Abstract #3923
Hyperpolarized [1-13C]pyruvate detects neuronal metabolic impairment in glucose transporter and pyruvate kinase deficient mice
Caroline Guglielmetti1,2, Huihui Li3, Yoshitaka Sei3, Lydia Le Page1,2, Lauren Schields3,4, Brice Tiret1,2, Xiao Gao1,2,5, Iris Lo3, Talya Dayton6, Jeffrey Rathmell7, Matthew Vander Heiden6,8, Ken Nakamura3,4,9,10, and Myriam Chaumeil1,2,4,5
1Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States, 2Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 3Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, United States, 4Graduate Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA, United States, 5UCSF/UCB Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA, United States, 6Koch Institute for Integrative Cancer Research and the Department of Biology, Massachusetts Institute of Technology, Boston, MA, United States, 7Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Nashville, TN, United States, 8Dana-Farber Cancer Institute, Boston, MA, United States, 9Department of Neurology, University of California San Francisco, San Francisco, CA, United States, 10Graduate Program in Neuroscience, University of California San Francisco, San Francisco, CA, United States
Synopsis
Keywords: Hyperpolarized MR (Non-Gas), NeuroWe generated mice with deletion of the glucose transporter 3 (GLUT3cKO) or pyruvate kinase 1 (PKM1cKO) in CA1 hippocampal neurons. GLUT3cKO and PKM1cKO mice showed memory impairment. Hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging showed that female, but not male, PKM1cKO mice had increased HP [1-13C]pyruvate-to-lactate conversion, while female GLUT3cKO mice had decreased conversion and brain volume, evaluated by T2-MRI. Fluorine-18-fluorodeoxyglucose ([18F]-FDG) positron emission tomography imaging did not detect changes, highlighting HP [1-13C]pyruvate’s potential to detect downstream alterations in brain glucose metabolism. Altogether, our findings demonstrated that neurons metabolize glucose through glycolysis in vivo, and require glycolysis for normal function.
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