Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen and glucose and an increase in lactate production during conventional rapid brain resection and preservation by liquid nitrogen. In contrast, we show that these postmortem changes are not observed with simultaneous animal sacrifice and in situ fixation with focused, high-power microwave. We further employ microwave fixation to define brain glucose metabolism in the mouse model of streptozotocin-induced type 1 diabetes. Using both total pool and isotope tracing analyses, we identified global glucose hypometabolism in multiple brain regions, evidenced by reduced 13C enrichment into glycogen, glycolysis, and the tricarboxylic acid (TCA) cycle. Reduced glucose metabolism correlated with a marked decrease in GLUT2 expression and several metabolic enzymes in unique brain regions. In conclusion, our study supports the incorporation of microwave fixation for more accurate studies of brain metabolism in rodent models.
Bibliographical noteFunding Information:
This study was supported by National Institutes of Health (NIH) grants R35 NS116824 (M.S.G.), P01 NS097197 (M.S.G.), R01 AG066653 (R.C.S.), and R01 CA266004 (R.C.S.); NIH NIDDK R01 DK122811 (B.N.S.); NIH NINDS R01 NS092552 (B.N.S.); NIH/NCI F99CA264165 (L.E.A.Y.); NIH/NCI training grant T32CA165990 (L.R.C.); and a V-Scholar grant (R.C.S.).
© 2023 The Author(s)
- CP: Metabolism
- brain metabolism
- isotope tracing
- microwave fixation
- regional metabolism
- type 1 diabetes
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Radiology Nuclear Medicine and imaging
- Computer Science Applications