Fig. 4
Post mortem evaluation of cardiac sympathetic innervation. a–c Photomicrographs of cardiac left ventricle sections immunostained with the sympathetic innervation marker tyrosine hydroxylase (TH) and counterstained with hematoxylin. a Corresponds to controls, b placebo-, and (c) pioglitazone-treated monkeys. TH-immunoreactivity (−ir) was observed in bundles of nerves (white+), typically adjacent to blood vessels, and in individual nerve fibers, as previously described (Joers et al., 2014). Qualitatively, TH-ir was robustly present in nerve bundles and fibers of healthy controls and diminished in 6-OHDA-treated subjects. d Plot of repeated measures correlation of cardiac nerve bundle TH-ir percent area above threshold (%AAT) with 12-week MHED uptake in placebo- and pioglitazone-treated animals. Each point represents a single anatomical area in one animal (12 total anatomical areas (4 regions × 3 levels) per animal; 10 animals). A significant repeated measures correlation was found between TH-ir and 12-week MHED uptake in all ten animals (rrm = 0.44, p < 0.000002). This correlation was also significant when treatment groups were analyzed separately and was similar between groups (placebo: rrm = 0.47, p < 0.0004; pioglitazone: rrm = 0.41, p < 0.002). 12-week MHED PET data included in the repeated measures correlation were matched to levels and regions analyzed by post mortem immunohistochemistry (MHED PET levels 1, 4 and 6; MHED PET regions SA, AL, LI and IS). Scale bar = 50 μm.
