Browsing by Subject "Brain metabolism"

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    Brain glycogen serves as a critical glucosamine cache required for protein glycosylation
    (Elsevier, 2021) Sun, Ramon C.; Young, Lyndsay E.A.; Bruntz, Ronald C.; Markussen, Kia H.; Zhou, Zhengqiu; Conroy, Lindsey R.; Hawkinson, Tara R.; Clarke, Harrison A.; Stanback, Alexandra E.; Macedo, Jessica K.A.; Emanuelle, Shane; Brewer, M. Kathryn; Rondon, Alberto L.; Mestas, Annette; Sanders, William C.; Mahalingan, Krishna K.; Tang, Buyun; Chikwana, Vimbai M.; Segvich, Dyann M.; Contreras, Christopher J.; Allenger, Elizabeth J.; Brainson, Christine F.; Johnson, Lance A.; Taylor, Richard E.; Armstrong, Dustin D.; Shaffer, Robert; Waechter, Charles J.; Vander Kooi, Craig W.; DePaoli-Roach, Anna A.; Roach, Peter J.; Hurley, Thomas D.; Drake, Richard R.; Gentry, Matthew S.; Biochemistry and Molecular Biology, School of Medicine
    Glycosylation defects are a hallmark of many nervous system diseases. However, the molecular and metabolic basis for this pathology is not fully understood. In this study, we found that N-linked protein glycosylation in the brain is metabolically channeled to glucosamine metabolism through glycogenolysis. We discovered that glucosamine is an abundant constituent of brain glycogen, which functions as a glucosamine reservoir for multiple glycoconjugates. We demonstrated the enzymatic incorporation of glucosamine into glycogen by glycogen synthase, and the release by glycogen phosphorylase by biochemical and structural methodologies, in primary astrocytes, and in vivo by isotopic tracing and mass spectrometry. Using two mouse models of glycogen storage diseases, we showed that disruption of brain glycogen metabolism causes global decreases in free pools of UDP-N-acetylglucosamine and N-linked protein glycosylation. These findings revealed fundamental biological roles of brain glycogen in protein glycosylation with direct relevance to multiple human diseases of the central nervous system.
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    The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism
    (Elsevier, 2016-12-19) Stage, Eddie; Duran, Tugce; Risacher, Shannon L.; Goukasian, Naira; Do, Triet M.; West, John D.; Wilhalme, Holly; Nho, Kwangsik; Phillips, Meredith; Elashoff, David; Saykin, Andrew J.; Apostolova, Liana G.; Department of Neurology, IU School of Medicine
    INTRODUCTION: We analyzed the effects of the top 20 Alzheimer disease (AD) risk genes on gray-matter density (GMD) and metabolism. METHODS: We ran stepwise linear regression analysis using posterior cingulate hypometabolism and medial temporal GMD as outcomes and all risk variants as predictors while controlling for age, gender, and APOE ε4 genotype. We explored the results in 3D using Statistical Parametric Mapping 8. RESULTS: Significant predictors of brain GMD were SLC24A4/RIN3 in the pooled and mild cognitive impairment (MCI); ZCWPW1 in the MCI; and ABCA7, EPHA1, and INPP5D in the AD groups. Significant predictors of hypometabolism were EPHA1 in the pooled, and SLC24A4/RIN3, NME8, and CD2AP in the normal control group. DISCUSSION: Multiple variants showed associations with GMD and brain metabolism. For most genes, the effects were limited to specific stages of the cognitive continuum, indicating that the genetic influences on brain metabolism and GMD in AD are complex and stage dependent.