DOSE-DEPENDENT EFFECTS OF OXYGEN ON METABOLISM IN RAT CORTICO-HIPPOCAMPAL BRAIN TISSUE SLICES

by HOLLYFIELD, JENNIFER LYNNE

Studies have shown that 95% oxygen increases neuronal excitability and ROS production. We wanted to investigate the dose-dependent effects of oxygen on brain slice metabolism. We exposed rat brain cortico-hippocampal tissue slices to 0.40, 0.95, and 4.50 ATA O2 for 60 minutes, made dual-phase tissue extracts, and used multi-nuclear NMR experiments to elucidate the slice metabolism. We found that low doses of oxygen may shift metabolism toward anaerobic glycolysis. Elevated lactate suggests this shift, along with elevated ratios of NAD+/NADH which may drive the reactions toward the production of lactate. The results also suggest that high doses of oxygen may cause aerobic glycolysis and oxidative phosphorylation to accelerate. Lower lactate amounts along with a low NAD+/NADH ratio may be driving these reactions towards pyruvate and the TCA cycle and suggest a highly oxidized environment. The 0.40 ATA O2 results suggest a hypoxic environment while the 0.95 and 4.50 ATA O2 results suggest hyperoxic environments that lead to changes in metabolism on both ends of the oxygen spectrum.