title: Aerobic glycolysis in the human brain is associated with development and neotenous gene expression.
abstract: Aerobic glycolysis (AG; i.e., nonoxidative metabolism of glucose despite the presence of abundant oxygen) accounts for 10%-12% of glucose used by the adult human brain. AG varies regionally in the resting state. Brain AG may support synaptic growth and remodeling; however, data supporting this hypothesis are sparse. Here, we report on investigations on the role of AG in the human brain. Meta-analysis of prior brain glucose and oxygen metabolism studies demonstrates that AG increases during childhood, precisely when synaptic growth rates are highest. In resting adult humans, AG correlates with the persistence of gene expression typical of infancy (transcriptional neoteny). In brain regions with the highest AG, we find increased gene expression related to synapse formation and growth. In contrast, regions high in oxidative glucose metabolism express genes related to mitochondria and synaptic transmission. Our results suggest that brain AG supports developmental processes, particularly those required for synapse formation and growth.
authors.affiliation: Neuroimaging Laboratories, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA. Electronic address: goyalm@mir.wustl.edu.
authors.forename: Manu S
authors.initials: MS
authors.lastname: Goyal
authors.affiliation: Allen Institute for Brain Science, 551 North 34(th) Street, Seattle, WA 98103, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hawrylycz
authors.affiliation: Allen Institute for Brain Science, 551 North 34(th) Street, Seattle, WA 98103, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Miller
authors.affiliation: Neuroimaging Laboratories, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA.
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.affiliation: Neuroimaging Laboratories, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA. Electronic address: marc@npg.wustl.edu.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Raichle
mesh_terms: D000328:Adult; D000332:Aerobiosis; D001921:Brain / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D063990:Gene Ontology; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D010101:Oxygen Consumption / Q000235:genetics; D013569:Synapses / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D005947:Glucose