Forebrain cellular bioenergetics in neonatal mice.

BACKGROUND: Hypoglycemia occurs frequently in the neonate and may result in neurologic dysfunction. Its impact on the kinetics of cellular respiration and bioenergetics in the neonatal brain remains to be explored.

AIMS: Develop murine model to investigate the effects of hypoglycemia on neonatal brain bioenergetics.

STUDY DESIGN: Forebrain fragments were excised from euthanized BALB/c pups aged <24 hours to 14 days. We measured cellular respiration (μM O2 min-1.mg-1) in phosphate-buffered saline with and without glucose, using phosphorescence oxygen analyzer, as well as cellular adenosine triphosphate (ATP, nmol.mg-1) using the luciferin-luciferase system.

RESULTS: In the presence of glucose, although cellular respiration was 11% lower in pups ≤3 days compared to those 3- 14 days old (0.48 vs. 0.54), that difference was not statistically significant (p = 0.14). Respiration driven by endogenous metabolic fuels (without added glucose) was 16% lower in pups ≤3 days compared to those 3- 14 days (0.35 vs. 0.42, p = 0.03), confirming their increased dependency on exogenous glucose. Although cellular ATP was similar between the two age groups (14.9 vs. 11.2, p = 0.32), the ATP content was more severely depleted without added glucose in the younger pups, especially in the presence of the cytochrome c oxidase inhibitor cyanide. The first-order rate constant of cellular ATP decay (hydrolysis) was 44% lower in 2-day-old pups compared to 14-day-old mice (0.43 vs. 0.77 min-1, p = 0.03).

CONCLUSIONS: Forebrain cellular respiration and ATP consumption are lower in young pups than older mice. In the absence of glucose, the support for these processes is reduced in young pups, explaining their brain hypersensitivity to hypoglycemia.