Fig. 5.

Pharmacological kinase inhibition (PF-360) protects against dopaminergic neurodegeneration induced by human G2019S LRRK2. (A) Ad5-G2019S-LRRK2 vectors were unilaterally delivered at six distinct locations (1.5 × 10¹⁰ vp/site, in 2.5 μL) to the rat striatum. Rats were fed continuously with control (vehicle) or PF-360 (175 mg/kg) chow from days 7 to 42 postinjection. Brain tissues were harvested at 42 d postinjection and subjected to immunohistochemical analysis. (B) Immunohistochemistry reveals expression of human LRRK2 (anti-FLAG antibody) in striatum and nigra, or nigral dopaminergic neurons (anti-TH antibody), of rats at 42 d postinjection. Images indicate low and high magnification for each group and brain region. TH sections were counterstained with Cresyl violet. (Scale bars: 500 μm.) (C) Unbiased stereological analysis of TH-positive dopaminergic and total Nissl-positive neuron number in the substantia nigra at 42 d postinjection. Bars represent % neuronal loss in the injected ipsilateral nigra relative to the contralateral nigra (mean ± SEM, n = 12 animals/group), *P < 0.05 by unpaired Student’s t test; n.s., nonsignificant. (D) Immunohistochemistry at 42 d postinjection showing expression of Ad5 capsid (anti-hexon) in the ipsilateral striatum, or microglia (Iba1) and astrocytes (GFAP) in striatum and substantia nigra of rats expressing human G2019S-LRRK2 treated with vehicle or PF-360 chow. (Scale bars: 500 μm.)