Aggregation of alpha-synuclein to form insoluble fibrils is associated with brain disorders such as Parkinson’s disease. In this study, the authors overexpressed human wild-type alpha-synuclein in nigral dopamine neurons of rats. They found that impairments in dopamine release developed in parallel with degenerative changes in nigrostriatal terminals and axons. The earliest changes included a 50% reduction in dopamine reuptake before signs of axonal damage were observed. This was followed by reductions in dopamine release. After 2-4 months, the overall striatal innervation density was reduced by 60-80% and alpha-synuclein aggregation was seen as well as axonal damage. The authors suggest that overexpression of human alpha-synuclein first induces changes in dopamine reuptake and release, which is then followed by neuronal degeneration and cell loss.
Lundblad M, Decressac M, Mattsson B, Björklund A: Impaired neurotransmission caused by overexpression of α-synuclein in nigral dopamine neurons. Proc. Natl. Acad. Sci. USA [Epub ahead of print, Feb. 6, 2012] doi: 10.1073/pnas.1200575109