Central Nervous System; Glutamates; Glutamine; Psychiatry; Nuclear Magnetic Resonance, Biomolecular
Bioimaging Sciences: Magnetic Resonance Research Center | Magnetic Resonance Spectroscopy
Glutamate and GABA are the major excitatory and inhibitory neurotransmitters in the central nervous system and together account for the majority of all of its neurons. Their synaptic actions are maintained through the operation of complex metabolic cycles between neurons and neighboring astroglia. Work in our laboratory is centered on deciphering the mechanism(s) linking glutamate and GABA neurotransmitter cycling to brain activity, and the role of glucose and alternate substrates (e.g., monocarboxylic acids) in this process. Our studies employ nuclear magnetic resonance (NMR) spectroscopy with stable isotope labeling (13C, 15N) and kinetic modeling to study metabolic pathway fluxes in neurons and glia of the intact brain in vivo. This work is being applied to study the role of altered glucose and neurotransmitter metabolism in rodent models of diabetes, depression, and epilepsy. Our laboratory uses Magnetic Resonance Spectroscopy and Imaging (MRS/I) in conjunction with stable 13C-labeled substrates, which can be introduced into the bloodstream in rodents to ‘visualize’ the pathways of brain glucose and energy metabolism and the synthesis of the neurotransmitter amino acids glutamate (excitatory) and GABA (inhibitory).
Specialized Terms: NMR; 1H NMR; 13C NMR; In vivo brain metabolism; Glutamate; Gamma-aminobutyrate; Glutamine; Neuron-glial trafficking
Extensive Research Description
- NMR studies to elucidate the role of glucose and alternate fuel substrates in support of brain activity and glutamate/GABA/glutamine cycling in diabetes and mood disorders.
- NMR studies of GABA synthesis in the brain
- Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, Sanacora G. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Mol Psych. 2008 Sep 30. [Epub ahead of print]
- Chowdhury GM, Gupta M, Gibson KM, Patel AB, Behar KL. Altered cerebral glucose and acetate metabolism in succinic semialdehyde dehydrogenase-deficient mice: evidence for glial dysfunction and reduced glutamate/glutamine cycling. J Neurochem. 2007 Dec;103(5):2077-91. Epub 2007 Sep 13.
- Chowdhury GM, Patel AB, Mason GF, Rothman DL, Behar KL. Glutamatergic and GABAergic neurotransmitter cycling and energy metabolism in rat cerebral cortex during postnatal development. J Cereb Blood Flow Metab. 2007 Dec;27(12):1895-907. Epub 2007 Apr 18.
- Patel AB, de Graaf RA, Martin DL, Battaglioli G, Behar KL. Evidence that GAD65 mediates increased GABA synthesis during intense neuronal activity in vivo. J Neurochem. 2006 Apr;97(2):385-96. Epub 2006 Mar 15.
- Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL, Shulman RG. Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J Cereb Blood Flow Metab. 2006 Jul;26(7):865-77. Epub 2006 Jan 11.