Alcoholic Intoxication; Alcoholism; Amino Acids; Brain Mapping; Carbohydrates; Central Nervous System Diseases; Fatty Acids; 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
Public Health Interests
Alcoholism/Alcohol; Depression; Metabolism; Modeling; Smoking/Tobacco Control
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. Measurements of the synthesis of these compounds provide a direct evaluation of neurotransmission 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, as well as the mathematical assessment of metabolism. Current areas of research include depression, manic-depressive disorder, alcoholism, panic disorder, premenstrual syndrome, and post-partum depression. His primary areas of interest are the effects of alcohol and nicotine dependence on the brain, and to that end, my research programs evaluate acute and chronic effects of alcohol and nicotine on the brain, from the perspectives of neurotransmission, metabolism, adaptation, and vulnerability to dependence.Acute Effects of Ethanol on Human Neurochemistry
Impact of Acute Nicotine on Human Amino Acid Neurotransmission
Effects of Heavy Drinking on Brain Energy Metabolism
Cerebral Metabolism of Ethanol
- 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
- Jiang L, Herzog RI, Herman P, Ganganna B, Mason GF, Hyder F, Rothman D, Sherwin R, Behar KL (2013) Exposure to antecedent recurrent hypoglycemia increases lactate uptake under hypoglycemia, supporting TCA cycle activity and neuronal function. J Clin Inv 1
- 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
- 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
- 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
- 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.
- 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.