The effect of glycogen phosphorolysis on basal glutaminergic transmission

Mozrzymas, Jerzy W.; Szczęsny, Tomasz Jarosław; Rakus, Dariusz

doi:10.1016/j.bbrc.2010.12.033

Cited by 26 publications

(31 citation statements)

References 18 publications

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“…Hippocampal neuron cultures (NC) were prepared from newborn Wistar rats as described previously (Mozrzymas et al, ) with slight modifications. Dissected hippocampi were placed in dissociation medium (DM: 81.8 m M Na 2 SO 4 , 30 m M K 2 SO 4 , 5.8 m M MgCl 2 , 0.25 m M CaCl 2 , 1 m M HEPES, 25 m M glucose, 1 m M kynurenic acid, and 0.001% phenol red) supplemented with 100 U papain and incubated for 30 min at 37 ° C. Then, hippocampal pieces were washed 3 times in DM and in seeding medium (Eagle's Minimum Essential Medium supplemented with 10% FBS, penicillin (100 U/mL), streptomycin (0.1 mg/mL), 1% GlutaMAX, and 1% nonessential amino acids).…”

Section: Methodsmentioning

confidence: 99%

Astrocyte‐neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes

Mamczur

Borsuk

Paszko

et al. 2014

Glia

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Astrocytes releasing glucose- and/or glycogen-derived lactate and glutamine play a crucial role in shaping neuronal function and plasticity. Little is known, however, how metabolic functions of astrocytes, e.g., their ability to degrade glucosyl units, are affected by the presence of neurons. To address this issue we carried out experiments which demonstrated that co-culturing of rat hippocampal astrocytes with neurons significantly elevates the level of mRNA and protein for crucial enzymes of glycolysis (phosphofructokinase, aldolase, and pyruvate kinase), glycogen metabolism (glycogen synthase and glycogen phosphorylase), and glutamine synthetase in astrocytes. Simultaneously, the decrease of the capability of neurons to metabolize glucose and glutamine is observed. We provide evidence that neurons alter the expression of astrocytic enzymes by secretion of as yet unknown molecule(s) into the extracellular fluid. Moreover, our data demonstrate that almost all studied enzymes may localize in astrocytic nuclei and this localization is affected by the co-culturing with neurons which also reduces proliferative activity of astrocytes. Our results provide the first experimental evidence that the astrocyte-neuron crosstalk substantially affects the expression of basal metabolic enzymes in the both types of cells and influences their subcellular localization in astrocytes.

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Section: Methodsmentioning

confidence: 99%

Astrocyte‐neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes

Mamczur

Borsuk

Paszko

et al. 2014

Glia

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“…The most popular interpretation of the ANLS says that the majority of glucose in brain is utilized by astrocytes which convert it into pyruvate which, after reduction to lactate, is released from astrocytes and serves neurons to produce energy in the process of oxidative phosphorylation (Pellerin & Magistretti, 1994;Pellerin & Magistretti, 2012;Serres, Bezancon, Franconi, & Merle, 2004). The second one, which we name here LTP-ANLS, operates during the memory (LTP) formation (Dringen, Gebhardt, & Hamprecht, 1993;Drulis-Fajdasz et al, 2015;Suzuki et al, 2011) and is involved in regulation of miniature postsynaptic potentials (Kaczor, Rakus, & Mozrzymas, 2015;Mozrzymas, Szcze R sny, & Rakus, 2011). The latter mechanism seems to be well documented although the manner/molecular mechanism in which astrocytic glycogen-derived lactate supports LTP and miniature postsynaptic currents is still under investigation.…”

Section: Introductionmentioning

confidence: 99%

Aging‐associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte‐to‐neuron lactate shuttle

Drulis−Fajdasz

Gizak

Wójtowicz

et al. 2018

Glia

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Lactate derived from astrocytic glycogen has been shown to support memory formation in hippocampi of young animals, inhibiting it in old animals. Here we show, using quantitative mass spectrometry‐based proteomics, immunofluorescence, and qPCR that aging is associated with an increase of glycogen metabolism enzymes concentration and shift in their localization from astrocytes to neurons. These changes are accompanied with reorganization of hippocampal energy metabolism which is manifested by elevated capacity of aging neurons to oxidize glucose in glycolysis and mitochondria, and decreased ability for fatty acids utilization. Our observations suggest that astrocyte‐to‐neuron lactate shuttle may operate in young hippocampi, however, during aging neurons become independent on astrocytic lactate and the metabolic crosstalk between the brain's cells is disrupted.

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“…For example, knockout (KO) of brain glycogen synthase impairs hippocampal long‐term potentiation (LTP) and memory consolidation, clearly proving a major role for glycogen in cognitive activities (Duran, Saez, Gruart, Guinovart, & Delgado‐Garcia, ). This conclusion is supported by studies in which inhibition of glycogen phosphorylase in cultured cells, brain slices, or in living brain with different compounds (e.g., 1,4‐dideoxy‐1,4‐imino‐D‐arabinitol (DAB), [R‐R*,S*]‐5‐chloro‐N‐[2‐hydroxy‐3‐(methoxymethylamino)‐3‐oxo‐1‐(phenylmethyl)propyl]‐1H‐indole‐2‐carboxamide (CP‐316,819), isofagomine, 4‐(2‐chlorophenyl)‐1‐ethyl‐1,4‐dihydro‐6‐methyl‐2,3,5‐pyridinetricarboxylic acid (BAY U6751)) also has deleterious effects on glutamatergic neurotransmission, LTP, memory consolidation, and other aspects of neural function (e.g., Drulis‐Fajdasz et al, ; Hertz & Gibbs, ; Mozrzymas, Szczęsny, & Rakus, ; Sickmann, Walls, Schousboe, Bouman, & Waagepetersen, ; Suzuki et al, ; Zhang et al, ). Most of the brain glycogen is contained in astrocytes, and there may be a tendency to ascribe the effects of glycogenolysis impairment to astrocytes.…”

Section: Roles Of Glycogen In Brainmentioning

confidence: 88%

“…©2019 American Physiological Society, with permission Abbreviations. Glc, glucose; Glc-6-P, glucose-6-phosphate; Pyr, pyruvate; PC, pyruvate carboxylase; PDH, pyruvate dehydrogenase; TCA, tricarboxylic acid; Glu, glutamate; Gln, glutamine; V cycle , rate of the glutamate-glutamine cycle; Lac, lactate; ER, endoplasmic reticulum; NE, norepinephrine; 5-HT, 5-hydroxytryptamine (serotonin); β 1 AR, β 1 -adrenergic receptor; GPR81, G-protein-coupled lactate receptor81 also known as HCAR1, hydroxycarboxylic acid receptor1; IC 50 , concentration at which the response is reduced by half; LacR, unidentified lactate receptor; EC 50 , concentration required to produce half maximal response; MAS, malate-aspartate shuttle; MCT, monocarboxylic acid transporter aspects of neural function (e.g., Drulis-Fajdasz et al, 2015;Hertz & Gibbs, 2009;Mozrzymas, Szczęsny, & Rakus, 2011;Sickmann, Walls, Schousboe, Bouman, & Waagepetersen, 2009;Suzuki et al, 2011;Zhang et al, 2016). Most of the brain glycogen is contained in astrocytes, and there may be a tendency to ascribe the effects of glycogenolysis impairment to astrocytes.…”

Section: Neurotransmission and Memorymentioning

confidence: 99%

Does shuttling of glycogen‐derived lactate from astrocytes to neurons take place during neurotransmission and memory consolidation?

Dienel

2019

J of Neuroscience Research

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Glycogen levels in resting brain and its utilization rates during brain activation are high, but the functions fulfilled by glycogenolysis in living brain are poorly understood. Studies in cultured astrocytes have identified glycogen as the preferred fuel to provide ATP for Na+,K+‐ATPase for the uptake of extracellular K+ and for Ca2+‐ATPase to pump Ca2+ into the endoplasmic reticulum. Studies in astrocyte–neuron co‐cultures led to the suggestion that glycogen‐derived lactate is shuttled to neurons as oxidative fuel to support glutamatergic neurotransmission. Furthermore, both knockout of brain glycogen synthase and inhibition of glycogenolysis prior to a memory‐evoking event impair memory consolidation, and shuttling of glycogen‐derived lactate as neuronal fuel was postulated to be required for memory. However, lactate shuttling has not been measured in any of these studies, and procedures to inhibit glycogenolysis and neuronal lactate uptake are not specific. Testable alternative mechanisms to explain the observed findings are proposed: (i) disruption of K+ and Ca2+ homeostasis, (ii) release of gliotransmitters, (iii) imposition of an energy crisis on astrocytes and neurons by inhibition of mitochondrial pyruvate transport by compounds used to block neuronal monocarboxylic acid transporters, and (iv) inhibition of astrocytic filopodial movements that secondarily interfere with glutamate and K+ uptake from the synaptic cleft. Evidence that most pyruvate/lactate derived from glycogen is not oxidized and does not accumulate suggests predominant glycolytic metabolism of glycogen to support astrocytic energy demands. Sparing of blood‐borne glucose for use by neurons is a reasonable explanation for the requirement for glycogenolysis in neurotransmission and memory processing.

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The effect of glycogen phosphorolysis on basal glutaminergic transmission

Cited by 26 publications

References 18 publications

Astrocyte‐neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes

Astrocyte‐neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes

Aging‐associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte‐to‐neuron lactate shuttle

Does shuttling of glycogen‐derived lactate from astrocytes to neurons take place during neurotransmission and memory consolidation?

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