Figure 5.

Glutamine uptake is unchanged while its metabolism is higher in the 5xFAD cortex. (A) Uptake and metabolism of [U-¹³C]glutamine (gln) gives rise to ¹³C-enrichment (detected by GC–MS) in glutamate, GABA, and TCA cycle intermediates in acutely isolated slices from (B) cerebral cortex or (C) hippocampus incubated with the labeled substrates for 60 min. ¹³C-enrichment from direct glutamine metabolism is presented as M + X labeling % (X = number of ¹³C-carbons in a given molecule). In the cerebral cortex, overall maintained ¹³C-incorporation in amino acids from [U-¹³C]gln was observed, while higher labeling was detected in most TCA cycle intermediates in 5xFAD mice compared to wild-type (WT) controls, suggesting increased glutaminolysis. In hippocampal slices, a maintained labeling in amino acids and TCA cycle intermediates resulting from [U-¹³C]gln metabolism, with the exception of fumarate, was detected in the 5xFAD mice vs. WT. Values represent mean (±) SD (n  =  4 animals). WT animals are represented as circles, while 5xFAD animals are represented as triangles. The statistical significance (determined with Student’s unpaired t-test) is presented with p values above the bars, with significant values in bold.