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Res of AD cerebellar atrophy include, reductions in Purkinje cell population, atrophy of the molecular and granule cell layers [68], increased amyloid deposition and gliosis in the cortex [69]; increased ubiquitin-immunoreactivity in senile plaques and degenerating neurites [70]; extensive abnormalities in dendritic spine density and synaptic structure in vestibulocerebellar, visual, and auditory
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Www.biomedcentral.com/1472-6823/10/Page 6 ofthe context of peripheral insulin resistance or T2DM. Similar results have been reported previously, in which the investigators generated models with much higher doses of NDEA [84]. One potential explanation for this paradox is that homeostatic mechanisms may have shifted toward increased storage of lipids/triglycerides in adipose tissue, skeletal muscle
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Y effects of NDEA on insulin receptor, IGF2 receptor, and IRS-2 were muted by the chronic HFD feeding. Moreover, the main effect of NDEA, irrespective of HFD feeding, was to reduce tau gene expression, whereas chronic HFD feeding, irrespective of NDEA treatment, significantly inhibited ChAT. The only unique effect of HFD+NDEA treatment was to reduce insulin gene expression in the brain.Effects of
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S described elsewhere [79]. For molecular and biochemical assays, cerebella were snap-frozen in a dry ice-methanol bath and stored at -80 . We studied cerebellar tissue because the cerebellum: 1) requires intact insulin/IGF signaling to maintain its structural and functional integrity [80,81]; 2) is severely damaged by i.c.-STZ mediated neurodegeneration [19,22]; 3) although relatively spared, it