Hypoxia, Brain; Depression; gamma-Aminobutyric Acid; Glutamates; Ketamine; Psychiatry; Stress, Psychological; Diseases
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 process of complex metabolic cycles between neurons and neighboring astroglia. My research mainly focuses on deciphering the mechanism(s) linking glutamate and GABA neurotransmitter cycling to brain activity, and the role of glucose and alternative substrates (e.g., monocarboxylic acids) in this operation. My studies employ nuclear magnetic resonance (NMR) spectroscopy with stable isotope labeling (13C) and kinetic modeling to elucidate metabolic pathway fluxes in neurons and glia of the intact brain in vivo and ex vivo as well. In addition, I have determined the effects of chronic stress on the physiology and molecular biology of the amino acid neurotransmitter systems, especially targeting these systems for drug discovery and development. My other current research is concerned with understanding the role of altered glucose and neurotransmitter metabolism in rodent models of depression, diabetes, and epilepsy.
The major goals of these studies are following:
1. To understand the relationship between neurotransmission and neuroenergetics in the brain
2. To know the rates of glutamatergic and GABAergic neurotransmission
3. To know neuro-glial trafficking in the brain
4. Development of novel diagnostic strategies to improve treatment planning and prognosis of patients with mood and anxiety disorder
5. Exploring the role of cellular toxicity and neuroplasticity in the pathophysiology and treatment of mood disorders
6. To understand the mechanism of hypoxia and brain metabolism and metabolic adaptation
7. To understand the capacity of ketone bodies to replace glucose in support of neuronal function
Specialized Terms: NMR; 13C NMR; in vivo and ex vivo brain metabolism; glutamate; gamma-aminobutyrate; glutamine; neuron-glial trafficking; depression; stress; brain development; drugs discovery; hypoxia; nanotoxicity; ketone bodies; ketamine; antidepressant; riluzole; SSADH
- Chowdhury GMI, Jiang L, Rothman DL, Behar KL. The contribution of ketone bodies to basal and activity-dependent neuronal oxidation in vivo. J Cereb Blood Flow Metab. 2014 Jul;34(7):1233-42.
- de Graaf RA, Chowdhury GMI, Behar KL. Quantification of High-Resolution 1H-[13C] NMR Spectra from Rat Brain Extracts. Anal Chem. 2014 May 20;86(10):5032-8.
- AB Patel, JCK Lai, GMI Chowdhury, F Hyder, DL Rothman, RG Shulman, Behar KL Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5385-90.
- Chowdhury GMI, Behar KL, Cho W, Thomas M, Rothman DL, Sanacora G. 1H-[13C]-NMR Spectroscopy Measures of Ketamine’s Effect on Amino Acid Neurotransmitter Metabolism. Biol Psychiatry. 2012 June ;71(11):1022-1025.
- Robin A. de Graaf, Golam M. I. Chowdhury, Kevin L. Behar. Quantification of High-Resolution 1H NMR Spectra from Rat Brain Extracts. Anal Chem. 2011 Jan 1;83(1):216-24.
- Banasr M, Chowdhury GMI, 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 Psychiatry. 2010 May;15(5):501-11.
- de Graaf RA, Chowdhury GMI, Brown PB, Rothman DL, Behar KL. In Situ 3D MR Metabolic Imaging of Microwave-Irradiated Rodent Brain: A New Tool for Metabolomics Research. J Neurochem. 2009 Apr;109(2):494-501.
- Chowdhury GMI, Banasr M, de Graaf RA, Rothman DL, Behar KL, Sanacora G. Chronic riluzole treatment increase glucose metabolism in rat prefrontal cortex and hippocampus. J Cereb Blood Flow Metab. 2008 Dec;28(12):1892-7.
- Chowdhury GMI, 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.
- Chowdhury GMI, 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.
- Chowdhury GMI, Fujioka T & Nakamura S. Induction and adaptation of Fos Expression in the Rat Brain by two Types of Acute Restraint Stress. Brain Res Bull. 2000 Jun;52(3):171-82.
- Chowdhury GMI, Zhang J, Banasr M, Thomas M, Ma X, Pittman B, Bristow L, Schaeffer E, Duman RS, Rothman DL, Behar KL, Sanacora G. Transiently increased glutamate cycling in rat PFC is associated with rapid onset of antidepressant-like effects. Mol Psychiatry. (Advance online publication 12 April 2016, doi:10.1038/mp.2016.34).