Glutamate neurotransmitter release depends on a stable precursor cytosolic glutamate concentration. Loss of glutamate by synaptic release will deplete the nerve terminal cytosolic precursor pool unless compensated for by glutamate reuptake and synthesis. Glial uptake efficiently removes released glutamate from the synaptic cleft in order to maintain a low ECF concentration of glutamate. In vivo and in vitro studies indicate that glutamate taken up by glia is converted to glutamine by glutamine synthetase. Glutamine is released from the glia to the ECF where it is taken up by neurons and converted back to glutamate through the action of glutaminase. Despite the critical role of this glutamate/glutamine cycle for normal brain function, little is known about the rate or regulation of this pathway. Recently we have developed and tested in the rat brain a model of this pathway which allows the rate of the glutamate/glutamine cycle to be measured from C MRS measurements of glutamine isotopic labeling. The primary objective of this grant is to determine the rate of the glutamate/glutamine cycle in normal human cortex. C MRS will be used to measured glutamine and glutamate isotopic labeling from infused [1-13C] and [2-13C] glucose. Key aspects of the proposed model of the glutamate/glutamine cycle will be tested through measuring of the effect of altering plasma ammonia concentration on total and anapleurotic glutamine synthesis in subjects with mild hepatic encephalopathy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS037527-04
Application #
6363921
Study Section
Neurology A Study Section (NEUA)
Program Officer
Fureman, Brandy E
Project Start
1998-04-01
Project End
2003-02-28
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
4
Fiscal Year
2001
Total Cost
$346,448
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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