson's disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats that overexpress human α-synuclein by local injection of viral-vectors in midbrain. We aimed to achieve α-synuclein levels sufficient to induce terminal pathology without significant loss of nigral neurons. We tested synaptic disruption in vivo by analyzing motor defects and binding of a positron emission tomography (PET) radioligand to the vesicular monoamine transporter 2, (VMAT2), [¹¹C]dihydrotetrabenazine (DTBZ). Animals overexpressing α-synuclein had progressive motor impairment and, 12 weeks

SUBMITTER: Phan JA 

PROVIDER: S-EPMC5526979 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature