Document Detail

Glutamate metabolism is impaired in transgenic mice with tau hyperphosphorylation.
MedLine Citation:
PMID:  23340677     Owner:  NLM     Status:  MEDLINE    
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-(13)C]glucose and the astrocytic substrate [1,2-(13)C]acetate. Hippocampus and cerebral cortex extracts were analyzed using (1)H and (13)C 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 (13)C label derived from [1-(13)C]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.
Linn Hege Nilsen; Caroline Rae; Lars M Ittner; Jürgen Götz; Ursula Sonnewald
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-23
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-02     Completed Date:  2013-06-28     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  684-91     Citation Subset:  IM    
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MeSH Terms
Acetates / metabolism
Astrocytes / metabolism*
Cerebellar Cortex / metabolism
Dementia / metabolism
Glucose / metabolism
Glutamic Acid / metabolism*
Hippocampus / metabolism
Mice, Transgenic
Neurons / metabolism*
Neurotransmitter Agents / metabolism*
gamma-Aminobutyric Acid / metabolism*
tau Proteins / genetics*,  metabolism
Reg. No./Substance:
0/Acetates; 0/Neurotransmitter Agents; 0/tau Proteins; 3KX376GY7L/Glutamic Acid; 56-12-2/gamma-Aminobutyric Acid; IY9XDZ35W2/Glucose

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