Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation.
Neurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose rem...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5884621?pdf=render |
| _version_ | 1819042906951909376 |
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| author | Courtney Sobieski Natasha Warikoo Hong-Jin Shu Steven Mennerick |
| author_facet | Courtney Sobieski Natasha Warikoo Hong-Jin Shu Steven Mennerick |
| author_sort | Courtney Sobieski |
| collection | DOAJ |
| description | Neurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose removal in the absence of secondary excitotoxicity. Neuronal survival and synaptic transmission were unaffected by prolonged removal of exogenous glucose. Inhibition of lactate transport decreased microculture neuronal survival during concurrent glucose deprivation, suggesting that endogenously released lactate is important for tolerance to glucose deprivation. Tandem depolarization and glucose deprivation also reduced neuronal survival, and trace glucose concentrations afforded neuroprotection. Mass cultures, in contrast to microcultures, were insensitive to depolarizing glucose deprivation, a difference attributable to increased extracellular lactate levels. Removal of local astrocyte support did not reduce survival in response to glucose deprivation or alter evoked excitatory transmission, suggesting that on-demand, local lactate shuttling is not necessary for neuronal tolerance to prolonged glucose removal. Taken together, these data suggest that endogenously produced lactate available globally in the extracellular milieu sustains neurons in the absence of glucose. A better understanding of resilience mechanisms in reduced preparations could lead to therapeutic strategies aimed to bolster these mechanisms in vulnerable neuronal populations. |
| first_indexed | 2024-12-21T09:48:20Z |
| format | Article |
| id | doaj.art-b5b410d8bef348208b6c20593e378a28 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T09:48:20Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b5b410d8bef348208b6c20593e378a282022-12-21T19:08:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01134e019552010.1371/journal.pone.0195520Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation.Courtney SobieskiNatasha WarikooHong-Jin ShuSteven MennerickNeurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose removal in the absence of secondary excitotoxicity. Neuronal survival and synaptic transmission were unaffected by prolonged removal of exogenous glucose. Inhibition of lactate transport decreased microculture neuronal survival during concurrent glucose deprivation, suggesting that endogenously released lactate is important for tolerance to glucose deprivation. Tandem depolarization and glucose deprivation also reduced neuronal survival, and trace glucose concentrations afforded neuroprotection. Mass cultures, in contrast to microcultures, were insensitive to depolarizing glucose deprivation, a difference attributable to increased extracellular lactate levels. Removal of local astrocyte support did not reduce survival in response to glucose deprivation or alter evoked excitatory transmission, suggesting that on-demand, local lactate shuttling is not necessary for neuronal tolerance to prolonged glucose removal. Taken together, these data suggest that endogenously produced lactate available globally in the extracellular milieu sustains neurons in the absence of glucose. A better understanding of resilience mechanisms in reduced preparations could lead to therapeutic strategies aimed to bolster these mechanisms in vulnerable neuronal populations.http://europepmc.org/articles/PMC5884621?pdf=render |
| spellingShingle | Courtney Sobieski Natasha Warikoo Hong-Jin Shu Steven Mennerick Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation. PLoS ONE |
| title | Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation. |
| title_full | Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation. |
| title_fullStr | Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation. |
| title_full_unstemmed | Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation. |
| title_short | Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation. |
| title_sort | ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation |
| url | http://europepmc.org/articles/PMC5884621?pdf=render |
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