Lactate Effectively Covers Energy Demands during Neuronal Network Activity in Neonatal Hippocampal Slices

Ivanov, Anton; Mukhtarov, Marat; Bregestovski, Pìotr; Zilberter, Yuri

doi:10.3389/fnene.2011.00002

Cited by 46 publications

(78 citation statements)

References 58 publications

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“…However, the fact that no differences were observed in Up state amplitude, a parameter affected by the level of passive supply of oxygen [41, 55], suggests a similar metabolic demand and supply in slices of both sexes.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in endogenous cortical network activity: spontaneously recurring Up/Down states

Sigalas¹,

Konsolaki²,

Skaliora³

2017

Biol Sex Differ

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BackgroundSeveral molecular and cellular processes in the vertebrate brain exhibit differences between males and females, leading to sexual dimorphism in the formation of neural circuits and brain organization. While studies on large-scale brain networks provide ample evidence for both structural and functional sex differences, smaller-scale local networks have remained largely unexplored. In the current study, we investigate sexual dimorphism in cortical dynamics by means of spontaneous Up/Down states, a type of network activity that is exhibited during slow-wave sleep, quiet wakefulness, and anesthesia and is thought to represent the default activity of the cortex.MethodsUp state activity was monitored by local field potential recordings in coronal brain slices of male and female mice across three ages with distinct secretion profiles of sex hormones: (i) pre-puberty (17–21 days old), (ii) 3–9 adult (months old), and (iii) old (19–24 months old).ResultsFemale mice of all ages exhibited longer and more frequent Up states compared to aged-matched male mice. Power spectrum analysis revealed sex differences in the relative power of Up state events, with female mice showing reduced power in the delta range (1–4 Hz) and increased power in the theta range (4–8 Hz) compared to male mice. No sex differences were found in the characteristics of Up state peak voltage and latency.ConclusionsThe present study revealed for the first time sex differences in intracortical network activity, using an ex vivo paradigm of spontaneously occurring Up/Down states. We report significant sex differences in Up state properties that are already present in pre-puberty animals and are maintained through adulthood and old age.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-017-0143-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Sex differences in endogenous cortical network activity: spontaneously recurring Up/Down states

Sigalas¹,

Konsolaki²,

Skaliora³

2017

Biol Sex Differ

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“…We have shown previously that in both neonatal and adult slices, supplementing glucose in ACSF with pyruvate or lactate improves synaptic function. 18,37 In vivo, the interstitial fluid in neocortex and hippocampus contains B1 to 2 mmol/L of basal glucose and similar concentrations of lactate (for review, Zilberter et al 38 ), and therefore cells are potentially able to utilize a combination of both substrates. It is also possible that in vivo, under specific physiologic conditions, the neuronal metabolism may be shifted toward lactate utilization.…”

Section: Astrocyte-released Lactate Is Unlikely a Preferred Neuronal mentioning

confidence: 99%

Glycolysis and Oxidative Phosphorylation in Neurons and Astrocytes during Network Activity in Hippocampal Slices

Ivanov

Malkov

Waseem

et al. 2013

J Cereb Blood Flow Metab

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106

103

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Network activation triggers a significant energy metabolism increase in both neurons and astrocytes. Questions of the primary neuronal energy substrate (e.g., glucose vs. lactate) as well as the relative contributions of glycolysis and oxidative phosphorylation and their cellular origin (neurons vs. astrocytes) are still a matter of debates. Using simultaneous measurements of electrophysiological and metabolic parameters during synaptic stimulation in hippocampal slices from mature mice, we show that neurons and astrocytes use both glycolysis and oxidative phosphorylation to meet their energy demands. Supplementation or replacement of glucose in artificial cerebrospinal fluid (ACSF) with pyruvate or lactate strongly modifies parameters related to network activity-triggered energy metabolism. These effects are not induced by changes in ATP content, pH i , [Ca 2 þ ] i or accumulation of reactive oxygen species. Our results suggest that during network activation, a significant fraction of NAD(P)H response (its overshoot phase) corresponds to glycolysis and the changes in cytosolic NAD(P)H and mitochondrial FAD are coupled. Our data do not support the hypothesis of a preferential utilization of astrocyte-released lactate by neurons during network activation in slices-instead, we show that during such activity glucose is an effective energy substrate for both neurons and astrocytes. Keywords: astrocytes; energy metabolism; glycolysis; lactate; network activity; neurons INTRODUCTION High cellular energy demands during network activation are met by upregulation of cytosolic glycolysis and mitochondrial oxidative phosphorylation. Mitochondrial metabolism provides most of the ATP but glycolysis is also enhanced and may contribute to the energy production. Journal of Cerebral Blood1-4 For elucidation of the cellular basis of neuroenergetics, measurements of metabolic signals including the oxygen utilization and NAD(P)H/FAD autofluorescence provide valuable information for connecting energy metabolism with neuronal activity. NADH (reduced form) is fluorescent when excited with UV light whereas NAD þ is not, leading to a decrease in observed fluorescence as a result of NADH oxidation. In contrast, FAD (oxidized form) is fluorescent, so the oxidation of FADH 2 to FAD causes an increase in fluorescence. The fluorescence of NADH cannot be separated from that of NADPH and their emission is measured in concert (NAD(P)H). NAD(P)H fluorescence represents a 'mixed' signal since this cofactor can be produced by both glycolysis and mitochondria, whereas FAD fluorescence is entirely mitochondrial. 5,6 Measurements of these parameters in combination with electrophysiological recordings have been used in many studies to monitor the energy status during neuronal activity in brain tissues.Typically, NAD(P)H transients induced by synaptic stimulation have a characteristic biphasic waveform: the initial short dip is followed by a long-lasting overshoot. While there exists a common

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“…In the context of acclimation to cold stress, lactate may represent an important metabolite to support energy metabolism in fish brain. Ivanov and colleagues [70] demonstrated that lactate is an efficient energy substrate to fuel brain aerobic energy metabolism in case of insufficient glucose supply under intense synaptic activity. In this example LDH1 converts lactate to pyruvate and generates cellular NADH pools which represent an important physiological response to neural activation.…”

Section: Discussionmentioning

confidence: 99%

Brain functioning under acute hypothermic stress supported by dynamic monocarboxylate utilization and transport in ectothermic fish

Tseng

Liu

et al. 2014

Front Zool

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Background: The vertebrate brain is a highly energy consuming organ that requires continuous energy provision. Energy metabolism of ectothermic organisms is directly affected by environmental temperature changes and has been demonstrated to affect brain energy balance in fish. Fish were hypothesized to metabolize lactate as an additional energy substrate during acute exposure to energy demanding environmental abiotic fluctuations to support brain functionality. However, to date the pathways of lactate mobilization and transport in the fish brain are not well understood, and may represent a critical physiological feature in ectotherms during acclimation to low temperature.

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Lactate Effectively Covers Energy Demands during Neuronal Network Activity in Neonatal Hippocampal Slices

Cited by 46 publications

References 58 publications

Sex differences in endogenous cortical network activity: spontaneously recurring Up/Down states

Sex differences in endogenous cortical network activity: spontaneously recurring Up/Down states

Glycolysis and Oxidative Phosphorylation in Neurons and Astrocytes during Network Activity in Hippocampal Slices

Brain functioning under acute hypothermic stress supported by dynamic monocarboxylate utilization and transport in ectothermic fish

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