Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline

Hertz, Leif; Gibbs, Marie E.; Dienel, Gerald A.

doi:10.3389/fnins.2014.00261

Cited by 48 publications

(42 citation statements)

References 69 publications

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“…Further, if exogenous lactate is not supplied in such experiments, cultured neurons release lactate to the extracellular medium following depolarization events [22]. This may be consistent with the opinion presented in a recent review by Hertz et al [26] in which both neurons and astrocytes release and accumulate lactate during brain activation until a new intra-extracellular equilibrium is reached; lactate may then be dispersed within the astrocytic syncytium and eventually to some extent be discharged from the brain accounting for the observed uncoupling of glucose and oxygen consumption during brain activation [27]. Further, we have previously found that lactate alone is a poor substrate in terms of supporting synaptic transmission, since re-uptake of released neurotransmitter glutamate in cultured glutamatergic neurons fails [8].…”

Section: Discussionsupporting

confidence: 84%

Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate

et al. 2015

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We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis seems to be negatively affected by the presence of lactate alone, suggesting that glucose is needed to support neuronal energy metabolism during activation.

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Section: Discussionsupporting

confidence: 84%

Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate

et al. 2015

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“…from astrocytes to neurons [33]. It is, however, consistent with a more nuanced view of lactate dynamics where extracellular lactate originates from, and is metabolized by, multiple cell types, where lactate is scattered from the activated brain area via the astrocytic syncytium [34], and where lactate plays roles other than that of an energy substrate, e.g. redox signaling to switch on neuronal plasticity genes [35].…”

Section: Malate Aspartate Shuttle In Isolated Brain Mitochondria and mentioning

confidence: 52%

Fluctuations in Cytosolic Calcium Regulate the Neuronal Malate–Aspartate NADH Shuttle: Implications for Neuronal Energy Metabolism

Satrústegui

Bak

2015

Neurochem Res

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The malate-aspartate NADH shuttle (MAS) operates in neurons and other cells to translocate reducing equivalents from the cytosol to the mitochondrial matrix, thus allowing a continued flux through the glycolytic pathway and metabolism of extracellular lactate. Recent discoveries have taught us that MAS is regulated by fluctuations in cytosolic Ca 2? levels, and that this regulation is required to maintain a tight coupling between neuronal activity and mitochondrial respiration and oxidative phosphorylation. At cytosolic Ca 2? fluctuations below the threshold of the mitochondrial calcium uniporter, there is a positive correlation between Ca 2? and MAS activity; however, if cytosolic Ca 2? increases above the threshold, MAS activity is thought to be reduced by an intricate mechanism. The latter forces the neurons to partly rely on anaerobic glycolysis producing lactate that may be metabolized subsequently, by neurons or other cells. In this review, we will discuss the evidence for Ca 2? -mediated regulation of MAS that have been uncovered over the last decade or so, together with the need for further verification, and examine the metabolic ramifications for neurons.

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“…1e, f). In addition, it is known that lactate is most likely produced and to some extent released from both neurons and astrocytes during brain activation [29]. Therefore, brain lactate could be from blood lactate uptake, …”

Section: Discussionmentioning

confidence: 99%

Brain Glycogen Decreases During Intense Exercise Without Hypoglycemia: The Possible Involvement of Serotonin

et al. 2015

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Brain glycogen stored in astrocytes, a source of lactate as a neuronal energy source, decreases during prolonged exercise with hypoglycemia. However, brain glycogen dynamics during exercise without hypoglycemia remain unknown. Since intense exercise increases brain noradrenaline and serotonin as known inducers for brain glycogenolysis, we hypothesized that brain glycogen decreases with intense exercise not accompanied by hypoglycemia. To test this hypothesis, we employed a well-established acute intense exercise model of swimming in rats. Rats swam for fourteen 20 s bouts with a weight equal to 8 % of their body mass and were sacrificed using high-power (10 kW) microwave irradiation to inactivate brain enzymes for accurate detection of brain glycogen and monoamines. Intense exercise did not alter blood glucose, but did increase blood lactate levels. Immediately after exercise, brain glycogen decreased and brain lactate increased in the hippocampus, cerebellum, cortex, and brainstem. Simultaneously, serotonin turnover in the hippocampus and brainstem mutually increased and were associated with decreased brain glycogen. Intense swimming exercise that does not induce hypoglycemia decreases brain glycogen associated with increased brain lactate, implying an importance of glycogen in brain energetics during intense exercise even without hypoglycemia. Activated serotonergic regulation is a possible underlying mechanism for intense exercise-induced glycogenolysis at least in the hippocampus and brainstem.

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Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline

Cited by 48 publications

References 69 publications

Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate

Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate

Fluctuations in Cytosolic Calcium Regulate the Neuronal Malate–Aspartate NADH Shuttle: Implications for Neuronal Energy Metabolism

Brain Glycogen Decreases During Intense Exercise Without Hypoglycemia: The Possible Involvement of Serotonin

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