Kevin L. Behar, Ph.D.

Associate Professor, Department of Psychiatry, Director of MRRC Neurometabolism Research Laboratory, and Laboratory of Animal Spectroscopy and Metabolomics

Contact

Address:
Yale University, School of Medicine
Magnetic Resonance Research Center
TAC, N151, 300 Cedar Street
New Haven, Connecticut 06520-8043
United States

Email: kevin.behar@yale.edu
Telephone: (203) 737-4121
Fax: (203) 785-6643

Education

University of Iowa, Iowa City, IA B.S. 1979
Yale University, New Haven, CT M.Phil. 1985
Yale University, New Haven, CT Ph.D. 1985
Yale University, New Haven, CT - Postdoc 1985-86

Please click here for Curriculum Vitae

Research Interests

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). Normally, glucose is the major fuel of brain energy metabolism and the primary carbon source in the synthesis of the neurotransmitters glutamate and GABA. Glutamate and GABA are released from active nerve terminals and are removed by rapid transport into surrounding glia. There, glutamate and GABA can be metabolized to glutamine, which is released and transported into neurons where resynthesis of the neurotransmitters can occur. These substrate cycles (glutamate/glutamine and GABA/glutamine) establish metabolic and functional communication between neurons and astroglia. Our previous studies have shown that the rates of glutamate/glutamine cycling and neuronal glucose oxidation change proportionally over a wide range of cortical activity. These observations place certain limits on the utilization of glucose by neurons and glia, and studies are underway to better define their contributions to brain energy metabolism in vivo. A major effort in our laboratory is focused on the utilization of the alternate (non-glucose) monocarboxylic acid substrates, lactate and ketone bodies. We are testing whether these alternate fuels can support brain energy and neurotransmitter metabolism during hypoglycemia, and whether adaptations to recurrent hypoglycemia, a model of type-1 diabetes, alters their capacity to be used as fuels. Our work involves strong collaborations with faculty members in the Departments of Diagnostic Radiology, Psychiatry, and Internal Medicine.

Selected Publications:

1. 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]
2. 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.
3. 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.
4. 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.
5. 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.
6. Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG, Behar KL. The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Proc Natl Acad Sci USA. 2005 Apr 12;102(15):5588-93. Epub 2005 Apr 4.
7. Patel AB, de Graaf RA, Mason GF, Kanamatsu T, Rothman DL, Shulman RG, Behar KL. Glutamatergic neurotransmission and neuronal glucose oxidation are coupled during intense neuronal activation. J Cereb Blood Flow Metab. 2004 Sep;24(9):972-85.
8. Shulman RG, Rothman DL, Behar KL, Hyder F. Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci. 2004 Aug;27(8):489-95. Review.
9. Sepkuty JP, Cohen AS, Eccles C, Rafiq A, Behar K, Ganel R, Coulter DA, Rothstein JD. A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy. J Neurosci. 2002 Aug 1;22(15):6372-9
10. Lebon V, Petersen KF, Cline GW, Shen J, Mason GF, Dufour S, Behar KL, Shulman GI, Rothman DL. Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci. 2002 Mar 1;22(5):1523-31.

For a further list of Behar's publications, please see PubMed.

Current and Former Trainees:

Postdoc trainees:

• David Manor, PhD
• Ikuhiro Kida, PhD
• Pavel Shkarin, PhD
• Anant Patel, PhD
• Golam Chowdhury, PhD
• Lihong Jiang, PhD