In vitro acetylcholine synthesis and oxidative metabolism during development of normal and brindled mouse brain

During early development normal and brindled mouse brain use 3-hydroxy-butyrate preferentially to glucose as a source for biosynthetic carbon units. On postnatal days 5-60, CO2 and acetylcholine production from 3-hydroxybutyrate decrease while that from glucose increases. Glucose metabolism exceeds that of 3-hydroxybutyrate after weaning (day 21). These findings indicate that the immature brain uses 3-hydroxybutyrate to support effectively oxidative metabolism and acetylcholine synthesis. Deficits in oxidative and acetylcholine metabolism occur in the developing brindled mouse, a genetic mutant with a defect in copper homeostasis. In the brindled mouse forebrain and cerebellum, the incorporation of either substrate into CO2 and acetylcholine was decreased 15%, 50% and 80% at days 5, 10 and 15 postnatal, respectively, when compared to the normal littermates. The brindled mouse demonstrates deficits in both oxidative metabolism and acetylcholine synthesis before the appearance of neuropathology.