Figure 4.

Amino acids derived from acetate metabolism are lower in the cortex but unchanged in the hippocampus in 6M 5xFAD brains. (A) Mitochondrial oxidative metabolism of [U-¹³C]glucose (glc, left axes, orange bars) or [1,2-¹³C]acetate (ace, right axes, green bars) gives rise to ¹³C-enrichment (detected by GC–MS) in TCA cycle intermediates and derived amino acids in acutely isolated slices from (B) cerebral cortex or (C) hippocampus incubated with the labeled substrates for 60 min. Molecular carbon labeling (MCL), the weighted average of the carbon labeling in given metabolic intermediates, is presented. [U-¹³C]glucose reflects overall energy metabolism where neurons are the main energy consumers, while [1,2-¹³C]acetate is predominantly metabolized in astrocytes. In the cerebral cortex, overall maintained ¹³C-incorporation in TCA cycle-derived amino acids from [U-¹³C]glucose was observed, while lower MCL in amino acids from [1,2-¹³C]acetate metabolism was found in 5xFAD mice compared to wild-type (WT) controls. In hippocampal slices, a maintained MCL in amino acids resulting from [U-¹³C]glucose and [1,2-¹³C]acetate metabolism 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.