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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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S such as diabetes mellitus [74], chronicTong et al. BMC Endocrine Disorders 2010, 10:4 http://www.biomedcentral.com/1472-6823/10/Page 3 ofalcoholism [75], or obesity with metabolic syndrome [45,46]. These systemic diseases share in common with primary central nervous system (CNS) degenerative diseases, impairments in cognition, and deficits in insulin and IGF signaling mechanisms, insulin/IGF res
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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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N.edu 1 Department of Pathology (Neuropathology), Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USAnoted that the striking increases in AD and PD mortality rates followed sharply increased consumption of processed foods, use of preservatives, and demand for nitrogen-containing fertilizers [4]. A common theme resonating from these unnecessary lifestyle trends is that we have inadver
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Urces. Therefore, we entertained the hypothesis that either limited or chronic low-level exposures to nitrosamines account for the observed shifts in morbidity and mortality from insulin resistance diseases. Moreover, given the clear role of high dietary fat intake as a mediator of obesity, T2DM, or cognitive impairment, we proposed that the combined effects of HFD and NDEA exposure may act additi
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In brain [85-88]; 2) cause cytotoxicity and insulin resistance [83,88]; and 3) are increased in brains with neurodegeneration [85,89-91]. We measured mRNA levels of ceramide synthases (CER), UDP glucose ceramide glycosyltransferase (UGCG), serine palmitoyltransferase (SPTLC), and sphingomyelin phosphodiesterases (SMPD), due to their demonstrated relevance to neurodegeneration [45,83]. HFD feeding
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D (Ex 579 nm/Em 595 nm) in a Spectromax M5, and results were normalized to sample protein content in the wells. Box plots depict mean, range ?S.D. of results (N = 8-10/group). Inter-group comparisons were made using ANOVA with the post-hoc Bonferroni multiple comparisons test of significance. Significant P-values are indicated within the panels.Tong et al. BMC Endocrine Disorders 2010, 10:4 http:/
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Antibody (1:10000) and Amplex Red soluble fluorophore [79]. Amplex Red fluorescence was measured (Ex 579/Em 595) in a SpectraMax M5 microplate reader (Molecular Devices Corp., Sunnyvale, CA). Negative control reactions included substitutions with nonrelevant primary or secondary antibodies, and omission of primary or secondary antibody. Immunoreactivities were normalized to protein content as dete