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Abstract #2936

13 C MRS measures the regional changes in neuronal (Glu/GABA) and astroglial mitochondrial TCA cycle and neurotransmitter cycling of the R6/2 Huntingtons disease mice

Golam M. I. Chowdhury 1 , Larry Park 2 , Oxana Lavrova 2 , Monique Thomas 1 , Xiaoxian Ma 3 , Gerard Sanacora 1 , Douglas L Rothman 3 , and Kevin L Behar 1

1 Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States, 2 CHDI Foundation, Inc, Los Angeles, California, United States, 3 Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, United States

Alterations in brain energy metabolism, including reduced glucose utilization and mitochondrial respiration, is observed in Huntingtons Disease (HD) and HD animal models. 1 H-[ 13 C]-MRS can be readily adapted to measure metabolic pathway flux by use of 13 C -labeled substrates. In this study we measured the flow of 13 C label into glutamate, glutamine and GABA in 6 or 8 week old R6/2 and control mice following timed intravenous infusions of [1,6- 13 C 2 ]glucose or [2- 13 C]acetate. Decreased 13 C labeling was observed at 6 weeks and was more pronounced in 8 week old R6/2 mice indicating impaired neuroenergetics and glutamate and GABA neurotransmitter cycling.

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