Energy and Amino Acid Neurotransmitter Metabolism in Astrocytes

Waagepetersen, Helle S.; Sonnewald, Ursula; Schousboe, Arne

doi:10.1007/978-0-387-79492-1_7

Cited by 14 publications

(24 citation statements)

References 144 publications

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“…In addition to the decrease in the amount of [4,[5][6][7][8][9][10][11][12][13] C]glutamine, it appears that anaerobic glycolytic activity is augmented after treatment with the subconvulsive dose of kainate as observed by the 50% increase in the cortical content of lactate. As neuronal metabolism was not affected by this dose of kainate, the increased glycolytic metabolism is most likely an astrocytic event.…”

Section: Discussionmentioning

confidence: 96%

“…In this study, we demonstrate that astrocytic metabolism is affected by a subconvulsive dose of kainate while neuronal metabolism is not. This is evident from the lower amount of [4,[5][6][7][8][9][10][11][12][13] C]glutamine labeled from the astrocyte-specific substrate [1,2-13 C]acetate and the increased TCA cycle activity in mice treated with the subconvulsive dose of kainate compared with control animals. In contrast, incorporation of 13 C from [1-13 C]glucose into glutamate, aspartate and GABA, reflecting neuronal metabolism, was unaltered by the subconvulsive dose of kainate.…”

Section: Discussionmentioning

confidence: 99%

“…Seizure severity was graded according to a modified Racine scale. 4,14 Fifteen minutes after kainate injection, the mice were injected intraperitoneally with a combination of [1-13 C]glucose (543 mg/kg) and [1,[2][3][4][5][6][7][8][9][10][11][12][13] C]acetate (504 mg/kg) and after another 15 minutes, the brains of the mice were subjected to microwave fixation at 4 kW for 1.7 seconds (model GA5013, Gerling Applied Engineering, Modesto, CA, USA). This is the most humane euthanization method instantly inactivating proteins in the brain.…”

Section: Metabolic Studiesmentioning

confidence: 99%

“…13 [4,[5][6][7][8][9][10][11][12][13] C]a-ketoglutarate is in rapid equilibrium with [4,[5][6][7][8][9][10][11][12][13] C]glutamate, which is a precursor for [4,[5][6][7][8][9][10][11][12][13] C]glutamine. If [4,[5][6][7][8][9][10][11][12][13] C]a-ketoglutarate remains in the astrocytic TCA cycle for further metabolism via this pathway, it will, after condensation with unlabeled acetyl CoA, give rise to [3-13 C]-and [1,2-13 C]a-ketoglutarate in the subsequent turn, which may give rise to glutamate and glutamine displaying the same labeling patterns. Based on the distinct 13 C labeling in glutamine after the first and second turn of TCA cycle metabolism, a number indicative of astrocytic TCA cycle activity can be calculated by relating the amount of isotopomers generated in the second turn of TCA cycle metabolism to the amount of that generated in the first turn, i.e., ( [1,[2]...…”

Section: Nuclear Magnetic Resonance Spectroscopymentioning

confidence: 99%

“…A combination of [1,2-13 C]acetate and [1-13 C]glucose was injected and subsequent nuclear magnetic resonance spectroscopy of cortical extracts was employed to distinctively map astrocytic and neuronal metabolism. The subconvulsive dose of kainate led to an instantaneous increase in the cortical lactate content, a subsequent reduction in the amount of [4,[5][6][7][8][9][10][11][12][13] C]glutamine and an increase in the calculated astrocytic TCA cycle activity. In contrast, the convulsive dose led to decrements in the cortical content and 13 C labeling of glutamate, glutamine, GABA, and aspartate.…”

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confidence: 97%

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A Subconvulsive Dose of Kainate Selectively Compromises Astrocytic Metabolism in the Mouse Brain In Vivo

Walls

Eyjolfsson

Schousboe

et al. 2014

J Cereb Blood Flow Metab

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Despite the well-established use of kainate as a model for seizure activity and temporal lobe epilepsy, most studies have been performed at doses giving rise to general limbic seizures and have mainly focused on neuronal function. Little is known about the effect of lower doses of kainate on cerebral metabolism and particularly that associated with astrocytes. We investigated astrocytic and neuronal metabolism in the cerebral cortex of adult mice after treatment with saline (controls), a subconvulsive or a mildly convulsive dose of kainate. A combination of [1,2-13 C]acetate and [1-13 C]glucose was injected and subsequent nuclear magnetic resonance spectroscopy of cortical extracts was employed to distinctively map astrocytic and neuronal metabolism. The subconvulsive dose of kainate led to an instantaneous increase in the cortical lactate content, a subsequent reduction in the amount of [4,[5][6][7][8][9][10][11][12][13] C]glutamine and an increase in the calculated astrocytic TCA cycle activity. In contrast, the convulsive dose led to decrements in the cortical content and 13 C labeling of glutamate, glutamine, GABA, and aspartate. Evidence is provided that astrocytic metabolism is affected by a subconvulsive dose of kainate, whereas a higher dose is required to affect neuronal metabolism. The cerebral glycogen content was dose-dependently reduced by kainate supporting a role for glycogen during seizure activity.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Metabolic Studiesmentioning

confidence: 99%

Section: Nuclear Magnetic Resonance Spectroscopymentioning

confidence: 99%

mentioning

confidence: 97%

See 3 more Smart Citations

A Subconvulsive Dose of Kainate Selectively Compromises Astrocytic Metabolism in the Mouse Brain In Vivo

Walls

Eyjolfsson

Schousboe

et al. 2014

J Cereb Blood Flow Metab

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Functional and phenotypic differences of pure populations of stem cell‐derived astrocytes and neuronal precursor cells

Kleiderman

Sá

Teixeira

et al. 2015

Glia

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Availability of homogeneous astrocyte populations would facilitate research concerning cell plasticity (metabolic and transcrip tional adaptations; innate immune responses) and cell cycle reactivation. Current protocols to prepare astrocyte cultures differ in their final content of immature precursor cells, preactivated cells or entirely different cell types. A new method taking care of all these issues would improve research on astrocyte functions. We found here that the exposure of a defined population of pluripotent stem cell derived neural stem cells (NSC) to BMP4 results in pure, nonproliferating astrocyte cultures within 24 48 h. These murine astrocytes generated from embryonic stem cells (mAGES) expressed the positive markers GFAP, aqua porin 4 and GLT 1, supported neuronal function, and acquired innate immune functions such as the response to tumor necro sis factor and interleukin 1. The protocol was applicable to several normal or disease prone pluripotent cell lines, and the corresponding mAGES all exited the cell cycle and lost most of their nestin expression, in contrast to astrocytes generated by serum addition or obtained as primary cultures. Comparative gene expression analysis of mAGES and NSC allowed quantifi cation of differences between the two cell types and a definition of an improved marker set to define astrocytes. Inclusion of several published data sets in this transcriptome comparison revealed the similarity of mAGES with cortical astrocytes in vivo. Metabolic analysis of homogeneous NSC and astrocyte populations revealed distinct neurochemical features: both cell types synthesized glutamine and citrate, but only mature astrocytes released these metabolites. Thus, the homogeneous cultures allowed an improved definition of NSC and astrocyte features.

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