Abstract
Neurons and glial cells exchange energy-rich metabolites and it has been suggested, originally based on in vitro data, that astrocytes provide lactate to glutamatergic synapses ("lactate shuttle"). Here, we have studied astrocytes that lack mitochondrial respiration in vitro and in vivo A novel mouse mutant (GLASTCreERT2::Cox10flox/flox) was generated, in which the administration of tamoxifen causes mutant astrocytes to fail in the assembly of mitochondrial cytochrome c oxidase (COX). Focusing on cerebellar Bergmann glia (BG) cells, which exhibit the highest rate of Cre-mediated recombination, we found a normal density of viable astrocytes even 1 year after tamoxifen-induced Cox10 gene targeting. Our data show that BG cells, and presumably all astrocytes, can survive by aerobic glycolysis for an extended period of time in the absence of glial pathology or unspecific signs of neurodegeneration.SIGNIFICANCE STATEMENT When astrocytes are placed into culture, they import glucose and release lactate, an energy-rich metabolite readily metabolized by neurons. This observation led to the "glia-to-neuron lactate shuttle hypothesis," but in vivo evidence for this hypothesis is weak. To study astroglial energy metabolism and the directionality of lactate flux, we generated conditional Cox10 mouse mutants lacking mitochondrial respiration in astrocytes, which forces these cells to survive by aerobic glycolysis. Here, we report that these mice are fully viable in the absence of any signs of glial or neuronal loss, suggesting that astrocytes are naturally glycolytic cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4231-4242 |
| Number of pages | 12 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Volume | 37 |
| Issue number | 16 |
| DOIs | |
| State | Published - Apr 19 2017 |
Fingerprint
Keywords
- astrocytes
- brain energy metabolism
- glycolysis
- lactate shuttle
- mitochondria
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Respiration-Deficient Astrocytes Survive As Glycolytic Cells In Vivo. / Supplie, Lotti M.; Düking, Tim; Campbell, Graham; Diaz, Francisca; Moraes, Carlos T; Götz, Magdalena; Hamprecht, Bernd; Boretius, Susann; Mahad, Don; Nave, Klaus Armin.
In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 37, No. 16, 19.04.2017, p. 4231-4242.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Respiration-Deficient Astrocytes Survive As Glycolytic Cells In Vivo
AU - Supplie, Lotti M.
AU - Düking, Tim
AU - Campbell, Graham
AU - Diaz, Francisca
AU - Moraes, Carlos T
AU - Götz, Magdalena
AU - Hamprecht, Bernd
AU - Boretius, Susann
AU - Mahad, Don
AU - Nave, Klaus Armin
PY - 2017/4/19
Y1 - 2017/4/19
N2 - Neurons and glial cells exchange energy-rich metabolites and it has been suggested, originally based on in vitro data, that astrocytes provide lactate to glutamatergic synapses ("lactate shuttle"). Here, we have studied astrocytes that lack mitochondrial respiration in vitro and in vivo A novel mouse mutant (GLASTCreERT2::Cox10flox/flox) was generated, in which the administration of tamoxifen causes mutant astrocytes to fail in the assembly of mitochondrial cytochrome c oxidase (COX). Focusing on cerebellar Bergmann glia (BG) cells, which exhibit the highest rate of Cre-mediated recombination, we found a normal density of viable astrocytes even 1 year after tamoxifen-induced Cox10 gene targeting. Our data show that BG cells, and presumably all astrocytes, can survive by aerobic glycolysis for an extended period of time in the absence of glial pathology or unspecific signs of neurodegeneration.SIGNIFICANCE STATEMENT When astrocytes are placed into culture, they import glucose and release lactate, an energy-rich metabolite readily metabolized by neurons. This observation led to the "glia-to-neuron lactate shuttle hypothesis," but in vivo evidence for this hypothesis is weak. To study astroglial energy metabolism and the directionality of lactate flux, we generated conditional Cox10 mouse mutants lacking mitochondrial respiration in astrocytes, which forces these cells to survive by aerobic glycolysis. Here, we report that these mice are fully viable in the absence of any signs of glial or neuronal loss, suggesting that astrocytes are naturally glycolytic cells.
AB - Neurons and glial cells exchange energy-rich metabolites and it has been suggested, originally based on in vitro data, that astrocytes provide lactate to glutamatergic synapses ("lactate shuttle"). Here, we have studied astrocytes that lack mitochondrial respiration in vitro and in vivo A novel mouse mutant (GLASTCreERT2::Cox10flox/flox) was generated, in which the administration of tamoxifen causes mutant astrocytes to fail in the assembly of mitochondrial cytochrome c oxidase (COX). Focusing on cerebellar Bergmann glia (BG) cells, which exhibit the highest rate of Cre-mediated recombination, we found a normal density of viable astrocytes even 1 year after tamoxifen-induced Cox10 gene targeting. Our data show that BG cells, and presumably all astrocytes, can survive by aerobic glycolysis for an extended period of time in the absence of glial pathology or unspecific signs of neurodegeneration.SIGNIFICANCE STATEMENT When astrocytes are placed into culture, they import glucose and release lactate, an energy-rich metabolite readily metabolized by neurons. This observation led to the "glia-to-neuron lactate shuttle hypothesis," but in vivo evidence for this hypothesis is weak. To study astroglial energy metabolism and the directionality of lactate flux, we generated conditional Cox10 mouse mutants lacking mitochondrial respiration in astrocytes, which forces these cells to survive by aerobic glycolysis. Here, we report that these mice are fully viable in the absence of any signs of glial or neuronal loss, suggesting that astrocytes are naturally glycolytic cells.
KW - astrocytes
KW - brain energy metabolism
KW - glycolysis
KW - lactate shuttle
KW - mitochondria
UR - http://www.scopus.com/inward/record.url?scp=85021308466&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021308466&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0756-16.2017
DO - 10.1523/JNEUROSCI.0756-16.2017
M3 - Article
VL - 37
SP - 4231
EP - 4242
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 16
ER -