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.