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In HeLa cells. Autophagy. 2011;7(1):27?9. 64. Debnath J, Mills KR, Collins NL, Reginato MJ, Muthuswamy SK, Brugge JS. The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell. 2002;111(1):29?0. 65. Fung C, Lock R, Gao S, Salas E, Debnath J. Induction of autophagy during extracellular matrix detachment promotes cell survival. Mol Biol
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Ry. Early limited exposure to NDEA had no significant effect on any of the indices measured relative to control. Chronic HFD feeding significantly increased the mean levels of pGSK-3b, GFAP, and N-Tyr relative to all other groups (P
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Software (GraphPad Software, Inc., San Diego, CA). Software generated significant P-values are shown in the graphs or included in the tables.ResultsEffects of NDEA and HFD on Serum Biomarkers of T2DM (Table 2)Tissue homogenates were prepared in radioimmunoprecipitation assay buffer containing protease and phosphatase inhibitors, as previously described [46]. Direct ELISAs were performed in 96-well
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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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Or NDEA-associated neurodegeneration and insulin/IGF resistance were likely mediated by increased brain ceramide levels. Those studies demonstrated strikingly increased expression of several genes regulating ceramide production via both de novo biosynthesis or sphingomyelin degradation pathways in NDEA-treated rats, irrespective of chronic HFD feeding. Since NDEA is lipid soluble [115,116] and can
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We measured gene expression corresponding to insulin and IGF polypeptides and receptors, and insulin receptor substrates (IRSs) that transmit signals required for growth, survival, energy metabolism, and neuronalELISAs were used to measure sustained effects of NDEA treatment and/or chronic HFD feeding on Tau, phospho-Tau, AbPP, AbPP-Ab, ChAT, and AChE levels in brain tissue. Early limited exposure
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Tylcholine receptor binding in the cerebellum and brainstem [103]. In previous studies using a mouse model of dietinduced obesity [45,46], we showed that chronic HFD feeding causes brain insulin resistance [46]. Similarly, herein we demonstrated that the HFD-fed rats had reduced levels of brain IRS-1 mRNA, which would have been sufficient to cause brain insulin resistance due to impaired transmiss