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Unraveling the complex metabolic nature of astrocytes.

Bouzier-Sore AK, Pellerin L - Front Cell Neurosci (2013)

Bottom Line: Moreover, this unusual metabolic feature was found to be modulated by glutamatergic activity constituting the initial step of the neurometabolic coupling mechanism.Several approaches, including biochemical measurements in cultured cells, genetic screening, dynamic cell imaging, nuclear magnetic resonance spectroscopy and mathematical modeling, have provided further insights into the intrinsic characteristics giving rise to these key features of astrocytes.This review will provide an account of the different results obtained over several decades that contributed to unravel the complex metabolic nature of astrocytes that make this cell type unique.

View Article: PubMed Central - PubMed

Affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS/Université Bordeaux Segalen Bordeaux, France.

ABSTRACT
Since the initial description of astrocytes by neuroanatomists of the nineteenth century, a critical metabolic role for these cells has been suggested in the central nervous system. Nonetheless, it took several technological and conceptual advances over many years before we could start to understand how they fulfill such a role. One of the important and early recognized metabolic function of astrocytes concerns the reuptake and recycling of the neurotransmitter glutamate. But the description of this initial property will be followed by several others including an implication in the supply of energetic substrates to neurons. Indeed, despite the fact that like most eukaryotic non-proliferative cells, astrocytes rely on oxidative metabolism for energy production, they exhibit a prominent aerobic glycolysis capacity. Moreover, this unusual metabolic feature was found to be modulated by glutamatergic activity constituting the initial step of the neurometabolic coupling mechanism. Several approaches, including biochemical measurements in cultured cells, genetic screening, dynamic cell imaging, nuclear magnetic resonance spectroscopy and mathematical modeling, have provided further insights into the intrinsic characteristics giving rise to these key features of astrocytes. This review will provide an account of the different results obtained over several decades that contributed to unravel the complex metabolic nature of astrocytes that make this cell type unique.

No MeSH data available.


(A) Typical 13C-NMR spectrum of rat brain perchloric extract, after perfusion with [1-13C]glucose. (1) Glucose C1α, (2) glucose C1β, 3: glucose C2, C3, C4, C5 and C6, 4: Glu C2, 5:Gln C2, 6: Asp C2, 7: Asp C3, 8: GABA C2, 9: Glu C4, 10: Gln C4, 11: Glu C3, 12: Gln C3, 13: lactate C3 and 14: Ala C3. (B)13C-13C coupling figures allow to distinguish between different isotopomers (example on glutamate C3).
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Figure 1: (A) Typical 13C-NMR spectrum of rat brain perchloric extract, after perfusion with [1-13C]glucose. (1) Glucose C1α, (2) glucose C1β, 3: glucose C2, C3, C4, C5 and C6, 4: Glu C2, 5:Gln C2, 6: Asp C2, 7: Asp C3, 8: GABA C2, 9: Glu C4, 10: Gln C4, 11: Glu C3, 12: Gln C3, 13: lactate C3 and 14: Ala C3. (B)13C-13C coupling figures allow to distinguish between different isotopomers (example on glutamate C3).

Mentions: A large part of evidence that astrocytes do fulfill a metabolic role towards neurons was achieved by nuclear magnetic resonance (NMR) spectroscopy. 13C-NMR spectroscopy in particular is a unique tool to study the metabolism of glucose and metabolic interactions between neurons and astrocytes in the brain. However, sensitivity of the carbon-13 nucleus is low. To overcome these disadvantages, 99%-13C enriched substrates, such as [1-13C]glucose or [2-13C]acetate for example, are used. Added to the cell culture medium, or intravenously injected, this magnetic active isotope will permit analyzing cellular metabolism over time using 13C-NMR spectroscopy. Indeed, all 13C -labeled metabolites derived from the 13C-labeled precursor will be detected on a single 13C-NMR spectrum; each carbon will respectively give a signal (peak) at a different place on the NMR scale depending on their position within every metabolite. (Figure 1A).


Unraveling the complex metabolic nature of astrocytes.

Bouzier-Sore AK, Pellerin L - Front Cell Neurosci (2013)

(A) Typical 13C-NMR spectrum of rat brain perchloric extract, after perfusion with [1-13C]glucose. (1) Glucose C1α, (2) glucose C1β, 3: glucose C2, C3, C4, C5 and C6, 4: Glu C2, 5:Gln C2, 6: Asp C2, 7: Asp C3, 8: GABA C2, 9: Glu C4, 10: Gln C4, 11: Glu C3, 12: Gln C3, 13: lactate C3 and 14: Ala C3. (B)13C-13C coupling figures allow to distinguish between different isotopomers (example on glutamate C3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3795301&req=5

Figure 1: (A) Typical 13C-NMR spectrum of rat brain perchloric extract, after perfusion with [1-13C]glucose. (1) Glucose C1α, (2) glucose C1β, 3: glucose C2, C3, C4, C5 and C6, 4: Glu C2, 5:Gln C2, 6: Asp C2, 7: Asp C3, 8: GABA C2, 9: Glu C4, 10: Gln C4, 11: Glu C3, 12: Gln C3, 13: lactate C3 and 14: Ala C3. (B)13C-13C coupling figures allow to distinguish between different isotopomers (example on glutamate C3).
Mentions: A large part of evidence that astrocytes do fulfill a metabolic role towards neurons was achieved by nuclear magnetic resonance (NMR) spectroscopy. 13C-NMR spectroscopy in particular is a unique tool to study the metabolism of glucose and metabolic interactions between neurons and astrocytes in the brain. However, sensitivity of the carbon-13 nucleus is low. To overcome these disadvantages, 99%-13C enriched substrates, such as [1-13C]glucose or [2-13C]acetate for example, are used. Added to the cell culture medium, or intravenously injected, this magnetic active isotope will permit analyzing cellular metabolism over time using 13C-NMR spectroscopy. Indeed, all 13C -labeled metabolites derived from the 13C-labeled precursor will be detected on a single 13C-NMR spectrum; each carbon will respectively give a signal (peak) at a different place on the NMR scale depending on their position within every metabolite. (Figure 1A).

Bottom Line: Moreover, this unusual metabolic feature was found to be modulated by glutamatergic activity constituting the initial step of the neurometabolic coupling mechanism.Several approaches, including biochemical measurements in cultured cells, genetic screening, dynamic cell imaging, nuclear magnetic resonance spectroscopy and mathematical modeling, have provided further insights into the intrinsic characteristics giving rise to these key features of astrocytes.This review will provide an account of the different results obtained over several decades that contributed to unravel the complex metabolic nature of astrocytes that make this cell type unique.

View Article: PubMed Central - PubMed

Affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS/Université Bordeaux Segalen Bordeaux, France.

ABSTRACT
Since the initial description of astrocytes by neuroanatomists of the nineteenth century, a critical metabolic role for these cells has been suggested in the central nervous system. Nonetheless, it took several technological and conceptual advances over many years before we could start to understand how they fulfill such a role. One of the important and early recognized metabolic function of astrocytes concerns the reuptake and recycling of the neurotransmitter glutamate. But the description of this initial property will be followed by several others including an implication in the supply of energetic substrates to neurons. Indeed, despite the fact that like most eukaryotic non-proliferative cells, astrocytes rely on oxidative metabolism for energy production, they exhibit a prominent aerobic glycolysis capacity. Moreover, this unusual metabolic feature was found to be modulated by glutamatergic activity constituting the initial step of the neurometabolic coupling mechanism. Several approaches, including biochemical measurements in cultured cells, genetic screening, dynamic cell imaging, nuclear magnetic resonance spectroscopy and mathematical modeling, have provided further insights into the intrinsic characteristics giving rise to these key features of astrocytes. This review will provide an account of the different results obtained over several decades that contributed to unravel the complex metabolic nature of astrocytes that make this cell type unique.

No MeSH data available.