FN075 did not enhance pathological α-synuclein expression in the AAV-α-synuclein model
Having established that AAV-α-synuclein led to human α-synuclein overexpression in the nigrostriatal pathway, we explored what forms the protein took, and whether or not pathological forms were exacerbated by FN075 administration. Thus, we performed further immunohistochemical staining specific for pS129-α-synuclein. Immunostaining revealed a significant increase in the number of nigral cell bodies in which pathological pS129-α-synuclein had accumulated in the groups which received AAV-α-synuclein (Fig. 3a; Group, F (3,36)=15.10, p < 0.05). However, there was no build-up of cellular pS129-α-synuclein in the substantia nigra as a result of FN075, either alone or in combination with AAV-α-synuclein. Similarly when assessing the number of pS129-α-synuclein aggregations found in the striatum on the side of the injection, there was a significant increase in the groups receiving the AAV-α-synuclein vector (Fig. 3b; Group,F (3,35) =10.75, p < 0.05), yet FN075 did not have any additive effect on the amount of staining. Finally, we carried out an immunohistochemical stain for aggregate specific α-synuclein which showed a significant increase in fibrillar α-synuclein in the substantia nigra in both groups receiving AAV-α-synuclein (Fig. 4; Group, F (3,35) =7.56, p < 0.05). However, again there was no added pathology induced by the sequential exposure to FN075.