Developmental Changes in Brain Glucose, Glycogen, Phosphocreatine, and ATP Levels in DBA/2J and C57BL/6J Mice, and Audiogenic Seizures

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Abstract
Brains of rodents are primarily dependent on ketone bodies as a source of hydrogen for NADH and of acetyl‐CoA during the perinatal period characterized by suckling. A mouse dam begins to wean her pups at about 14 days of age (DOA), the same age at which the brain reaches near‐adult size and begins to shift to dependence on carbohydrate‐derived sources of acetyl‐CoA for normal function. Also at this time, the ear canals open, and mice of some strains become susceptible to audiogenic seizures (AGS). There may be a genetically determined derangement in the orderly transition from one source of brain energy to the other in AGS‐prone mice, with a concomitant brief (days) reduction in the in situ energy reserve during the transition. In mice with a decreased energy reserve, a large energy expenditure within a short period of time (s), such as that induced by a substantial acoustic stimulus to newly opened acoustic pathways, might briefly lead to CNS disorganization before body energy repletion processes may occur, resulting in the onset of an AGS. Since glucose, glycogen, ATP, and phosphocreatine provide the bulk of the brain energy reserve, a developmental study was performed to measure the concentrations of these metabolites in brain tissues of DBA/2J mice (genetically/developmentally susceptible to AGS: onset at 12–14 DOA, peak at 18–21 DOA, rapid decline until 30 DOA, essentially lost by 42 DOA) and in C57BL/6J mice (not developmentally susceptible to AGS). Samples of frontal, temporal, cerebellar, and diencephalic regions were taken from mice 0–44 DOA and assayed. With the exception of higher glycogen levels in both DBA and C57 mice in cerebellar and diencephalic samples 0–16 DOA, no regional differences were found. A decrease in glycogen in all regions was observed in DBA mice 16–30 DOA, which was the inverse of susceptibility to AGS in these mice. This dip was not found in C57 mice. ATP levels were elevated in DBA mice 14–18 DOA, and glucose levels were decreased in DBA mice 24–40 DOA. These data lend support to the hypothesis that lowered brain energy reserves, or lowered access to brain reserves, underlies susceptibility to AGS.