Glutamate metabolism is impaired in transgenic mice with tau hyperphosphorylation

Nilsen, Linn Hege, Rae, Caroline, Ittner, Lars M., Goetz, Juergen and Sonnewald, Ursula (2013) Glutamate metabolism is impaired in transgenic mice with tau hyperphosphorylation. Journal of Cerebral Blood Flow and Metabolism, 33 5: 684-691. doi:10.1038/jcbfm.2012.212


Author Nilsen, Linn Hege
Rae, Caroline
Ittner, Lars M.
Goetz, Juergen
Sonnewald, Ursula
Title Glutamate metabolism is impaired in transgenic mice with tau hyperphosphorylation
Journal name Journal of Cerebral Blood Flow and Metabolism   Check publisher's open access policy
ISSN 0271-678X
1559-7016
Publication date 2013-05
Sub-type Article (original research)
DOI 10.1038/jcbfm.2012.212
Volume 33
Issue 5
Start page 684
End page 691
Total pages 8
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Collection year 2014
Language eng
Formatted abstract
In neurodegenerative diseases including Alzheimer’s disease and frontotemporal dementia, the protein tau is hyperphosphorylated and eventually aggregates to develop neurofibrillary tangles. Here, the consequences of tau hyperphosphorylation on both neuronal and astrocytic metabolism and amino-acid neurotransmitter homeostasis were assessed in transgenic mice expressing the pathogenic mutation P301L in the human tau gene (pR5 mice) compared with nontransgenic littermate controls. Mice were injected with the neuronal and astrocytic substrate [1-13C]glucose and the astrocytic substrate [1,2-13C]acetate. Hippocampus and cerebral cortex extracts were analyzed using 1H and 13C nuclear magnetic resonance spectroscopy, gas chromatography–mass spectrometry and high-performance liquid chromatography. The glutamate level was reduced in the hippocampus of pR5 mice, accompanied by reduced incorporation of 13C label derived from [1-13C]glucose in glutamate. In the cerebral cortex, glucose utilization as well as turnover of glutamate, glutamine, and GABA, were increased. This was accompanied by a relative increase in production of glutamate via the pyruvate carboxylation pathway in cortex. Overall, we revealed that astrocytes as well as glutamatergic and GABAergic neurons in the cortex of pR5 mice were in a hypermetabolic state, whereas in the hippocampus, where expression levels of mutant human tau are the highest, glutamate homeostasis was impaired.
Keyword Astrocytes
Dementia
Gaba
Glutamate
MR spectroscopy
Neurotransmitters
Cerebral Glucose-Metabolism
Glial-Neuronal Interactions
Paired Helical Filament
Frontotemporal Dementia
Alzheimers-Disease
P301L Tau
Neurochemical Profile
In-Vivo
Fdg-Pet
Protein
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 19 times in Thomson Reuters Web of Science Article | Citations
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