Metabolic Maturation of the Human Brain From Birth Through Adolescence: Insights From In Vivo Magnetic Resonance Spectroscopy

Abstract

Between birth and late adolescence, the human brain undergoes exponential maturational changes. Using in vivo magnetic resonance spectroscopy, we determined the developmental profile for 6 metabolites in 5 distinct brain regions based on spectra from 309 children from 0 to 18 years of age. The concentrations of N-acetyl-aspartate (an indicator for adult-type neurons and axons), creatine (energy metabolite), and glutamate (excitatory neurotransmitter) increased rapidly between birth and 3 months, a period of rapid axonal growth and synapse formation. Myo-inositol, implicated in cell signaling and a precursor of membrane phospholipid, as well as an osmolyte and astrocyte marker, declined rapidly during this period. Choline, a membrane metabolite and indicator for de novo myelin and cell membrane synthesis, peaked from birth until approximately 3 months, and then declined gradually, reaching a plateau at early childhood. Similarly, taurine, involved in neuronal excitability, synaptic potentiation, and osmoregulation, was high until approximately 3 months and thereafter declined. These data indicate that the first 3 months of postnatal life are a critical period of rapid metabolic changes in the development of the human brain. This study of the developmental profiles of the major brain metabolites provides essential baseline information for future analyses of the pediatric health and disease.

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

“…As a different methodology for assessing the development of metabolism in the brain, magnetic resonance spectroscopy has been used to determine the developmental profiles of metabolites, such as a marker of axonal and neuronal development, an energy metabolite, and a membrane metabolite, and indicated that the period between birth and 3 mo of age is an immensely active period in metabolite development (54). A comparison of metabolic maturation in preterm-born infants with that of term infants further showed that the metabolic maturation in preterm-born infants, at term equivalence, preceded development in term infants but then, progressed at a slower pace and trajectory (55).…”

MR Imaging-Detectable Metabolic Alterations in Attention Deficit/Hyperactivity Disorder: From Preclinical to Clinical Studies

“…16,17 MR spectroscopy provides a snapshot of these neurochemical alterations and can also be useful in tracking the progress of a neurologic and/or psychiatric disease in longitudinal studies. Several metabolism alterations have indeed been detected in psychiatric disorders such as schizophrenia, 18 depression, bipolar disorder, 19 and autism spectrum disorder.…”

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

“…In humans, levels of myo-inositol decrease over the first 5 years of life, coincident with colonization and stabilization of the intestinal microbiota. 83,84,120 To extend this further, a recent study conducted transcriptional and metabolomics analyses during mouse conventionalization and found positive correlations between measured metabolites and related host metabolic genes. Furthermore, the data suggest that myo-inositol levels decrease upon conventionalization, suggesting a role for the microbiota in regulating these levels.…”

“…Nevertheless, data from human and mouse studies can be combined to start building hypotheses. For example, a recent study measured important brain metabolites from birth to adolescence, 120 some of which are exclusively part of human metabolism (e.g., N-acetylaspartate) and others that are acquired through diet and/or, potentially, the intestinal microbiota (e.g., myo-inositol). In humans, levels of myo-inositol decrease over the first 5 years of life, coincident with colonization and stabilization of the intestinal microbiota.…”