Hyperpolarized 1-13Cpyruvate detects neuronal metabolic impairment in glucose transporter and pyruvate kinase deficient mice

We 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 1-13Cpyruvate-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 1-13Cpyruvate’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.