Substrate Utilization and Brain Development

Cremer, Jill E.

doi:10.1038/jcbfm.1982.45

Cited by 167 publications

(107 citation statements)

References 78 publications

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“…Under nor mal conditions during development, the brain in most species extracts ketone bodies in direct pro portion to their plasma concentrations (Jones, 1979;Cremer, 1982), and exhibits a pattern of utilization that is much less regionally heterogeneous than for glucose utilization (Miller, 1986). In the present study, even if all of the BHB available in plasma were fully utilized by the brain, the oxidative equiv alent would only be about 10% of that from glucose.…”

Section: Methodological Considerationsmentioning

confidence: 57%

“…The concern arises be cause of the ability of many species to utilize alter nate substrates (e.g., ketone bodies, lactate, and amino acids) as an energy source by the brain dur ing development (Jones, 1979;Cremer, 1982). In the developing rat, ketone bodies contribute signifi cantly to energy expenditure by the brain, and therefore lCMRglc measurements cannot readily be used to estimate total cerebral energy demand dur ing development (Nehlig et al, 1988).…”

Section: Methodological Considerationsmentioning

confidence: 99%

“…In the present study, even if all of the BHB available in plasma were fully utilized by the brain, the oxidative equiv alent would only be about 10% of that from glucose. Furthermore, the lowest BHB levels during devel opment in the kitten (indeed, lower than adult val ues) were at the earliest time points (1, 7, and 15 days), which is in contrast to the high plasma ke tone body levels at early developmental time points in species that utilize significant amounts of these substances for the production of cerebral energy (Jones, 1979;Cremer, 1982). Our results, therefore, indicate that BHB is probably not of major impor tance as a fuel for brain energy production in young kittens.…”

Section: Methodological Considerationsmentioning

confidence: 99%

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Metabolic Maturation of the Brain: A Study of Local Cerebral Glucose Utilization in the Developing Cat

Chugani

Hovda

Villablanca

et al. 1991

J Cereb Blood Flow Metab

117

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Summary: Previously, using positron emission tomogra phy (PET), we showed that local cerebral metabolic rates for glucose (lCMRglc) in children undergo dynamic mat urational trends before reaching adult values. In order to develop an animal model that can be used to explore the biological significance of the different segments of the lCMRglc maturational curve, we measured lCMRglc in kit tens at various stages of postnatal development and in adult cats using quantitative [14C]2-deoxyglucose autora diography. In the kitten, very low lCMRg1c levels (0.14 to 0. 53 f.Lmol min -I g -I ) were seen during the first 15 days of life, with phylogenetically older brain regions being generally more metabolically mature than newer struc tures. After 15 days of age, many brain regions (particu larly telencephalic structures) underwent sharp increases of lCMRglc to reach, or exceed, adult rates by 60 days. This developmental period (15 to 60 days) corresponds to the time of rapid synaptic proliferation known to occur in the cat. At 90 and 120 days, a slight decline in lCMRglc Using positron emission tomography (PET), we have previously described the distribution and ab solute rates of local cerebral glucose utilization in the normal human brain from birth to adulthood (Chugani and Phelps, 1986;Chugani et al., 1987 Abbreviations used: BHB, f3-hydroxybutyrate ; 2DG, 2-deoxyglucose; PET, positron emission tomography . 35was observed, but this was followed by a second, larger peak occurring at about 180 days, when sexual matura tion occurs in the cat. Only after 180 days did ICMRglc decrease to reach final adult values (0.21 to 2.04 f.Lmol min -I g -I ) . In general, there was good correlation be tween the metabolic maturation of various neuroanatom ical regions and the emergence of behaviors mediated by the specific region. At least in the kitten visual cortex, which has been extensively studied with respect to de velopmental plasticity, the "critical period" corre sponded to that portion of the lCMRg1c maturational curve surrounding the 60-day metabolic peak. These nor mal maturational ICMRglc data will serve as baseline val ues with which to compare anatomical and metabolic plasticity changes induced by age-related lesions in the cat. Key Words: Cerebral glucose utilization-Brain de velopment-Positron emission tomography-Auto radiography-Plasticity-Cat.metabolic rates for glucose (lCMR g lc) in most brain areas undergo dynamic maturational changes over a rather protracted period. The typically low neonatal values of ICMR g lc rapidly increase from birth and begin to exceed adult values in the second and third postnatal year. By about 4 years, a plateau is reached that extends until about 9 years; following this, there is a gradual decline in ICMR g lc to reach adult values by the end of the second decade. The relative increase in ICMR g lc over adult values is most pronounced in neocortical regions, which at their peak have over a twofold higher ICMR g lc than corresponding adult values. Phylogenetically older structures (e.g.,...

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Section: Methodological Considerationsmentioning

confidence: 57%

Section: Methodological Considerationsmentioning

confidence: 99%

Section: Methodological Considerationsmentioning

confidence: 99%

See 1 more Smart Citation

Metabolic Maturation of the Brain: A Study of Local Cerebral Glucose Utilization in the Developing Cat

Chugani

Hovda

Villablanca

et al. 1991

J Cereb Blood Flow Metab

117

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“…It is well established that glucose is the almost exclusive fuel in the adult, but not the developing brain [1]. The number of glucose transporters in the BBB, GLUT-1, is low in the neonatal brain and rises sharply after the second postnatal week in the period of neuronal maturation and brain growth spurt [3,34].…”

Section: Glucose Utilisationmentioning

confidence: 99%

“…Although alternative substrates for energy production are of major importance in the developing brain, the presence of glucose is essential [1]. This is in part due to the fact that the pentose phosphate pathway (PPP) requires glucose-6-P.…”

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confidence: 99%

Neuron–Astrocyte Interactions, Pyruvate Carboxylation and the Pentose Phosphate Pathway in the Neonatal Rat Brain

et al. 2013

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Glucose and acetate metabolism and the synthesis of amino acid neurotransmitters, anaplerosis, glutamate-glutamine cycling and the pentose phosphate pathway (PPP) have been extensively investigated in the adult, but not the neonatal rat brain. To do this, 7 day postnatal (P7) rats were injected with [1-C]glucose and [1,2-C]acetate and sacrificed 5, 10, 15, 30 and 45 min later. Adult rats were injected and sacrificed after 15 min. To analyse pyruvate carboxylation and PPP activity during development, P7 rats received [1,2-C]glucose and were sacrificed 30 min later. Brain extracts were analysed using Hand C-NMR spectroscopy. The neonatal brain contained lower levels of glutamate, aspartate and N-acetylaspartate but similar levels of GABA and glutamine compared to adults. Metabolism of [1-C]glucose at the acetyl CoA stage was reduced much more than that of [1,2-C]acetate. The transfer of glutamate from neurons to astrocytes was greatly reduced while transfer of glutamine from astrocytes to glutamatergic neurons was relatively higher compared to adults. However, transport of glutamine from astrocytes to GABAergic neurons was lower. Using [1,2-C]glucose it could be shown that despite much lower pyruvate carboxylation, relatively more pyruvate from glycolysis was directed towards anaplerosis than pyruvate dehydrogenation in astrocytes compared to reports from the adult brain. Moreover, the ratio of PPP/glucose metabolism was higher in P7 compared to adult brain. Our findings indicate that only the part of the glutamateglutamine cycle that transfers glutamine from astrocytes to neurons is operating in the After uptake into the cell, glucose (via pyruvate from glycolysis) and acetate can be converted to the TCA cycle substrate acetyl CoA. It has been reported that glucose oxidation is lower and that the average time the metabolites stay in the TCA cycle before conversion to substances such as neurotransmitters glutamate and thereafter γ-amino butyric acid (GABA) is longer in the neonatal compared to the adult brain [7]. This is in part attributed to the low levels of enzymes for pyruvate metabolism and oxidative glucose metabolism in the postnatal period [8].Pyruvate carboxylase, the brain's exclusive anaplerotic enzyme [9], is present in astrocytes only [10], and is of major importance for glial metabolic support of neurotransmission. Pyruvate carboxylase content is low in the neonatal period and increases 15-fold up to young adult age (postnatal day 30-40) when the level reaches a plateau [8].Most of the glutamate in the brain is found in neurons and is released into the synapse after depolarisation [11]. The ability of astrocytes to take up glutamate from the synapse and convert it into glutamine by the astrocyte specific enzyme glutamine synthetase [12] is vital for normal metabolic homeostasis and as a defence mechanism against excitotoxicity [13]. The subsequent transfer of glutamine from astrocytes to neurons for deamidation to glutamate closes the glutamate-

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Human Brain Evolution: A Question of Solving Key Nutritional and Metabolic Constraints on Mammalian Brain Development

Cunnane

2010

Human Brain Evolution

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Substrate Utilization and Brain Development

Cited by 167 publications

References 78 publications

Metabolic Maturation of the Brain: A Study of Local Cerebral Glucose Utilization in the Developing Cat

Metabolic Maturation of the Brain: A Study of Local Cerebral Glucose Utilization in the Developing Cat

Neuron–Astrocyte Interactions, Pyruvate Carboxylation and the Pentose Phosphate Pathway in the Neonatal Rat Brain

Human Brain Evolution: A Question of Solving Key Nutritional and Metabolic Constraints on Mammalian Brain Development

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