Alcoholic Intoxication; Alcoholism; Amino Acids; Carbohydrates; Central Nervous System Diseases; Fatty Acids; Mathematical Computing; Substance Withdrawal Syndrome; Tobacco Use Disorder; Mood Disorders; Cocaine-Related Disorders; Alcohol-Induced Disorders, Nervous System; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Neuroimaging
Public Health Interests
Alcoholism/Alcohol; Depression; Metabolism; Modeling
Psychiatry: Center for Nicotine and Tobacco Use Research at Yale (CENTURY) | Center for the Translational Neuroscience of Alcoholism | Neurocognition, Neurocomputation, and Neurogenetics, Division of | Neuroscience Research Training Program (NRTP) | Obsessive Compulsive Disorder Research Clinic
Dr. Mason's research program is focused on the development and evaluation of quantitative hypotheses of brain energy utilization, neurotransmitter metabolism, and function, as well as their application to neuropsychiatric disorders. Dr. Mason's primary methodologies are 1H and 13C magnetic resonance spectroscopy and mathematical modeling of metabolism and enzyme kinetics, and the effects of nicotine and ethanol on GABA, glutamate, and energy metabolism form a primary research focus for his program.
MRS uses technology that is similar to that of standard MRI, but the results are measurements of chemicals instead of images. The chemical measurements are used to measure the effects of variability in function, disease, and pharmacology on the concentrations of brain glutamate, glutamine, GABA and other compounds that are important for brain activity.
Among the most unique capacities of this laboratory is the ability to use MRS to measure metabolic rates with the stable isotope 13C. It is possible to observe the synthesis of glutamate, glutamine, GABA, and other compounds in the intact brain, with collaborative studies to examine other systems. Measurements of the synthesis of these compounds provide an assessment of neurotransmission and energetics in the brain. To plan experiments and evaluate data, mathematical simulations of brain metabolism are used with a user-friendly package called CWave. As theories are developed, new experiments planned, and new data obtained, the models are constantly under revision and expansion.
The goals of the laboratory are to acquire the necessary data and create concrete mathematical expressions of the metabolic regulation of brain metabolism. Such expressions will help understand basic biochemical regulation, aid the development and evaluation of pharmacologic agents, and predict the effects of functional perturbations on the health and activity of the human brain.
Extensive Research Description
Dr. Mason's research integrates quantitative approaches to measure functional brain chemistry and the study of neuropsychiatric disorders. The primary methods used are 1H and 13C magnetic resonance spectroscopy, with some studies using mass spectrometry, as well as the mathematical assessment of metabolism. Current areas of research include alcohol effects, depression, manic-depressive disorder, alcoholism, panic disorder, premenstrual syndrome, and obsessive-compulsive disorder. His primary areas of interest are the effects of alcohol on the brain, and to that end, his research evaluates acute and chronic effects of alcohol on the brain, from the perspectives of neurotransmission, metabolism, adaptation, and vulnerability to dependence.
Integrated, step-wise, mass-isotopomeric flux analysis of the TCA Cycle.
Alves TC, Pongratz RL, Zhao X, Yarborough O, Sereda S, Shirihai O, Cline GW, Mason GF, Kibbey RG (2015) Integrated, step-wise, mass-isotopomeric flux analysis of the TCA Cycle. Cell Metab (in press)
Glutamate metabolism in major depressive disorder.
Abdallah CG, Jiang L, De Feyter HM, Fasula MK, Krystal JH, Rothman DL, Mason GF, Sanacora G (2014) Glutamate Metabolism in Major Depressive Disorder. Amer J Psychiatry 171:1320-1327
Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure.
Wang J, Du H, Jiang L, Ma X, de Graaf R, Behar K, Mason GF (2013) Oxidation and Effects of Ethanol in the Rat Brain after Chronic Ethanol Exposure. Proc Natl Acad Sci USA 110: 14444-14449
- Exposure to antecedent recurrent hypoglycemia increases lactate uptake under hypoglycemia, supporting TCA cycle activity and neuronal function. Jiang L, Herzog RI, Herman P, Ganganna B, Mason GF, Hyder F, Rothman D, Sherwin R, Behar KL (2013) J Clin Inv 123: 1605-1614
Intravenous ethanol infusion decreases human cortical GABA and NAA as measured with 1H-MRS at 4T
Gomez R, Behar KL, Watzl J, Weinzimer SA, Gulanski B, Sanacora G, Koretski J, Guidone E, Jiang L, Petrakis IL, Pittman B3, Krystal JH, Mason GF (2012) Intravenous ethanol infusion decreases human cortical GABA and NAA as measured with 1H-MRS at 4T. Biol
Evaluation of cerebral acetate transport and utilization rates in the anesthetized rat in vivo using 1H-[13C]NMR and [2-13C]acetate.
Patel AB, de Graaf RA, Rothman DL, Behar KL, Mason GF (2010) Evaluation of cerebral acetate transport and utilization rates in the anesthetized rat in vivo using 1H-[13C]NMR and [2-13C]acetate. J Cereb Blood Flow Metab 30: 1200-1213
Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine.
Wang J, Jiang L, Jiang F, Ma X, Chowdhury GMI, Mason G (2010) Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine. J Neurochem 113: 1447-1458
- Boumezbeur F, Mason GF, de Graaf RA, Behar KL, Cline GW, Shulman GI, Rothman DL, Petersen DL (2010) Alterations in brain mitochondrial metabolism associated with aging in humans. J Cereb Blood Flow Metab 30: 211-221
Measurements of the anaplerotic rate in the human cerebral cortex using 13C MRS and [1-13C] and [2-13C]glucose.
Mason GF, Petersen KF, de Graaf RA, Shulman GI, Rothman DL (2007) Measurements of the anaplerotic rate in the human cerebral cortex using 13C MRS and [1-13C] and [2-13C]glucose. J Neurochem 100: 73-86.
Increased Brain Monocarboxylic Acid Transport and Utilization in Type 1 Diabetes.
Mason GF, Petersen KF, Lebon V, Rothman DL, Shulman GI (2006) Increased Brain Monocarboxylic Acid Transport and Utilization in Type 1 Diabetes. Diabetes 55: 929-934.