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Abstract #2958

Glial-specific inhibition of TCA cycle in rat, by 1H MRS and 13C MRS

Elise Marie Vinckenbosch 1 , Joo Miguel das Neves Duarte 1,2 , and Rolf Gruetter 1,3

1 Laboratory of functional and metabolic imaging, Ecole Polytechnique Fdrale de Lausanne, Lausanne, Switzerland, 2 Faculty of Biology and Medicine, University of Lausanne, Switzerland, 3 Department of Radiology, University of Lausanne and Geneva, Switzerland

Astrocyte importance in rat brain metabolism was highlighted by inhibiting glial TCA cycle at the level of aconitase with fluoroacetate. Changes in neurochemical profile upon glial-specific inhibition under hyperglycemia were measured by 1HMRS and brain compartmentalized metabolism adaptation was studied by following infused [1,6-13C] glucose degradation with 13C MRS at 14.1T. Glial aconitase inhibition had effects on alanine, lactate, aspartate, glutamate and glutamine brain concentrations. Disruption of ammonia homeostasis may be rescued by glutamine accumulation upon increased substrate supply. In 13C MRS, glial selectivity of fluoroacetate inhibition has been proved and observed glial metabolic failure didnt affect glutamate TCA cycle.

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