Lactate, 3-hydroxybutyrate, and glucose as substrates for the early postnatal rat brain

Dombrowski, George J.; Swiatek, Kenneth R.; Chao, Kuen-Lan

doi:10.1007/bf00964877

Cited by 129 publications

(86 citation statements)

References 42 publications

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“…However, transport over the BBB does not appear to be a limiting factor since the amount and % enrichment of glucose in the brain on postnatal day 7 detected in the present study were similar to levels published for the adult brain [27,35]. After entry, a low glucose utilisation rate in P6 rat brain has been reported [36]. In agreement with this lower glycolytic activity was shown directly in the present study by the lower levels of C incorporation from [1-C]glucose at all time-points in lactate and alanine compared to data published for the adult brain [27,35].…”

Section: Glucose Utilisationsupporting

confidence: 88%

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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Section: Glucose Utilisationsupporting

confidence: 88%

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

et al. 2013

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“…After birth, lactate present in high amounts in the blood circulation provides an important energy source for the brain (2,40). In addition, ketone bodies formed by the hepatic oxidation of milk-derived fat are also significant energy substrates for the brain during the preweaning period in rodents (23,39).…”

Section: Switching Of Transporters From Mct1 To Glut1 During Developimentioning

confidence: 99%

“…In addition, ketone bodies formed by the hepatic oxidation of milk-derived fat are also significant energy substrates for the brain during the preweaning period in rodents (23,39). Lactate and ketone body utilization in the brain is very high during the suckling period but decreases after weaning to reach adult values (1,2,14,21,23). In parallel with this energy utility, a higher expression of MCT1 in the microvessels of the brain is observed during suckling in rodents (8,19,25) and declines with weaning, being accompanied by the predominant expression of GLUT1 in the postweaning period (39).…”

Section: Switching Of Transporters From Mct1 To Glut1 During Developimentioning

confidence: 99%

“…Folies represent alternative energy substrates under particular conditions with a decreased utility of glucose, including diabetes and prolonged starvation. The contribution of monocarboxylates to energy supply is also important in neonatal periods, as represented by the neonatal brain (2,14,21). Animal cells take up and excrete the monocarboxylate anions by means of proton-coupled monocarboxylate transporters (MCTs) in an electroneutral manner (5,6).…”

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confidence: 99%

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Histochemical demonstration of a monocarboxylate transporter in the mouse perineurium with special reference to GLUT1

et al. 2008

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Peripheral nerves express GLUT1 in both endoneurial blood vessels and the perineurium and utilize glucose as a major energy substrate, as does the brain. However, under conditions of a reduced utilization of glucose, the brain is dependent upon monocarboxylates such as ketone bodies and lactate, being accompanied by an elevated expression of a monocarboxylate transporter (MCT1) in the blood-brain barrier. The present immunohistochemical study aimed to examine the expression of MCT1 in the peripheral nerves of mice. MCT1 immunoreactivity was found in the perineurial sheath and colocalized with GLUT1, while the endoneurial blood vessels expressed GLUT1 only. An intense expression of MCT1 in the perineurium was confirmed by Western blot and in situ hybridization analyses. Ultrastructurally, the MCT1 and GLUT1 immunoreactivities in the thick perineurium showed an intensity gradient decreasing towards the innermost layer. In neonates, the MCT1 immunoreactivity in the perineurium was intense, while the GLUT1 immunoreactivity was faint or absent. These findings suggest that peripheral nerves depend on monocarboxylates as a major energy source and that MCT1 in the perineurium is responsible for the supply of monocarboxylates to nerve fibers and Schwann cells.

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“…Bars 20 μm (b, f), 5 mm (d) the brain. Lactate and ketone body utilization in the brain is very high during the suckling period but decreases after weaning (5,6,15,24,26). In parallel with this energy demand, a higher expression of MCT1 in the vascular endothelium of the brain is observed during suckling in rodents (12,21,30,35).…”

Section: Discussionmentioning

confidence: 99%

Intensified expressions of a monocarboxylate transporter in consistently renewing tissues of the mouse

2011

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Monocarboxylates-lactate and ketone bodies-can compensate for glucose as energy sources under certain physical conditions. To identify the main energy source used in self-renewing tissues, expression profiles of monocarboxylate transporters (MCTs) were mainly investigated immunohistochemically in the gastrointestinal tract, skin, and bone marrow of mice, with reference to glucose transporters. In the small intestine, MCT1-immunoreactive epithelial cells accumulated in crypts with a selective immunolabeling along the basolateral membrane of cells. BrdU-labeled dividing cells were included in the cryptal MCT1-immunoreactive foci. The skin displayed an intense and extensive immunoreactivity for MCT1 in the hair bulge, which gives rise to the epidermis, hair, and sebaceous gland. The stratified squamous epithelium in the esophagus contained MCT1-immunoreactive cells in the basal layer but frequently lacked GLUT1-immunoreactive cells. The bone marrow was largely immunoreactive for MCT1 but not for GLUT1, suggesting the active production and utilization of monocarboxylates for hematopoiesis under hypoxic conditions. These findings support the idea that monocarboxylates are favorite energy sources in self-renewing tissues.Mammals use two kinds of energy substrates, glucose and monocarboxylates. The latter includes lactate, acetate, ketone bodies, and others. These monocarboxylates, which are intermediate metabolites, provide a "ready-to-use" fuel in most cells or are converted into glucose (gluconeogenesis) and fatty acids (lipogenesis). They can compensate for glucose as an energy source under several physical conditions such as fasting, diabetes, and the neonatal period (16,35). The production of monocarboxylates does not need oxygen; therefore, they may be evolutionally older (more primitive) energy substrates than glucose, since the concentration of O 2 was low in ancient times. Hypoxic conditions exist in the bone marrow and tumors where proliferative activities are high, and some signals of hypoxia stimulate the cell proliferation (7, 9). There is a possibility that the monocarboxylates produced by anaerobic glycolysis are favorite energy sources for cell growth in selfrenewing tissues and tumors. In mammals, a membrane-bound transporter family mediates the uptake and excretion of monocarboxylates. A representative transporter for monocarboxylates is the monocarboxylate transporter (MCT) and the classified SLC16 gene family. MCT is a H + -coupled, electroneutral, and bi-directional transporter composed of twelve transmembrane domains with intracellular N and C terminal domains (10, 11). To date, fourteen MCT isoforms-each having a unique distribution and different sequence homology-have been identified in mammals, though only four (MCT1-MCT4) have been demonstrated experimentally to facilitate the proton-linked transport of metabolically important monocarboxylates (14,23). It is possible to evaluate the existence of a monocarbox-

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Lactate, 3-hydroxybutyrate, and glucose as substrates for the early postnatal rat brain

Cited by 129 publications

References 42 publications

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

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

Histochemical demonstration of a monocarboxylate transporter in the mouse perineurium with special reference to GLUT1

Intensified expressions of a monocarboxylate transporter in consistently renewing tissues of the mouse

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