FIGURE 5.

Microgliosis associated with G2019S-LRRK2 expression is attenuated by PF-06447475 in G2019S-LRRK2 rats. 10- to 12-week-old male G2019S-LRRK2 BAC transgenic rats and G2019S− controls were unilaterally injected with 6 × 10⁹ rAAV2 α-synuclein viral particles and treated with 30 mg·kg⁻¹ b.i.d. by oral gavage with either PF-06447475 (PF-475) or control compound for 4 weeks. Four rats were analyzed per experimental group by confocal analysis of serial sections across the ipsilateral SNpc for each animal. A and B, representative confocal sections of the ipsilateral SNpc from G2019S+ rats (A) or G2019S− rats triple-stained for Iba1, MHC-II, and iNOS (B) in grayscale (to enhance contrast) together with colored merged images (blue, Iba1; green, MHC-II; magenta, iNOS). iNOS-positive cells were not identified in most sections of the SNpc, with the exception of G2019S+ control compound-treated rats. MCH-II- or iNOS-positive cells could not be found in the contralateral side in any group. C, fractional area of immunoreactivity for Iba1 calculated from equivalent fields across the SNpc of control or PF-06447475-treated G2019S+ and G2019S− rats. Scale bars = 10 μm. *, p < 0.05; **, p < 0.01; n.s., p > 0.05, as calculated with one-way analysis of variance with Tukey's post hoc comparison. Data are mean ± S.E.