Respiration-deficient astrocytes survive as glycolytic cells in vivo

Lotti M. Supplie; Tim Düking; Graham Campbell; Francisca Diaz; Carlos T. Moraes; Magdalena Götz; Bernd Hamprecht; Susann Boretius; Don Mahad; Klaus Armin Nave

doi:10.1523/JNEUROSCI.0756-16.2017

Respiration-deficient astrocytes survive as glycolytic cells in vivo

Lotti M. Supplie, Tim Düking, Graham Campbell, Francisca Diaz, Carlos T. Moraes, Magdalena Götz, Bernd Hamprecht, Susann Boretius, Don Mahad, Klaus Armin Nave

Neurology

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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 (GLAST^CreERT2::Cox10^flox/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.

Original language	English (US)
Pages (from-to)	4231-4242
Number of pages	12
Journal	Journal of Neuroscience
Volume	37
Issue number	16
DOIs	https://doi.org/10.1523/JNEUROSCI.0756-16.2017
State	Published - Apr 19 2017

Keywords

Astrocytes
Brain energy metabolism
Glycolysis
Lactate shuttle
Mitochondria

ASJC Scopus subject areas

Neuroscience(all)

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10.1523/JNEUROSCI.0756-16.2017

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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: Journal of Neuroscience, Vol. 37, No. 16, 19.04.2017, p. 4231-4242.

Research output: Contribution to journal › Article › peer-review

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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.",

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note = "Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (Grants SPP1757 and CNMPB) to K.-A.N. and Progressive MS Alliance Planning Grant to D.M. K.-A.N. holds a European Research Council Advanced Investigator Grant. We thank W. M?bius, T. Ruhwedel, and A. Fahrenholz for support with electron microscopy and histology; T. Pawelz and C. Casper for mice husbandry; P. Brown (Biomolecular Core, University of Edinburgh) for providing Cre expressing lentivirus; and A. Mot for critical reading of the manuscript.",

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