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- Title
Metabolic network analysis of pre-ASD newborns and 5-year-old children with autism spectrum disorder.
- Authors
Lingampelly, Sai Sachin; Naviaux, Jane C.; Heuer, Luke S.; Monk, Jonathan M.; Li, Kefeng; Wang, Lin; Haapanen, Lori; Kelland, Chelsea A.; Van de Water, Judy; Naviaux, Robert K.
- Abstract
Classical metabolomic and new metabolic network methods were used to study the developmental features of autism spectrum disorder (ASD) in newborns (n = 205) and 5-year-old children (n = 53). Eighty percent of the metabolic impact in ASD was caused by 14 shared biochemical pathways that led to decreased anti-inflammatory and antioxidant defenses, and to increased physiologic stress molecules like lactate, glycerol, cholesterol, and ceramides. CIRCOS plots and a new metabolic network parameter, V ° net, revealed differences in both the kind and degree of network connectivity. Of 50 biochemical pathways and 450 polar and lipid metabolites examined, the developmental regulation of the purine network was most changed. Purine network hub analysis revealed a 17-fold reversal in typically developing children. This purine network reversal did not occur in ASD. These results revealed previously unknown metabolic phenotypes, identified new developmental states of the metabolic correlation network, and underscored the role of mitochondrial functional changes, purine metabolism, and purinergic signaling in autism spectrum disorder. Developmental changes from birth to 5-years in ASD were associated with a normal physiologic response to chronic excitatory, ATP-related signaling. An inhibitory reversal in this network occurred during typical development that did not occur in ASD.
- Subjects
CHILDREN with autism spectrum disorders; AUTISM spectrum disorders; NEWBORN infants; PURINERGIC receptors; NETWORK hubs; GLYCERIN
- Publication
Communications Biology, 2024, Vol 7, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-024-06102-y