Graeme Mason, PhD
Research & Publications
Biography
News
Research Summary
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, 2H, and 13C magnetic resonance spectroscopy and mathematical modeling of metabolism and enzyme kinetics, and the effects of alcohol and other substances 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 by nuclear magnetic resonance and mass spectrometry. 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, which allows a user to simulate the flow of isotopic labels through metabolism and follow their distribution in various isotopomeric patterns. 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 metabolism in the brain and other systems. 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, alcoholism, and post-traumatic stress 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.
Coauthors
Research Interests
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
Mental Health; Metabolism; Modeling; Substance Use, Addiction
Selected Publications
- 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 G, Kibbey RG. Integrated, Step-Wise, Mass-Isotopomeric Flux Analysis of the TCA Cycle. Cell Metabolism 2015, 22:936-47.
- Glutamate metabolism in major depressive disorder.Abdallah CG, Jiang L, De Feyter HM, Fasula M, Krystal JH, Rothman DL, Mason GF, Sanacora G. Glutamate metabolism in major depressive disorder. The American Journal Of Psychiatry 2014, 171:1320-7.
- Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure.Wang J, Du H, Jiang L, Ma X, de Graaf RA, Behar KL, Mason GF. Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110:14444-9.
- Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia.Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL. Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. The Journal Of Clinical Investigation 2013, 123:1988-98.
- Intravenous ethanol infusion decreases human cortical γ-aminobutyric acid and N-acetylaspartate as measured with proton magnetic resonance spectroscopy at 4 tesla.Gomez R, Behar KL, Watzl J, Weinzimer SA, Gulanski B, Sanacora G, Koretski J, Guidone E, Jiang L, Petrakis IL, Pittman B, Krystal JH, Mason GF. Intravenous ethanol infusion decreases human cortical γ-aminobutyric acid and N-acetylaspartate as measured with proton magnetic resonance spectroscopy at 4 tesla. Biological Psychiatry 2012, 71:239-46.
- Evaluation of cerebral acetate transport and metabolic rates in the rat brain in vivo using 1H-[13C]-NMR.Patel AB, de Graaf RA, Rothman DL, Behar KL, Mason GF. Evaluation of cerebral acetate transport and metabolic rates in the rat brain in vivo using 1H-[13C]-NMR. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 2010, 30:1200-13.
- Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine.Wang J, Jiang L, Jiang Y, Ma X, Chowdhury GM, Mason GF. Regional metabolite levels and turnover in the awake rat brain under the influence of nicotine. Journal Of Neurochemistry 2010, 113:1447-58.
- Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy.Boumezbeur F, Mason GF, de Graaf RA, Behar KL, Cline GW, Shulman GI, Rothman DL, Petersen KF. Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 2010, 30:211-21.
- Measurements of the anaplerotic rate in the human cerebral cortex using 13C magnetic resonance spectroscopy and [1-13C] and [2-13C] glucose.Mason GF, Petersen KF, de Graaf RA, Shulman GI, Rothman DL. Measurements of the anaplerotic rate in the human cerebral cortex using 13C magnetic resonance spectroscopy and [1-13C] and [2-13C] glucose. Journal Of Neurochemistry 2007, 100:73-86.
- Increased brain monocarboxylic acid transport and utilization in type 1 diabetes.Mason GF, Petersen KF, Lebon V, Rothman DL, Shulman GI. Increased brain monocarboxylic acid transport and utilization in type 1 diabetes. Diabetes 2006, 55:929-34.
- Reproducibility measurement of glutathione, GABA, and glutamate: Towards in vivo neurochemical profiling of multiple sclerosis with MR spectroscopy at 7T.Prinsen H, de Graaf RA, Mason GF, Pelletier D, Juchem C. Reproducibility measurement of glutathione, GABA, and glutamate: Towards in vivo neurochemical profiling of multiple sclerosis with MR spectroscopy at 7T. Journal Of Magnetic Resonance Imaging : JMRI 2017, 45:187-198.
- The human brain produces fructose from glucose.Hwang JJ, Jiang L, Hamza M, Dai F, Belfort-DeAguiar R, Cline G, Rothman DL, Mason G, Sherwin RS. The human brain produces fructose from glucose. JCI Insight 2017, 2:e90508.
- Metabotropic Glutamate Receptor 5 and Glutamate Involvement in Major Depressive Disorder: A Multimodal Imaging Study.Abdallah CG, Hannestad J, Mason GF, Holmes SE, DellaGioia N, Sanacora G, Jiang L, Matuskey D, Satodiya R, Gasparini F, Lin X, Javitch J, Planeta B, Nabulsi N, Carson RE, Esterlis I. Metabotropic Glutamate Receptor 5 and Glutamate Involvement in Major Depressive Disorder: A Multimodal Imaging Study. Biological Psychiatry : Cognitive Neuroscience And Neuroimaging 2017, 2:449-456.
- Impaired neuronal and astroglial metabolic activity in chronic unpredictable mild stress model of depression: Reversal of behavioral and metabolic deficit with lanicemine.Mishra PK, Adusumilli M, Deolal P, Mason GF, Kumar A, Patel AB. Impaired neuronal and astroglial metabolic activity in chronic unpredictable mild stress model of depression: Reversal of behavioral and metabolic deficit with lanicemine. Neurochemistry International 2020, 137:104750.
- A novel biomarker of neuronal glutamate metabolism in non-human primate using localized 1H MRS: Development and effects of BNC375, an α7 nicotinic acetylcholine receptor positive allosteric modulator.Miller CO, Liza T. Gantert LT, Previs SF, Chen Y, Anderson KD, Thomas JM, Sanacora S, Uslaner JM, Rothman DL, Mason GF. Biol Psych: Cogn Neurosci Neuroimag (in press)
Clinical Trials
| Conditions | Study Title |
|---|---|
| Diseases of the Nervous System; Mental Health & Behavioral Research | Examination of Glutamate and mGluR5 in Psychiatric Disorders |
| Mental Health & Behavioral Research | Imaging mGluR5 and synaptic density in psychiatric disorders |
| Diabetes Mellitus - Type 1; Diabetes Mellitus - Type 2; Diseases of the Endocrine System | Restoring brain metabolism and function in older adult T1DM patients using an AP system |
| Diabetes Mellitus - Type 1; Diseases of the Endocrine System; Diseases of the Nervous System | Impact of Hypoglycemia on Brain Ketone and Neurotransmitter Metabolism in Type 1 DM |
| Mental Health & Behavioral Research | Effect of Sleep Deprivation on Brain Imaging and Function |
| Diseases of the Nervous System; Mental Health & Behavioral Research | Biomarkers of Clinical Subtype and Treatment Response in Obsessive-Compulsive Disorder |