Streptozotocin (STZ) administered to mice intracerebrally depletes brain insulin levels and induces progressive neurodegeneration that corresponds to the clinical symptoms of AD. Impairments in insulin and insulin-like growth factor signaling are observed in AD brains and these abnormalities increase concomitantly with dementia [57, 58]. Treatment with the PPARδ agonist, L-160,043, prevented STZ-induced neurodegeneration and ameliorated cognitive impairment as evaluated by the Morris Water Maze task. These effects of L-160,043 were attributed to (i) increased insulin receptor signaling, (ii) reduced tau phosphorylation, (iii) increased choline acetyltransferase, and (iv) attenuated inflammation and oxidative stress. Consistent with the effects of GW0742 described above, L-160,043 reduced levels of GFAP. Furthermore, L-160,043 reduced immunoreactivity of the oxidative stress markers, 8-hydroxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE), relative to STZ-treated animals [15]. Elevated levels of 8-OHdG and HNE have been detected in AD brains [59, 60]. This suggests that PPARδ agonists may be efficacious antioxidant agents to ameliorate oxidative stress associated with AD. Interestingly, the actions of L-160,043 were more pronounced than the PPARα agonist, GW7647, or partial PPARγ agonist, F-L-Leu [15]. It is important to note that
