Metabolic control of brain energy and neurotransmitter metabolism

Glutamate (Glu) and g-aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitters in the central nervous system. It is well established that a neuronal-astrocytic neurotransmitter cycle (Glu/Gln and GABA/Gln) exists in the brain. Currently, we are actively involved in the quantification of the glutamate/glutamine (Glu/Gln) cycle and GABA/glutamine (GABA/Gln) cycle fluxes and glucose oxidation in the rat and mouse brain. We use in vivo NMR (¹³C NMR and ¹1H NMR) spectroscopy in conjunction with infusion of ¹³C label substrates (glucose and acetate) to follow the incorporation of label into glutamate, glutamine and GABA. For these study we use 7 T and 11.7 T Bruker Avance spectrometers. The objectives of these studies are as follows:

		To determine the relationship between the neurotransmitter cycle flux (GABA/Gln cycle and Glu/Gln cycle) and glucose oxidation over a wide range of brain activity (from isoelectricity to status epilepticus seizure).
		To understand the regulation of intra-cellular and extra-cellular GABA concentration.
		To measure the turnover of brain glycogen.
		The study cerebral energy metabolism and neurotransmitter cycling in functionally-activated and non-activated tissues of different composition (e.g. cortex and hippocampus).

The outcome of these studies will be beneficial in understanding of the brain energetics and several brain-related disorders such as epilepsy, depression and other neurological and psychiatric disorders.

Researchers :
Anant B. Patel
Robin A. de Graaf
Kevin L. Behar
Douglas L. Rothman
Robert G. Shulman