The Experts below are selected from a list of 171 Experts worldwide ranked by ideXlab platform

Leif Hertz - One of the best experts on this subject based on the ideXlab platform.

  • Glycogenolysis an astrocyte specific reaction is essential for both astrocytic and neuronal activities involved in learning
    Neuroscience, 2017
    Co-Authors: Leif Hertz, Ye Chen
    Abstract:

    Abstract In brain glycogen, formed from glucose, is degraded (Glycogenolysis) in astrocytes but not in neurons. Although most of the degradation follows the same pathway as glucose, its breakdown product, l -lactate, is released from astrocytes in larger amounts than glucose when Glycogenolysis is activated by noradrenaline. However, this is not the case when Glycogenolysis is activated by high potassium ion (K+) concentrations – possibly because noradrenaline in contrast to high K+ stimulates Glycogenolysis by an increase not only in free cytosolic Ca2+ concentration ([Ca2+]i) but also in cyclic AMP (c-AMP), which may increase the expression of the monocarboxylate transporter through which it is released. Several transmitters activate Glycogenolysis in astrocytes and do so at different time points after training. This stimulation is essential for memory consolidation because Glycogenolysis is necessary for uptake of K+ and stimulates formation of glutamate from glucose, and therefore is needed both for removal of increased extracellular K+ following neuronal excitation (which initially occurs into astrocytes) and for formation of transmitter glutamate and GABA. In addition the released l -lactate has effects on neurons which are essential for learning and for learning-related long-term potentiation (LTP), including induction of the neuronal gene Arc/Arg3.1 and activation of gene cascades mediated by CREB and cofilin. Inhibition of Glycogenolysis blocks learning, LTP and all related molecular events, but all changes can be reversed by injection of l -lactate. The effect of extracellular l -lactate is due to both astrocyte-mediated signaling which activates noradrenergic activity on all brain cells and to a minor uptake, possibly into dendritic spines.

  • roles of astrocytic na k atpase and Glycogenolysis for k homeostasis in mammalian brain
    Journal of Neuroscience Research, 2015
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Niklas J Gerkau, Simone Durry, Christine R Rose, Liang Peng
    Abstract:

    : Neuronal excitation increases extracellular K(+) concentration ([K(+)]o) in vivo and in incubated brain tissue by stimulation of postsynaptic glutamatergic receptors and by channel-mediated K(+) release during action potentials. Convincing evidence exists that subsequent cellular K(+) reuptake occurs by active transport, normally mediated by Na(+),K(+)-ATPase. This enzyme is expressed both in neurons and in astrocytes but is stimulated by elevated [K(+)]o only in astrocytes. This might lead to an initial K(+) uptake in astrocytes, followed by Kir4.1-mediated release and neuronal reuptake. In cell culture experiments, K(+)-stimulated Glycogenolysis is essential for operation of the astrocytic Na(+),K(+)-ATPase resulting from the requirement for Glycogenolysis in a pathway leading to uptake of Na(+) for costimulation of its intracellular sodium-binding site. The astrocytic but not the neuronal Na(+),K(+)-ATPase is additionally stimulated by isoproterenol, a β-adrenergic agonist, but only at nonelevated [K(+)]o. This effect is also Glycogenolysis dependent and might play a role during poststimulatory undershoots. Attempts to replicate dependence on Glycogenolysis for K(+) reuptake in glutamate-stimulated brain slices showed similar [K(+)]o recovery half-lives in the absence and presence of the Glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol. The undershoot was decreased, but to the same extent as an unexpected reduction of peak [K(+)]o increase. A potential explanation for this difference from the cell culture experiments is that astrocytic glutamate uptake might supply the cells with sufficient Na(+). Inhibition of action potential generation by tetrodotoxin caused only a marginal, nonsignificant decrease in stimulated [K(+)]o in brain slices, hindering the evaluation if K(+) reaccumulation after action potential propagation requires Glycogenolysis in this preparation.

  • astrocytic Glycogenolysis mechanisms and functions
    Metabolic Brain Disease, 2015
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Ting Du, Baoman Li, Liang Peng
    Abstract:

    Until the demonstration little more than 20 years ago that Glycogenolysis occurs during normal whisker stimulation Glycogenolysis was regarded as a relatively uninteresting emergency procedure. Since then, a series of important astrocytic functions has been shown to be critically dependent on glycogenolytic activity to support the signaling mechanisms necessary for these functions to operate. This applies to glutamate formation and uptake and to release of ATP as a transmitter, stimulated by other transmitters or elevated K+ concentrations and affecting not only other astrocytes but also most other brain cells. It is also relevant for astrocytic K+ uptake both during the period when the extracellular K+ concentration is still elevated after neuronal excitation, and capable of stimulating glycogenolytic activity, and during the subsequent undershoot after intense neuronal activity, when Glycogenolysis may be stimulated by noradrenaline. Both elevated K+ concentrations and several transmitters, including the β-adrenergic agonist isoproterenol and vasopressin increase free cytosolic Ca2+ concentration in astrocytes, which stimulates phosphorylase kinase so that it activates the transformation of the inactive glycogen phosphorylase a to the active phosphorylase b. Contrary to common belief cyclic AMP plays at most a facilitatory role, and only when free cytosolic Ca2+ concentration is also increased. Cyclic AMP is not increased during activation of Glycogenolysis by either elevated K+ concentrations or the stimulation of the serotonergic 5-HT2B receptor. Not all agents that stimulate Glycogenolysis do so by directly activating phophorylase kinase—some do so by activating processes requiring Glycogenolysis, e.g. for synthesis of glutamate.

  • Roles of astrocytic Na(+),K(+)-ATPase and Glycogenolysis for K(+) homeostasis in mammalian brain.
    Journal of Neuroscience Research, 2014
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Niklas J Gerkau, Simone Durry, Christine R Rose, Liang Peng
    Abstract:

    : Neuronal excitation increases extracellular K(+) concentration ([K(+)]o) in vivo and in incubated brain tissue by stimulation of postsynaptic glutamatergic receptors and by channel-mediated K(+) release during action potentials. Convincing evidence exists that subsequent cellular K(+) reuptake occurs by active transport, normally mediated by Na(+),K(+)-ATPase. This enzyme is expressed both in neurons and in astrocytes but is stimulated by elevated [K(+)]o only in astrocytes. This might lead to an initial K(+) uptake in astrocytes, followed by Kir4.1-mediated release and neuronal reuptake. In cell culture experiments, K(+)-stimulated Glycogenolysis is essential for operation of the astrocytic Na(+),K(+)-ATPase resulting from the requirement for Glycogenolysis in a pathway leading to uptake of Na(+) for costimulation of its intracellular sodium-binding site. The astrocytic but not the neuronal Na(+),K(+)-ATPase is additionally stimulated by isoproterenol, a β-adrenergic agonist, but only at nonelevated [K(+)]o. This effect is also Glycogenolysis dependent and might play a role during poststimulatory undershoots. Attempts to replicate dependence on Glycogenolysis for K(+) reuptake in glutamate-stimulated brain slices showed similar [K(+)]o recovery half-lives in the absence and presence of the Glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol. The undershoot was decreased, but to the same extent as an unexpected reduction of peak [K(+)]o increase. A potential explanation for this difference from the cell culture experiments is that astrocytic glutamate uptake might supply the cells with sufficient Na(+). Inhibition of action potential generation by tetrodotoxin caused only a marginal, nonsignificant decrease in stimulated [K(+)]o in brain slices, hindering the evaluation if K(+) reaccumulation after action potential propagation requires Glycogenolysis in this preparation.

  • serotonin mediation of early memory formation via 5 ht2b receptor induced Glycogenolysis in the day old chick
    Frontiers in Pharmacology, 2014
    Co-Authors: Marie E Gibbs, Leif Hertz
    Abstract:

    Investigation of the effects of serotonin on memory formation in the chick revealed an action on at least two 5HT receptors. Serotonin injected intracerebrally produced a biphasic effect on memory consolidation with enhancement at low doses and inhibition at higher doses. The non-selective 5HT receptor antagonist methiothepin and the selective 5HT2B/C receptor antagonist SB221284 both inhibited memory, suggesting actions of serotonin on at least 2 different receptor subtypes. The 5HT2B/C and astrocyte-specific 5-HT receptor agonists, fluoxetine and paroxetine, enhanced memory and the effect was attributed to Glycogenolysis. Inhibition of Glycogenolysis with a low dose of DAB prevented both serotonin and fluoxetine from enhancing memory during short-term memory but not during intermediate memory. The role of serotonin on the 5HT2B/C receptor appears to involve glycogen breakdown in astrocytes during short-term memory, whereas other published evidence attributes the second period of Glycogenolysis to noradrenaline.

Liang Peng - One of the best experts on this subject based on the ideXlab platform.

  • roles of astrocytic na k atpase and Glycogenolysis for k homeostasis in mammalian brain
    Journal of Neuroscience Research, 2015
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Niklas J Gerkau, Simone Durry, Christine R Rose, Liang Peng
    Abstract:

    : Neuronal excitation increases extracellular K(+) concentration ([K(+)]o) in vivo and in incubated brain tissue by stimulation of postsynaptic glutamatergic receptors and by channel-mediated K(+) release during action potentials. Convincing evidence exists that subsequent cellular K(+) reuptake occurs by active transport, normally mediated by Na(+),K(+)-ATPase. This enzyme is expressed both in neurons and in astrocytes but is stimulated by elevated [K(+)]o only in astrocytes. This might lead to an initial K(+) uptake in astrocytes, followed by Kir4.1-mediated release and neuronal reuptake. In cell culture experiments, K(+)-stimulated Glycogenolysis is essential for operation of the astrocytic Na(+),K(+)-ATPase resulting from the requirement for Glycogenolysis in a pathway leading to uptake of Na(+) for costimulation of its intracellular sodium-binding site. The astrocytic but not the neuronal Na(+),K(+)-ATPase is additionally stimulated by isoproterenol, a β-adrenergic agonist, but only at nonelevated [K(+)]o. This effect is also Glycogenolysis dependent and might play a role during poststimulatory undershoots. Attempts to replicate dependence on Glycogenolysis for K(+) reuptake in glutamate-stimulated brain slices showed similar [K(+)]o recovery half-lives in the absence and presence of the Glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol. The undershoot was decreased, but to the same extent as an unexpected reduction of peak [K(+)]o increase. A potential explanation for this difference from the cell culture experiments is that astrocytic glutamate uptake might supply the cells with sufficient Na(+). Inhibition of action potential generation by tetrodotoxin caused only a marginal, nonsignificant decrease in stimulated [K(+)]o in brain slices, hindering the evaluation if K(+) reaccumulation after action potential propagation requires Glycogenolysis in this preparation.

  • astrocytic Glycogenolysis mechanisms and functions
    Metabolic Brain Disease, 2015
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Ting Du, Baoman Li, Liang Peng
    Abstract:

    Until the demonstration little more than 20 years ago that Glycogenolysis occurs during normal whisker stimulation Glycogenolysis was regarded as a relatively uninteresting emergency procedure. Since then, a series of important astrocytic functions has been shown to be critically dependent on glycogenolytic activity to support the signaling mechanisms necessary for these functions to operate. This applies to glutamate formation and uptake and to release of ATP as a transmitter, stimulated by other transmitters or elevated K+ concentrations and affecting not only other astrocytes but also most other brain cells. It is also relevant for astrocytic K+ uptake both during the period when the extracellular K+ concentration is still elevated after neuronal excitation, and capable of stimulating glycogenolytic activity, and during the subsequent undershoot after intense neuronal activity, when Glycogenolysis may be stimulated by noradrenaline. Both elevated K+ concentrations and several transmitters, including the β-adrenergic agonist isoproterenol and vasopressin increase free cytosolic Ca2+ concentration in astrocytes, which stimulates phosphorylase kinase so that it activates the transformation of the inactive glycogen phosphorylase a to the active phosphorylase b. Contrary to common belief cyclic AMP plays at most a facilitatory role, and only when free cytosolic Ca2+ concentration is also increased. Cyclic AMP is not increased during activation of Glycogenolysis by either elevated K+ concentrations or the stimulation of the serotonergic 5-HT2B receptor. Not all agents that stimulate Glycogenolysis do so by directly activating phophorylase kinase—some do so by activating processes requiring Glycogenolysis, e.g. for synthesis of glutamate.

  • Roles of astrocytic Na(+),K(+)-ATPase and Glycogenolysis for K(+) homeostasis in mammalian brain.
    Journal of Neuroscience Research, 2014
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Niklas J Gerkau, Simone Durry, Christine R Rose, Liang Peng
    Abstract:

    : Neuronal excitation increases extracellular K(+) concentration ([K(+)]o) in vivo and in incubated brain tissue by stimulation of postsynaptic glutamatergic receptors and by channel-mediated K(+) release during action potentials. Convincing evidence exists that subsequent cellular K(+) reuptake occurs by active transport, normally mediated by Na(+),K(+)-ATPase. This enzyme is expressed both in neurons and in astrocytes but is stimulated by elevated [K(+)]o only in astrocytes. This might lead to an initial K(+) uptake in astrocytes, followed by Kir4.1-mediated release and neuronal reuptake. In cell culture experiments, K(+)-stimulated Glycogenolysis is essential for operation of the astrocytic Na(+),K(+)-ATPase resulting from the requirement for Glycogenolysis in a pathway leading to uptake of Na(+) for costimulation of its intracellular sodium-binding site. The astrocytic but not the neuronal Na(+),K(+)-ATPase is additionally stimulated by isoproterenol, a β-adrenergic agonist, but only at nonelevated [K(+)]o. This effect is also Glycogenolysis dependent and might play a role during poststimulatory undershoots. Attempts to replicate dependence on Glycogenolysis for K(+) reuptake in glutamate-stimulated brain slices showed similar [K(+)]o recovery half-lives in the absence and presence of the Glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol. The undershoot was decreased, but to the same extent as an unexpected reduction of peak [K(+)]o increase. A potential explanation for this difference from the cell culture experiments is that astrocytic glutamate uptake might supply the cells with sufficient Na(+). Inhibition of action potential generation by tetrodotoxin caused only a marginal, nonsignificant decrease in stimulated [K(+)]o in brain slices, hindering the evaluation if K(+) reaccumulation after action potential propagation requires Glycogenolysis in this preparation.

  • basic mechanism leading to stimulation of Glycogenolysis by isoproterenol egf elevated extracellular k concentrations or gaba
    Neurochemical Research, 2014
    Co-Authors: Junnan Xu, Dan Song, Leif Hertz, Liang Peng
    Abstract:

    Glycogenolysis, in brain parenchyma an astrocyte-specific process, has changed from being envisaged as an emergency procedure to playing central roles during brain response to whisker stimulation, memory formation, astrocytic K+ uptake and stimulated release of ATP. It is activated by several transmitters and by even very small increases in extracellular K+ concentration, and to be critically dependent upon an increase in free cytosolic Ca2+ concentration ([Ca2+]i), whereas cAMP plays only a facilitatory role together with increased [Ca2+]i. Detailed knowledge about the signaling pathways eliciting Glycogenolysis is therefore of interest and was investigated in the present study in well differentiated cultures of mouse astrocytes. The β-adrenergic agonist isoproterenol stimulated Glycogenolysis by a β1-adrenergic effect, which initiated a pathway in which cAMP/protein kinase A activated a Gi/Gs shift, leading to Ca2+-activated Glycogenolysis. Inhibition of this pathway downstream of cAMP but upstream of the Gi/Gs shift abolished the Glycogenolysis. However, inhibitors operating downstream of the Ca2+-sensitive step, but preventing transactivation-mediated epidermal growth factor (EGF) receptor stimulation, a later step in the activated pathway, also caused inhibition of Glycogenolysis. For this reason the effect of EGF was investigated and it was found to be glycogenolytic. Large increases in extracellular K+ activated Glycogenolysis by a nifedipine-inhibited L-channel opening allowing influx of Ca2+, known to be Glycogenolysis-dependent. Small increases (addition of 5 mM KCl) caused a smaller effect by a similarly Glycogenolysis-reliant opening of an IP3 receptor-dependent ouabain signaling pathway. The same pathway could be activated by GABA (also in brain slices) due to its depolarizing effect in astrocytes.

  • Glycogenolysis and purinergic signaling
    Advances in neurobiology, 2014
    Co-Authors: Leif Hertz, Junnan Xu, Liang Peng
    Abstract:

    Both ATP and glutamate are on one hand essential metabolites in brain and on the other serve a signaling function as transmitters. However, there is the major difference that the flux in the pathway producing transmitter glutamate is comparable to the rate of glucose metabolism in brain, whereas that producing transmitter ATP is orders of magnitude smaller than the metabolic turnover between ATP and ADP. Moreover, de novo glutamate production occurs exclusively in astrocytes, whereas transmitter ATP is produced both in neurons and astrocytes. This chapter deals only with ATP and exclusively with its formation and release in astrocytes, and it focuses on potential associations with Glycogenolysis, which is known to be indispensable for the synthesis of glutamate. Glycogenolysis is dependent upon an increase in free intracellular Ca2+ concentration (Ca2+]i). It can be further stimulated by cAMP, but in contrast to widespread beliefs, cAMP can on its own not induce Glycogenolysis. Astrocytes generate ATP from accumulated adenosine, and this process does not seem to require Glycogenolysis. A minor amount of the generated ATP is utilized as a transmitter, and its synthesis requires the presence of the mainly intracellular nucleoside transporter ENT3. Many transmitters as well as extracellular K+ concentrations high enough to open the voltage-sensitive L-channels for Ca2+ cause a release of transmitter ATP from astrocytes. Adenosine and ATP induce release of ATP by action at several different purinergic receptors. The release evoked by transmitters or elevated K+ concentrations is abolished by DAB, an inhibitor of Glycogenolysis.

Junnan Xu - One of the best experts on this subject based on the ideXlab platform.

  • roles of astrocytic na k atpase and Glycogenolysis for k homeostasis in mammalian brain
    Journal of Neuroscience Research, 2015
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Niklas J Gerkau, Simone Durry, Christine R Rose, Liang Peng
    Abstract:

    : Neuronal excitation increases extracellular K(+) concentration ([K(+)]o) in vivo and in incubated brain tissue by stimulation of postsynaptic glutamatergic receptors and by channel-mediated K(+) release during action potentials. Convincing evidence exists that subsequent cellular K(+) reuptake occurs by active transport, normally mediated by Na(+),K(+)-ATPase. This enzyme is expressed both in neurons and in astrocytes but is stimulated by elevated [K(+)]o only in astrocytes. This might lead to an initial K(+) uptake in astrocytes, followed by Kir4.1-mediated release and neuronal reuptake. In cell culture experiments, K(+)-stimulated Glycogenolysis is essential for operation of the astrocytic Na(+),K(+)-ATPase resulting from the requirement for Glycogenolysis in a pathway leading to uptake of Na(+) for costimulation of its intracellular sodium-binding site. The astrocytic but not the neuronal Na(+),K(+)-ATPase is additionally stimulated by isoproterenol, a β-adrenergic agonist, but only at nonelevated [K(+)]o. This effect is also Glycogenolysis dependent and might play a role during poststimulatory undershoots. Attempts to replicate dependence on Glycogenolysis for K(+) reuptake in glutamate-stimulated brain slices showed similar [K(+)]o recovery half-lives in the absence and presence of the Glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol. The undershoot was decreased, but to the same extent as an unexpected reduction of peak [K(+)]o increase. A potential explanation for this difference from the cell culture experiments is that astrocytic glutamate uptake might supply the cells with sufficient Na(+). Inhibition of action potential generation by tetrodotoxin caused only a marginal, nonsignificant decrease in stimulated [K(+)]o in brain slices, hindering the evaluation if K(+) reaccumulation after action potential propagation requires Glycogenolysis in this preparation.

  • astrocytic Glycogenolysis mechanisms and functions
    Metabolic Brain Disease, 2015
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Ting Du, Baoman Li, Liang Peng
    Abstract:

    Until the demonstration little more than 20 years ago that Glycogenolysis occurs during normal whisker stimulation Glycogenolysis was regarded as a relatively uninteresting emergency procedure. Since then, a series of important astrocytic functions has been shown to be critically dependent on glycogenolytic activity to support the signaling mechanisms necessary for these functions to operate. This applies to glutamate formation and uptake and to release of ATP as a transmitter, stimulated by other transmitters or elevated K+ concentrations and affecting not only other astrocytes but also most other brain cells. It is also relevant for astrocytic K+ uptake both during the period when the extracellular K+ concentration is still elevated after neuronal excitation, and capable of stimulating glycogenolytic activity, and during the subsequent undershoot after intense neuronal activity, when Glycogenolysis may be stimulated by noradrenaline. Both elevated K+ concentrations and several transmitters, including the β-adrenergic agonist isoproterenol and vasopressin increase free cytosolic Ca2+ concentration in astrocytes, which stimulates phosphorylase kinase so that it activates the transformation of the inactive glycogen phosphorylase a to the active phosphorylase b. Contrary to common belief cyclic AMP plays at most a facilitatory role, and only when free cytosolic Ca2+ concentration is also increased. Cyclic AMP is not increased during activation of Glycogenolysis by either elevated K+ concentrations or the stimulation of the serotonergic 5-HT2B receptor. Not all agents that stimulate Glycogenolysis do so by directly activating phophorylase kinase—some do so by activating processes requiring Glycogenolysis, e.g. for synthesis of glutamate.

  • Roles of astrocytic Na(+),K(+)-ATPase and Glycogenolysis for K(+) homeostasis in mammalian brain.
    Journal of Neuroscience Research, 2014
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Niklas J Gerkau, Simone Durry, Christine R Rose, Liang Peng
    Abstract:

    : Neuronal excitation increases extracellular K(+) concentration ([K(+)]o) in vivo and in incubated brain tissue by stimulation of postsynaptic glutamatergic receptors and by channel-mediated K(+) release during action potentials. Convincing evidence exists that subsequent cellular K(+) reuptake occurs by active transport, normally mediated by Na(+),K(+)-ATPase. This enzyme is expressed both in neurons and in astrocytes but is stimulated by elevated [K(+)]o only in astrocytes. This might lead to an initial K(+) uptake in astrocytes, followed by Kir4.1-mediated release and neuronal reuptake. In cell culture experiments, K(+)-stimulated Glycogenolysis is essential for operation of the astrocytic Na(+),K(+)-ATPase resulting from the requirement for Glycogenolysis in a pathway leading to uptake of Na(+) for costimulation of its intracellular sodium-binding site. The astrocytic but not the neuronal Na(+),K(+)-ATPase is additionally stimulated by isoproterenol, a β-adrenergic agonist, but only at nonelevated [K(+)]o. This effect is also Glycogenolysis dependent and might play a role during poststimulatory undershoots. Attempts to replicate dependence on Glycogenolysis for K(+) reuptake in glutamate-stimulated brain slices showed similar [K(+)]o recovery half-lives in the absence and presence of the Glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol. The undershoot was decreased, but to the same extent as an unexpected reduction of peak [K(+)]o increase. A potential explanation for this difference from the cell culture experiments is that astrocytic glutamate uptake might supply the cells with sufficient Na(+). Inhibition of action potential generation by tetrodotoxin caused only a marginal, nonsignificant decrease in stimulated [K(+)]o in brain slices, hindering the evaluation if K(+) reaccumulation after action potential propagation requires Glycogenolysis in this preparation.

  • basic mechanism leading to stimulation of Glycogenolysis by isoproterenol egf elevated extracellular k concentrations or gaba
    Neurochemical Research, 2014
    Co-Authors: Junnan Xu, Dan Song, Leif Hertz, Liang Peng
    Abstract:

    Glycogenolysis, in brain parenchyma an astrocyte-specific process, has changed from being envisaged as an emergency procedure to playing central roles during brain response to whisker stimulation, memory formation, astrocytic K+ uptake and stimulated release of ATP. It is activated by several transmitters and by even very small increases in extracellular K+ concentration, and to be critically dependent upon an increase in free cytosolic Ca2+ concentration ([Ca2+]i), whereas cAMP plays only a facilitatory role together with increased [Ca2+]i. Detailed knowledge about the signaling pathways eliciting Glycogenolysis is therefore of interest and was investigated in the present study in well differentiated cultures of mouse astrocytes. The β-adrenergic agonist isoproterenol stimulated Glycogenolysis by a β1-adrenergic effect, which initiated a pathway in which cAMP/protein kinase A activated a Gi/Gs shift, leading to Ca2+-activated Glycogenolysis. Inhibition of this pathway downstream of cAMP but upstream of the Gi/Gs shift abolished the Glycogenolysis. However, inhibitors operating downstream of the Ca2+-sensitive step, but preventing transactivation-mediated epidermal growth factor (EGF) receptor stimulation, a later step in the activated pathway, also caused inhibition of Glycogenolysis. For this reason the effect of EGF was investigated and it was found to be glycogenolytic. Large increases in extracellular K+ activated Glycogenolysis by a nifedipine-inhibited L-channel opening allowing influx of Ca2+, known to be Glycogenolysis-dependent. Small increases (addition of 5 mM KCl) caused a smaller effect by a similarly Glycogenolysis-reliant opening of an IP3 receptor-dependent ouabain signaling pathway. The same pathway could be activated by GABA (also in brain slices) due to its depolarizing effect in astrocytes.

  • Glycogenolysis and purinergic signaling
    Advances in neurobiology, 2014
    Co-Authors: Leif Hertz, Junnan Xu, Liang Peng
    Abstract:

    Both ATP and glutamate are on one hand essential metabolites in brain and on the other serve a signaling function as transmitters. However, there is the major difference that the flux in the pathway producing transmitter glutamate is comparable to the rate of glucose metabolism in brain, whereas that producing transmitter ATP is orders of magnitude smaller than the metabolic turnover between ATP and ADP. Moreover, de novo glutamate production occurs exclusively in astrocytes, whereas transmitter ATP is produced both in neurons and astrocytes. This chapter deals only with ATP and exclusively with its formation and release in astrocytes, and it focuses on potential associations with Glycogenolysis, which is known to be indispensable for the synthesis of glutamate. Glycogenolysis is dependent upon an increase in free intracellular Ca2+ concentration (Ca2+]i). It can be further stimulated by cAMP, but in contrast to widespread beliefs, cAMP can on its own not induce Glycogenolysis. Astrocytes generate ATP from accumulated adenosine, and this process does not seem to require Glycogenolysis. A minor amount of the generated ATP is utilized as a transmitter, and its synthesis requires the presence of the mainly intracellular nucleoside transporter ENT3. Many transmitters as well as extracellular K+ concentrations high enough to open the voltage-sensitive L-channels for Ca2+ cause a release of transmitter ATP from astrocytes. Adenosine and ATP induce release of ATP by action at several different purinergic receptors. The release evoked by transmitters or elevated K+ concentrations is abolished by DAB, an inhibitor of Glycogenolysis.

Dan Song - One of the best experts on this subject based on the ideXlab platform.

  • roles of astrocytic na k atpase and Glycogenolysis for k homeostasis in mammalian brain
    Journal of Neuroscience Research, 2015
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Niklas J Gerkau, Simone Durry, Christine R Rose, Liang Peng
    Abstract:

    : Neuronal excitation increases extracellular K(+) concentration ([K(+)]o) in vivo and in incubated brain tissue by stimulation of postsynaptic glutamatergic receptors and by channel-mediated K(+) release during action potentials. Convincing evidence exists that subsequent cellular K(+) reuptake occurs by active transport, normally mediated by Na(+),K(+)-ATPase. This enzyme is expressed both in neurons and in astrocytes but is stimulated by elevated [K(+)]o only in astrocytes. This might lead to an initial K(+) uptake in astrocytes, followed by Kir4.1-mediated release and neuronal reuptake. In cell culture experiments, K(+)-stimulated Glycogenolysis is essential for operation of the astrocytic Na(+),K(+)-ATPase resulting from the requirement for Glycogenolysis in a pathway leading to uptake of Na(+) for costimulation of its intracellular sodium-binding site. The astrocytic but not the neuronal Na(+),K(+)-ATPase is additionally stimulated by isoproterenol, a β-adrenergic agonist, but only at nonelevated [K(+)]o. This effect is also Glycogenolysis dependent and might play a role during poststimulatory undershoots. Attempts to replicate dependence on Glycogenolysis for K(+) reuptake in glutamate-stimulated brain slices showed similar [K(+)]o recovery half-lives in the absence and presence of the Glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol. The undershoot was decreased, but to the same extent as an unexpected reduction of peak [K(+)]o increase. A potential explanation for this difference from the cell culture experiments is that astrocytic glutamate uptake might supply the cells with sufficient Na(+). Inhibition of action potential generation by tetrodotoxin caused only a marginal, nonsignificant decrease in stimulated [K(+)]o in brain slices, hindering the evaluation if K(+) reaccumulation after action potential propagation requires Glycogenolysis in this preparation.

  • astrocytic Glycogenolysis mechanisms and functions
    Metabolic Brain Disease, 2015
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Ting Du, Baoman Li, Liang Peng
    Abstract:

    Until the demonstration little more than 20 years ago that Glycogenolysis occurs during normal whisker stimulation Glycogenolysis was regarded as a relatively uninteresting emergency procedure. Since then, a series of important astrocytic functions has been shown to be critically dependent on glycogenolytic activity to support the signaling mechanisms necessary for these functions to operate. This applies to glutamate formation and uptake and to release of ATP as a transmitter, stimulated by other transmitters or elevated K+ concentrations and affecting not only other astrocytes but also most other brain cells. It is also relevant for astrocytic K+ uptake both during the period when the extracellular K+ concentration is still elevated after neuronal excitation, and capable of stimulating glycogenolytic activity, and during the subsequent undershoot after intense neuronal activity, when Glycogenolysis may be stimulated by noradrenaline. Both elevated K+ concentrations and several transmitters, including the β-adrenergic agonist isoproterenol and vasopressin increase free cytosolic Ca2+ concentration in astrocytes, which stimulates phosphorylase kinase so that it activates the transformation of the inactive glycogen phosphorylase a to the active phosphorylase b. Contrary to common belief cyclic AMP plays at most a facilitatory role, and only when free cytosolic Ca2+ concentration is also increased. Cyclic AMP is not increased during activation of Glycogenolysis by either elevated K+ concentrations or the stimulation of the serotonergic 5-HT2B receptor. Not all agents that stimulate Glycogenolysis do so by directly activating phophorylase kinase—some do so by activating processes requiring Glycogenolysis, e.g. for synthesis of glutamate.

  • Roles of astrocytic Na(+),K(+)-ATPase and Glycogenolysis for K(+) homeostasis in mammalian brain.
    Journal of Neuroscience Research, 2014
    Co-Authors: Leif Hertz, Junnan Xu, Dan Song, Niklas J Gerkau, Simone Durry, Christine R Rose, Liang Peng
    Abstract:

    : Neuronal excitation increases extracellular K(+) concentration ([K(+)]o) in vivo and in incubated brain tissue by stimulation of postsynaptic glutamatergic receptors and by channel-mediated K(+) release during action potentials. Convincing evidence exists that subsequent cellular K(+) reuptake occurs by active transport, normally mediated by Na(+),K(+)-ATPase. This enzyme is expressed both in neurons and in astrocytes but is stimulated by elevated [K(+)]o only in astrocytes. This might lead to an initial K(+) uptake in astrocytes, followed by Kir4.1-mediated release and neuronal reuptake. In cell culture experiments, K(+)-stimulated Glycogenolysis is essential for operation of the astrocytic Na(+),K(+)-ATPase resulting from the requirement for Glycogenolysis in a pathway leading to uptake of Na(+) for costimulation of its intracellular sodium-binding site. The astrocytic but not the neuronal Na(+),K(+)-ATPase is additionally stimulated by isoproterenol, a β-adrenergic agonist, but only at nonelevated [K(+)]o. This effect is also Glycogenolysis dependent and might play a role during poststimulatory undershoots. Attempts to replicate dependence on Glycogenolysis for K(+) reuptake in glutamate-stimulated brain slices showed similar [K(+)]o recovery half-lives in the absence and presence of the Glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol. The undershoot was decreased, but to the same extent as an unexpected reduction of peak [K(+)]o increase. A potential explanation for this difference from the cell culture experiments is that astrocytic glutamate uptake might supply the cells with sufficient Na(+). Inhibition of action potential generation by tetrodotoxin caused only a marginal, nonsignificant decrease in stimulated [K(+)]o in brain slices, hindering the evaluation if K(+) reaccumulation after action potential propagation requires Glycogenolysis in this preparation.

  • basic mechanism leading to stimulation of Glycogenolysis by isoproterenol egf elevated extracellular k concentrations or gaba
    Neurochemical Research, 2014
    Co-Authors: Junnan Xu, Dan Song, Leif Hertz, Liang Peng
    Abstract:

    Glycogenolysis, in brain parenchyma an astrocyte-specific process, has changed from being envisaged as an emergency procedure to playing central roles during brain response to whisker stimulation, memory formation, astrocytic K+ uptake and stimulated release of ATP. It is activated by several transmitters and by even very small increases in extracellular K+ concentration, and to be critically dependent upon an increase in free cytosolic Ca2+ concentration ([Ca2+]i), whereas cAMP plays only a facilitatory role together with increased [Ca2+]i. Detailed knowledge about the signaling pathways eliciting Glycogenolysis is therefore of interest and was investigated in the present study in well differentiated cultures of mouse astrocytes. The β-adrenergic agonist isoproterenol stimulated Glycogenolysis by a β1-adrenergic effect, which initiated a pathway in which cAMP/protein kinase A activated a Gi/Gs shift, leading to Ca2+-activated Glycogenolysis. Inhibition of this pathway downstream of cAMP but upstream of the Gi/Gs shift abolished the Glycogenolysis. However, inhibitors operating downstream of the Ca2+-sensitive step, but preventing transactivation-mediated epidermal growth factor (EGF) receptor stimulation, a later step in the activated pathway, also caused inhibition of Glycogenolysis. For this reason the effect of EGF was investigated and it was found to be glycogenolytic. Large increases in extracellular K+ activated Glycogenolysis by a nifedipine-inhibited L-channel opening allowing influx of Ca2+, known to be Glycogenolysis-dependent. Small increases (addition of 5 mM KCl) caused a smaller effect by a similarly Glycogenolysis-reliant opening of an IP3 receptor-dependent ouabain signaling pathway. The same pathway could be activated by GABA (also in brain slices) due to its depolarizing effect in astrocytes.

  • role of Glycogenolysis in stimulation of atp release from cultured mouse astrocytes by transmitters and high k concentrations
    Asn Neuro, 2013
    Co-Authors: Junnan Xu, Dan Song, Leif Hertz, Lijun Zhou, Liang Peng
    Abstract:

    This study investigates the role of Glycogenolysis in stimulated release of ATP as a transmitter from astrocytes. Within the last 20 years our understanding of brain Glycogenolysis has changed from it being a relatively uninteresting process to being a driving force for essential brain functions like production of transmitter glutamate and homoeostasis of potassium ions (K+) after their release from excited neurons. Simultaneously, the importance of astrocytic handling of adenosine, its phosphorylation to ATP and release of some astrocytic ATP, located in vesicles, as an important transmitter has also become to be realized. Among the procedures stimulating Ca2+-dependent release of vesicular ATP are exposure to such transmitters as glutamate and adenosine, which raise intra-astrocytic Ca2+ concentration, or increase of extracellular K+ to a depolarizing level that opens astrocytic L-channels for Ca2+ and thereby also increase intra-astrocytic Ca2+ concentration, a prerequisite for Glycogenolysis. The present study has confirmed and quantitated stimulated ATP release from well differentiated astrocyte cultures by glutamate, adenosine or elevated extracellular K+ concentrations, measured by a luciferin/luciferase reaction. It has also shown that this release is virtually abolished by an inhibitor of Glycogenolysis as well as by inhibitors of transmitter-mediated signaling or of L-channel opening by elevated K+ concentrations.

Robert A. Rizza - One of the best experts on this subject based on the ideXlab platform.

  • Obesity and Type 2 Diabetes Impair Insulin-Induced Suppression of Glycogenolysis as Well as
    2020
    Co-Authors: Gluconeogenesis Basu, Visvanathan Chandramouli, Betty Dicke, Bernard R. Landau, Robert A. Rizza
    Abstract:

    To determine whether the hepatic insulin resistance of obesity and type 2 diabetes is due to impaired insulininduced suppression of Glycogenolysis as well as gluconeogenesis, 10 lean nondiabetic, 10 obese nondiabetic, and 11 obese type 2 diabetic subjects were studied after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Gluconeogenesis and Glycogenolysis were measured using the deuterated water method. Before the clamp, when glucose and insulin concentrations differed among the three groups, gluconeogenesis was higher in the diabetic than in the obese nondiabetic subjects (P < 0.05) and Glycogenolysis was higher in the diabetic than in the lean nondiabetic subjects (P < 0.05). During the clamp, when glucose and insulin concentrations were matched and glucagon concentrations were suppressed, both Glycogenolysis and gluconeogenesis were higher (P< 0.01) in the diabetic versus the obese and lean nondiabetic subjects. Furthermore, Glycogenolysis and gluconeogenesis were higher (P < 0.01) in the obese than in the lean nondiabetic subjects. Plasma free fatty acid concentrations correlated (P < 0.001) with glucose production and gluconeogenesis both before and during the clamp and with Glycogenolysis during the clamp (P < 0.01). We concluded that defects in the regulation of Glycogenolysis as well as gluconeogenesis cause hepatic insulin resistance in obese nondiabetic and type 2 diabetic humans. Diabetes 54:1942–1948, 2005

  • obesity and type 2 diabetes impair insulin induced suppression of Glycogenolysis as well as gluconeogenesis
    Diabetes, 2005
    Co-Authors: Rita Basu, Visvanathan Chandramouli, Betty Dicke, Bernard R. Landau, Robert A. Rizza
    Abstract:

    To determine whether the hepatic insulin resistance of obesity and type 2 diabetes is due to impaired insulin-induced suppression of Glycogenolysis as well as gluconeogenesis, 10 lean nondiabetic, 10 obese nondiabetic, and 11 obese type 2 diabetic subjects were studied after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Gluconeogenesis and Glycogenolysis were measured using the deuterated water method. Before the clamp, when glucose and insulin concentrations differed among the three groups, gluconeogenesis was higher in the diabetic than in the obese nondiabetic subjects ( P P P P P P