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Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate–glutamine cycle in the tree shrew visual cortex

Sonnay, Sarah LU ; Poirot, Jordan; Just, Nathalie; Clerc, Anne Catherine; Gruetter, Rolf; Rainer, Gregor and Duarte, João M.N. LU (2018) In GLIA 66(3). p.477-491
Abstract

Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate–glutamine cycle (VNT) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation. After identifying the activated... (More)

Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate–glutamine cycle (VNT) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation. After identifying the activated cortical volume by blood oxygenation level-dependent functional magnetic resonance imaging, 1H MRS was performed to measure stimulation-induced variations in metabolite concentrations. Relative to baseline, stimulation of cortical activity for 20 min caused a reduction of glucose concentration by −0.34 ± 0.09 µmol/g (p < 0.001), as well as a −9% ± 1% decrease of the ratio of phosphocreatine-to-creatine (p < 0.05). Then 13C MRS during [1,6-13C]glucose infusion was employed to measure fluxes of energy metabolism. Stimulation of glutamatergic activity, as indicated by a 20% increase of VNT, resulted in increased TCA cycle rates in neurons by 12% ((VTCA n, p < 0.001), p < 0.001) and in astrocytes by 24% ((VTCA g, p = 0.007). We further observed linear relationships between VNT and both VTCA n and VTCA g. Altogether, these results suggest that in the tree shrew primary visual cortex glutamatergic neurotransmission is linked to overall glucose oxidation and to mitochondrial metabolism in both neurons and astrocytes.

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organization
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Contribution to journal
publication status
published
subject
keywords
C, cortical energy metabolism, fMRI, MRS, stimulation
in
GLIA
volume
66
issue
3
pages
15 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:85040649564
ISSN
0894-1491
DOI
language
English
LU publication?
yes
id
daf012d7-1304-4519-8bb1-ac82a34973b3
date added to LUP
2018-01-30 07:18:37
date last changed
2018-05-29 11:30:10
@article{daf012d7-1304-4519-8bb1-ac82a34973b3,
  abstract     = {<p>Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate–glutamine cycle (V<sub>NT</sub>) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation. After identifying the activated cortical volume by blood oxygenation level-dependent functional magnetic resonance imaging, <sup>1</sup>H MRS was performed to measure stimulation-induced variations in metabolite concentrations. Relative to baseline, stimulation of cortical activity for 20 min caused a reduction of glucose concentration by −0.34 ± 0.09 µmol/g (p &lt; 0.001), as well as a −9% ± 1% decrease of the ratio of phosphocreatine-to-creatine (p &lt; 0.05). Then <sup>13</sup>C MRS during [1,6-<sup>13</sup>C]glucose infusion was employed to measure fluxes of energy metabolism. Stimulation of glutamatergic activity, as indicated by a 20% increase of V<sub>NT</sub>, resulted in increased TCA cycle rates in neurons by 12% ((V<sub>TCA</sub> <sup>n</sup>, p &lt; 0.001), p &lt; 0.001) and in astrocytes by 24% ((V<sub>TCA</sub> <sup>g</sup>, p = 0.007). We further observed linear relationships between V<sub>NT</sub> and both V<sub>TCA</sub> <sup>n</sup> and V<sub>TCA</sub> <sup>g</sup>. Altogether, these results suggest that in the tree shrew primary visual cortex glutamatergic neurotransmission is linked to overall glucose oxidation and to mitochondrial metabolism in both neurons and astrocytes.</p>},
  author       = {Sonnay, Sarah and Poirot, Jordan and Just, Nathalie and Clerc, Anne Catherine and Gruetter, Rolf and Rainer, Gregor and Duarte, João M.N.},
  issn         = {0894-1491},
  keyword      = {C,cortical energy metabolism,fMRI,MRS,stimulation},
  language     = {eng},
  month        = {03},
  number       = {3},
  pages        = {477--491},
  publisher    = {John Wiley & Sons},
  series       = {GLIA},
  title        = {Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate–glutamine cycle in the tree shrew visual cortex},
  url          = {http://dx.doi.org/},
  volume       = {66},
  year         = {2018},
}