Bimolecular Fluorescence Complementation of Alpha-synuclein Demonstrates its Oligomerization with Dopaminergic Phenotype in Mice

Alpha-synuclein (alpha Syn) is encoded by the first causal gene identified in Parkinson's disease (PD) and is the main component of Lewy bodies, a pathological hallmark of PD. aSyn-based animalmodels have contributed to our understanding of PD pathophysiology and to the development of therapeutics. Overexpression of human wildtype alpha Syn by viral vectors in rodents recapitulates the loss of dopaminergic neurons fromthe substantia nigra, another defining pathological feature of the disease. The development of a rat model exhibiting bimolecular fluorescence complementation (BiFC) of alpha Syn by recombinant adeno-associated virus facilitates detection of the toxic alpha Syn oligomers species. We report here neurochemical, neuropathological and behavioral characterization of BiFC of alpha Syn in mice. Overexpression and oligomerization of alpha Syn through BiFC is detected by conjugated fluorescence. Reduced striatal dopamine and loss of nigral dopaminergic neurons are accompanied neuroinflammation and abnormalmotor activities. Our mousemodel may provide a valuable tool to study the role of alpha Syn in PD and to explore therapeutic approaches. (C) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.