Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures

Gao, Chen; Zhou, Liya; Zhu, Wenqi; Wang, Hongyun; Wang, Ruijuan; He, Yunfei; Li, Zhi-Yun

doi:10.1016/j.neulet.2015.03.062

Cited by 28 publications

(19 citation statements)

References 27 publications

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“…Although myelinating Schwann cells in the peripheral nervous system express MCT4 (Domenech‐Estevez et al, ), MCT4 is not co‐expressed with MBP in oligodendrocytes in the CNS (Rinholm et al, ). Astrocytes express MCT4, and lactate transported via MCT4 from astrocytes contributes to neuronal function (Suzuki et al, ; Gao et al, ). The effects of lactate on cell cycling and differentiation of OPCs were blocked by an MCT inhibitor, 4‐CIN (Fig.…”

Section: Discussionmentioning

confidence: 99%

Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation

Ichihara

Doi

Ryu

et al. 2016

Journal Cellular Physiology

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Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4‐dideoxy‐1,4‐imino‐d‐arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model. Cuprizone induced demyelination in the corpus callosum and remyelination occurred after cuprizone treatment ceased. This remyelination was inhibited by the administration of DAB. To further examine whether lactate affects proliferation or differentiation of OPCs, we cultured mouse primary OPC‐rich cells and analyzed the effect of lactate. Lactate rescued the slowed cell cycling induced by 0.4 mM glucose, as assessed by the BrdU‐positive cell ratio. Lactate also promoted OPC differentiation detected by monitoring the mature oligodendrocyte marker myelin basic protein, in the presence of both 36.6 mM and 0.4 mM glucose. Furthermore, these lactate‐mediated effects were suppressed by the reported monocarboxylate transporter inhibitor, α‐cyano‐4‐hydroxy‐cinnamate. These results suggest that lactate directly promotes the cell cycling rate and differentiation of OPCs, and that glycogen, one of the sources of lactate, contributes to remyelination in vivo. J. Cell. Physiol. 232: 986–995, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation

Ichihara

Doi

Ryu

et al. 2016

Journal Cellular Physiology

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“…Briefly, the standard culture medium was replaced with a glucose‐free Earle's balanced salt solution (EBSS) medium (HyClone), and cells were then placed in a hypoxic humidified incubator flushed with gas mixture of 94% N 2 , 5% CO 2 and 1% O 2 . After 6 h of OGD treatment, cells were cultured in the standard medium and under normoxic conditions for reoxygenation (Gao et al ., ). The drug was left in the culture medium at the beginning of OGD treatment.…”

Section: Methodsmentioning

confidence: 97%

Blocking transient receptor potential vanilloid 2 channel in astrocytes enhances astrocyte‐mediated neuroprotection after oxygen–glucose deprivation and reoxygenation

Zhang

Xiao

et al. 2016

Eur J of Neuroscience

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Astrocytes play important roles in homeostatic regulation in the central nervous system and are reported to influence the outcome of ischemic injury. Regulating Ca signaling of astrocytes is a promising strategy for stroke therapy. Herein, we report for the first time that transient receptor potential vanilloid 2 (TRPV2), a Ca -permeable channel that is important in osmotic balance regulation, expresses in rat cortical astrocytes by immunofluorescence. Moreover, oxygen-glucose deprivation and reoxygenation (OGD/R) treatment enhanced the expression. The TRPV2 is functional because Ca imaging showed that activating the TRPV2 channel in cultured astrocytes increased intracellular Ca level and the increment of intracellular Ca level expanded when astrocytes were treated with OGD/R. Staining with 5-ethynyl-2'-deoxyuridine (EdU) revealed that while blocking the TRPV2, it promoted the proliferation of astrocytes. Additionally, blocking the TRPV2 in astrocytes increased the synthesis of nerve growth factor (NGF) mRNA and the secretion of NGF by real-time PCR and enzyme-linked immunosorbent assay respectively. We further found that the increased secretion of NGF could be reversed by c-JunN-terminalkinase (JNK) inhibitor and blocking the TRPV2 caused the phosphorylation of JNK. These indicated that blocking the TRPV2 induced NGF secretion via the mitogen-activated protein kinase (MAPK)-JNK signaling pathway. As the promoted proliferation of astrocytes and secretion of NGF were reported to have neuroprotective effects in the early stage of stroke, we concluded that targeting the TRPV2 channel in astrocytes might be a potential new therapeutic strategy in ischemic stroke.

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“…It has been reported, for example, that oxygen- and glucose-deprivation (OGD) increases cell death in cultured neurons, and up-regulates expression of MCT4 in astrocytes. If, however, cell cultures are exposed to MCT4- or MCT2-specific siRNAs, thus significantly reducing their expression, neuronal cell death increases, unless lactate is added to the culture medium before OGD [ 43 ]. Moreover, expression of MCTs has been found to be perturbed in some pathological conditions, such as epilepsy [ 41 ].…”

Section: Lactate Uptake Across the Blood-brain Barrier And Monocarmentioning

confidence: 99%

Lactate as a Metabolite and a Regulator in the Central Nervous System

Proia

Liegro

Schiera

et al. 2016

IJMS

209

151

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More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even involved in processes as complex as memory formation and neuroprotection. As a matter of fact, exercise offers many benefits for our organisms, and seems to delay brain aging and neurodegeneration. Now, exercise induces the production and release of lactate into the blood which can reach the liver, the heart, and also the brain. Can lactate be a beneficial molecule produced during exercise, and offer neuroprotection? In this review, we summarize what we have known on lactate, discussing the roles that have been attributed to this molecule over time.

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Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures

Cited by 28 publications

References 27 publications

Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation

Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation

Blocking transient receptor potential vanilloid 2 channel in astrocytes enhances astrocyte‐mediated neuroprotection after oxygen–glucose deprivation and reoxygenation

Lactate as a Metabolite and a Regulator in the Central Nervous System

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