1
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
1
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
1
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
1
Agent for RNA extraction and QuantiTect SYBR Green PCR Mix were obtained from Qiagen, Inc (Valencia, CA). The AMV 1st Strand cDNAPostnatal day 3 (P3) Long Evans rat pups (mean body weight 10 g) were given 3 alternate day intra-peritoneal (i.p.) injections of 20 g NDEA or vehicle. Upon weaning, male rats (N = 8-10 per group) were pair-fed for 8 weeks with high fat (HFD) or low fat (LFD) chow diets.
1
S performed using the ABC method, and revealed with DAB (brown precipitate)-see Experimental Procedures. Sections were lightly counterstained with Hematoxylin (blue) to help reveal the tissue architecture. Cerebellar layers: ml = molecular layer; pc = Purkinje cell layer; gc = granule cell layer; wm = white matter. Note focal pc loss in A2, and large zones of pc loss in A3 and A4. (Original Magnif
1
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
1
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
1
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:/