The dentate gyrus differentially metabolizes glucose and alternative fuels during rest and stimulation

Stable isotope tracing in acute hippocampal slices followed by mass spectrometry imaging reveals DGC layer metabolism of alternative fuels, including lactate/pyruvate and β-hydroxybutyrate (βHB), into the TCA cycle under baseline conditions. Brief stimulation with 50 mM KCl causes a rapid decrease in DGC layer ATP, and a preferential increase in glucose metabolism relative to alternative fuel metabolism. Glucose preference occurs even under conditions of fuel com petition. This work achieves broad metabolite coverage from a spatially defined region of physiological tissue, in which metabolic states are rapidly preserved following experimental manipulation. AbstractThe metabolic demands of neuronal activity are both temporally and spatially dynamic, and neurons are particularly sensitive to disruptions in fuel and oxygen supply. Glucose is considered an obligate fuel for supporting brain metabolism. Although alternative fuels are often available, the extent of their contribution to central carbon metabolism remains debated. Differential fuel metabolism likely depends on cell type, location, and activity state, complicating its study. While biosensors provide excellent spatial and temporal information, they are limited to observations of only a few metabolites. On the other hand, mass spectrometry is rich in chemical information, but traditionally relies on cell culture or homogenized tissue samples. Here, we use mass spectrometry imaging (MALDI-MSI) to focus on the fuel me...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research