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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
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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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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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On-alcoholic steatohepatitis (NASH), and AD [7-13]. The concept that chronic injury caused by exposure to alkylating agents could result in malignancy and/or tissue degeneration is not far-fetched given the facts that: 1) chronic exposures to tobacco nitrosamines cause both lung cancer and emphysema; and 2) treatment with streptozotocin (STZ), a nitrosamine-related compound, causes hepatocellular
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Gs of: 1) increased risk for developing mild cognitive impairment (MCI), dementia, or AD in individuals with T2DM [7,27] or obesity/dyslipidemic disorders [28]; 2) progressive brain insulin resistance andinsulin deficiency in AD [29-32]; 3) cognitive impairment in experimental animal models of T2DM and/or obesity [33,34]; 4) AD-type neurodegeneration and cognitive impairment in experimentally indu
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Elated compound, causes neurodegeneration, whereas peripheral treatment causes DM. Hypothesis: Limited early exposures to nitrosamines that are widely present in the environment, enhance the deleterious effects of high fat intake in promoting T2DM and neurodegeneration. Methods: Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA) by i.p. injection, and upon weaning, they were fed wi
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Urs), rats were sacrificed by i.p. injection of pentobarbital (120 mg/kg). Blood and cerebella were harvested immediately. Blood or serum was used to measure glucose, insulin, cholesterol, triglycerides, and free fatty acid levels, as previously described [45,46]. Cerebella were harvested for histopathological, biochemical, and molecular studies. For histopathology, tissue samples were immersion f
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Fects is clearly warranted. In this regard, guidance may be obtained from what is already known about STZ-induced diseases. STZ, like other N-nitroso compounds, causes cellular injury and disease by functioning as: 1) an alkylating agent and potent mutagen [14]; 2) an inducer of DNA adducts leading to increased apoptosis [23]; 3) a mediator of unscheduled DNA synthesis, triggering cell death [14];