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.
D020155:3-Hydroxybutyric Acid; D000109:Acetylcholine / Q000096:biosynthesis / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006885:Hydroxybutyrates / Q000378:metabolism; D008297:Male; D008661:Metabolism, Inborn Errors / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants
D006885:Hydroxybutyrates; D003300:Copper; D002795:Choline O-Acetyltransferase; D005947:Glucose; D000109:Acetylcholine; D020155:3-Hydroxybutyric Acid