Direct detection of alpha synuclein oligomers in vivo

Hemi Dimant, Suneil K Kalia, Lorraine V Kalia, Liya N Zhu, Laura Kibuuka, Darius Ebrahimi-Fakhari, Nikolaus R McFarland, Zhanyun Fan, Bradley T Hyman, Pamela J McLean

Rat models of Parkinson's disease are widely used to elucidate the mechanisms underlying disease etiology or to investigate therapeutic approaches. Models were developed using toxins such as MPTP or 6-OHDA to specifically target dopaminergic neurons resulting in acute neuronal loss in the substantia nigra or by using viral vectors to induce the specific and gradual expression of alpha synuclein in the substantia nigra. The detection of alpha- synuclein oligomers, the presumed toxic species, in these models and others has been possible using only indirect biochemical approaches to date. Here we coinjected AAVs encoding alpha-synuclein fused to the N- or C-terminal half of VenusYFP in rat substantia nigra pars compacta and describe for the first time a novel viral vector rodent model with the unique ability to directly detect and track alpha synuclein oligomers ex vivo and in vivo.