Fig. 2

Effects of Lrrk2 ablation in α-synuclein spreading in rats. Spreading of α-synuclein is decreased in LRRK2-deficient rats. Wild-type (WT) and LRRK2-deficient (KO) rats received a single injection of AAVs encoding human α-synuclein (hα-syn) into the left vagus nerve. Spreading of α-synuclein was analyzed 8 and 12 weeks later. a Representative images of axons stained with an antibody against human α-synuclein in the left (AAV-injected side) pons of a WT and a KO rat killed at 12 weeks post-AAV injection. Scale bar: 5 μm. b The number of axons immunoreactive for human α-synuclein was quantified in the left pons (Bregma: −9.48 mm) of WT (N = 4/time point) and KO (N = 4/time point) rats. Error bars represent SEM. c, d Length (c) and density (d) of axons immunoreactive for human α-synuclein were estimated in the left pons in an area encompassing the coeruleus/subcoeruleus complex and the parabrachial nucleus. Samples were obtained from rats killed at 8 (N = 4 WT and N = 4 KO) and 12 (N = 4 WT and N = 4 KO) weeks post-AAV injection and, for each animal, measurements were carried out on three separate pontine sections. Data at the two time points were pooled and analyzed together. Error bars represent SEM, * p < 0.05 by unpaired, two-tailed Student’s t test. e The number of axons positive for human α-synuclein was quantified in the left caudal midbrain (cMB; Bregma: −7.8 mm), rostral midbrain (rMB; Bregma: −6.0 mm) and forebrain (FB; Bregma: −2.4 mm) of WT (N = 4 at 8 weeks and N = 4 at 12 weeks) and KO (N = 4 at 8 weeks and N = 4 at 12 weeks) rats. Error bars represent SEM, * p < 0.05 by unpaired, two-tailed Student’s t test