School of Animal Sciences

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https://hdl.handle.net/10919/111086
The School of Animal Sciences merged Dairy Science and Animal and Poultry Science in 2022.

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Browsing School of Animal Sciences by Subject "0606 Physiology"

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    Glioma-induced peritumoral hyperexcitability in a pediatric glioma model
    Chaunsali, Lata; Tewari, Bhanu P.; Gallucci, Allison; Thompson, Emily G.; Savoia, Andrew; Feld, Noah; Campbell, Susan L. (Wiley, 2020-10-01)
    Epileptic seizures are among the most common presenting symptom in patients with glioma. The etiology of glioma-related seizures is complex and not completely understood. Studies using adult glioma patient tissue and adult glioma mouse models, show that neurons adjacent to the tumor mass, peritumoral neurons, are hyperexcitable and contribute to seizures. Although it is established that there are phenotypic and genotypic distinctions in gliomas from adult and pediatric patients, it is unknown whether these established differences in pediatric glioma biology and the microenvironment in which these glioma cells harbor, the developing brain, differentially impacts surrounding neurons. In the present study, we examine the effect of patient-derived pediatric glioma cells on the function of peritumoral neurons using two pediatric glioma models. Pediatric glioma cells were intracranially injected into the cerebrum of postnatal days 2 and 3 (p2/3) mouse pups for 7 days. Electrophysiological recordings showed that cortical layer 2/3 peritumoral neurons exhibited significant differences in their intrinsic properties compared to those of sham control neurons. Peritumoral neurons fired significantly more action potentials in response to smaller current injection and exhibited a depolarization block in response to higher current injection. The threshold for eliciting an action potential and pharmacologically induced epileptiform activity was lower in peritumoral neurons compared to sham. Our findings suggest that pediatric glioma cells increase excitability in the developing peritumoral neurons by exhibiting early onset of depolarization block, which was not previously observed in adult glioma peritumoral neurons.
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    Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity
    Shi, Hao; Munk, Alexander; Nielsen, Thomas S.; Daughtry, Morgan R.; Larsson, Louise; Li, Shize; Hoyer, Kasper F.; Geisler, Hannah W.; Sulek, Karolina; Kjobsted, Rasmus; Fisher, Taylor; Andersen, Marianne M.; Shen, Zhengxing; Hansen, Ulrik K.; England, Eric M.; Cheng, Zhiyong; Hojlund, Kurt; Wojtaszewski, Jorgen FP P.; Yang, Xiaoyong; Hulver, Matthew W.; Helm, Richard F.; Treebak, Jonas T.; Gerrard, David E. (Elsevier, 2018-05-01)
    Objective: Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle. Methods: We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique and tissue-specific glucose uptake was subsequently evaluated. Tissues were used for histology, qPCR, Western blot, co-immunoprecipitation, and chromatin immunoprecipitation analyses. Results: We found elevated levels of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated glycolytic enzyme activities in skeletal muscle. Moreover, enhanced glucose uptake was also observed in white adipose tissue that was browner than that of WT mice. Interestingly, mKO mice had elevated mRNA levels of Il15 in skeletal muscle and increased circulating IL-15 levels. We found that OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating Enhancer of Zeste Homolog 2 (EZH2). Conclusions: Elevated muscle O-GlcNAc levels paralleled insulin resistance and type 2 diabetes in humans. Moreover, OGT-mediated signaling is necessary for proper skeletal muscle metabolism and whole-body energy homeostasis, and our data highlight O-GlcNAcylation as a potential target for ameliorating metabolic disorders.