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Ative stress with lipid peroxidation, as occur in AD. The finding that chronic HFD feeding did not significantly alter tau or AbPP expression also supports our previous conclusion that HFD feeding contributes to, but is not sufficient to cause AD-type neurodegeneration [45,46]. The combined effect of early, limited NDEA exposure plus chronic HFD feeding significantly reduced insulin and ChAT mRNA
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Ld lower than the cumulative doses needed to produce cancer in experimental animals [93-96], and beginning in early adolescence, we pair-fed the rats with either high (60 ) or low (5 ) fat containing diets. The NDEA doses were selected to be far below those needed for carcinogenesis and were based on empirical studies demonstrating absence of acute toxic effects in the rats.Longer durations of NDE
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Affected in AD, as well as other neurodegenerative diseases [47,50, 53,56,59,60,65,68,69,71], and cerebellar degeneration causes cognitive impairment [49,57-59,62,63,66,67,72]. Previous studies demonstrated significant structural, functional, and metabolic abnormalities in AD cerebella [57-59,82], including insulin and IGF resistance [30],similar to the findings in more traditional targets of AD,
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Ration have soared over the past several decades, suggesting that exposures rather than genetics dictate their etiologies. Our over-arching hypothesis is that shifts in lifestyles and economics have led us to chronically consume excess fat, and get exposed to agents that cause insulin resistance. Consideration given to potential pathogenic agents was focused by the experimental evidence showing th
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P. Chronic HFD feeding aloneTable 3 Effects of High Fat Diet and NDEA Exposure on Biomarkers of Insulin and IGF Resistance in the CerebellummRNA AbPP Tau AChE ChAT Insulin IGF-1 IGF-2 Insulin R IGF-1R IGF-2R IRS-1 IRS-2 IRS-4 LFD+VEH 7.007 ?0.828 12.230 ?1.098 2.829 ?0.178 0.701 ?0.045 0.754 ?0.048 0.957 ?0.119 12.000 ?1.800 17.090 ?1.547 5.031 ?0.525 5.677 ?0.548 5.559 ?0.411 7.701 ?0.509 0.135 ?
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S, could result in cytoskeletal collapse and synaptic disconnection. Alternatively, the finding could reflect neuronal loss associated with neurodegeneration. The reduced levels of ChAT reflect deficits in acetylcholine homeostasis that contribute to cognitive impairment with neurodegeneration [101,102]. Correspondingly, in preliminary studies, we detected evidence of significant spatial learning
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S, could result in cytoskeletal collapse and synaptic disconnection. Alternatively, the finding could reflect neuronal loss associated with neurodegeneration. The reduced levels of ChAT reflect deficits in acetylcholine homeostasis that contribute to cognitive impairment with neurodegeneration [101,102]. Correspondingly, in preliminary studies, we detected evidence of significant spatial learning
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S, could result in cytoskeletal collapse and synaptic disconnection. Alternatively, the finding could reflect neuronal loss associated with neurodegeneration. The reduced levels of ChAT reflect deficits in acetylcholine homeostasis that contribute to cognitive impairment with neurodegeneration [101,102]. Correspondingly, in preliminary studies, we detected evidence of significant spatial learning