Effects of Chronic Alcohol Consumption on the Broad Phospholipid Signal in Human Brain: An In Vivo 31P MRS Study
M. R. Estilaei
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorG. B. Matson
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorG. S. Payne
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorM. O. Leach
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorG. Fein
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorCorresponding Author
D. J. Meyerhoff
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Reprint requests: Dieter J. Meyerhoff, Dr.rer.nat., Magnetic Resonance Unit (114M), Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121; Fax: 415-668-2864; E-mail: [email protected]Search for more papers by this authorM. R. Estilaei
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorG. B. Matson
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorG. S. Payne
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorM. O. Leach
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorG. Fein
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Search for more papers by this authorCorresponding Author
D. J. Meyerhoff
Department of Radiology (MRE, GBM, DJM), MR Unit DVA Medical Center, University of California San Francisco, California; CRC Clinical Magnetic Resonance Research Group (GSP, MOL), Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom; and Neurobehavioral Research Inc. (GF), San Rafael, California.
Reprint requests: Dieter J. Meyerhoff, Dr.rer.nat., Magnetic Resonance Unit (114M), Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121; Fax: 415-668-2864; E-mail: [email protected]Search for more papers by this authorSupported by PHS Grant AA10788 (DJM).
Abstract
Background: Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the measurement of phospholipids and their breakdown products in the human brain. Fairly mobile membrane phospholipids give rise to a broad signal that co-resonates with metabolic phosphodiesters. Chronic alcohol exposure increases the rigidity of isolated brain membranes and, thus, may affect the amount and transverse relaxation times (T2) of MRS-detectable phospholipids. We tested the hypothesis that subjects who were heavy drinkers have stiffer membranes than controls who were light drinkers, as reflected in a smaller broad signal component and a shorter T2 of the broad signal in 31P MR spectra of the brain.
Methods: Thirteen alcohol-dependent heavy drinkers (mean age 44 years) were studied by localized 31P MRS in the centrum semiovale and compared with 17 nondependent light drinkers of similar age. The broad component signal was separated from the metabolite signal by convolution difference, which is based on the large difference in line widths of these two signals. Longitudinal and T2 relaxation times were measured using standard methods.
Results: The broad component integral was 13% lower in the brain of heavy drinkers compared with light drinkers (p < 0.001) and remained significantly smaller after corrections for both longitudinal and transverse relaxations (p < 0.01). The T2 distribution of the broad component consistently showed two resolvable components in both groups. The fast relaxing component had the same T2 in both groups (T2= 1.9 msec). The slower relaxing component T2 was 0.6 msec shorter in heavy drinkers compared with light drinkers (p= 0.08).
Conclusions: These results, observed in the absence of white matter volume loss, are consistent with biochemical alterations and higher rigidity of white matter phospholipids associated with long-term chronic alcohol abuse. The observed smaller broad signal component in these relatively young heavy drinkers is a sensitive measure of white matter phospholipid damage.
REFERENCES
- Alling C, Liljequist S, Engel J (1982) The effect of chronic ethanol administration on lipids and fatty acids in subcellular fractions of rat brain. Med Biol 60: 149–154.
- Altura BM, Altura BT, Gupta RK (1992) Alcohol intoxication results in rapid loss in free magnesium in brain and disturbances in brain bioenergetics: Relation to cerebrovasospasm, alcohol-induced strokes, and barbiturate anesthesia-induced deaths. Magnes Trace Elem 10: 122–135.
- Bárány M, Chang YC, Arús C, Rustan T, Frey WH (1985) Increased glycerol-3-phosphorylcholine in post-mortem Alzheimer's brain [letter]. Lancet 1: 517.
- Beaugé F, Stibler H, Borg S (1985) Abnormal fluidity and surface carbohydrate contents of erythrocyte membrane in alcoholic patients. Alcohol Clin Exp Res 9: 322.
- Cerdan S, Subramanian VH, Hilberman M, Cone J, Egan J, Chance B, Williamson JR (1986) 31P NMR detection of mobile dog brain phospholipids. Magn Reson Med 3: 432–439.
- Chin JH, Goldstein DB (1977) Drug tolerance in biomembranes: A spin label study of the effects of ethanol. Science 196: 684–685.
- Christensen JD, Kaufman MJ, Levin JM, Mendelson JH, Holman BL, Cohen BM, Renshaw PF (1996) Abnormal cerebral metabolism in polydrug abusers during early withdrawal: A 31P MR spectroscopy study. Magn Reson Med 35: 658–663.
- Crews FT, Majchrowicz E, Meeks R (1983) Changes in cortical synaptosomal plasma membrane fluidity and composition in ethanol-dependent rats. Psychopharmacology 81: 208–213.
- Deitrich RA, Dunwiddie TV, Harris AR, Erwin VG (1989) Mechanism of action of ethanol: Initial CNS actions. Pharmacol Rev 41: 489–537.
- Denays R, Chao SL, Mathur-Devre R, Jeghers O, Fruhling J, Noel P, Ham HR (1993) Metabolic changes in the rat brain after acute and chronic ethanol intoxication: A 31P NMR spectroscopy study. Magn Reson Med 29: 719–723.
- Doyle K, Hojnacki J, Cluette-Brown J (1990) Ethanol-induced alterations in erythrocyte membrane phospholipid composition. Am J Med Sci 299: 98–102.
- Estilaei MR, Matson G, Fein G, Meyerhoff DJ (2000a) Effects of chronic alcohol use on the broad phospholipid component in brain using 31P MRSI, In Proceedings of the International Society of Magnetic Resonance in Medicine (ISMRM), p 1164.
- Estilaei MR, Matson G, Fein G, Meyerhoff DJ (2000b) Effects of abstinence from alcohol on the broad phospholipid signal in 31P ISIS spectra. In Proceedings of the ISMRM, p 1163.
- Foudin L, Sun GY, Sun AY (1986) Changes in lipid composition of rat heart mitochondria after chronic ethanol administration. Alcohol Clin Exp Res 10: 606–609.
- Goldman H, Tolous-Shams G, Fein G, Meyerhoff DJ (1999) Dose-related frontal gray matter loss in active young drinkers: A quantitative MRI study. Alcohol Clin Exp Res 23: 67A.
- Gustavsson L, Alling C (1989) Effects of chronic ethanol exposure on fatty acids of rat brain glycerophospholipids. Alcohol Alcohol 6: 139–146.
- Harris RA, Baxter DM, Mitchell MA, Hitzemann RJ (1984a) Physical properties and lipid composition of brain membranes from ethanol tolerant-dependent mice. Mol Pharmacol 25: 401–409.
- Harris RA, Crabbe JC, McSwigan JD (1984b) Relationship of membrane physical properties to alcohol dependence in mice selected for genetic differences in alcohol withdrawal. Life Sci 35: 2601–2608.
- Harris RA, Groh GI, Baxter DM, Hitzemann RJ (1984c) Gangliosides enhance the membrane actions of ethanol and pentobarbital. Mol Pharmacol 25: 410–417.
- Husted CA, Matson GB, Adams DA, Goodkin DS, Weiner MW (1994) In vivo detection of myelin phospholipids in multiple sclerosis with phosphorus magnetic resonance spectroscopic imaging. Ann Neurol 36: 239–241.
- Kalant H (1971) Absorption, diffusion, distribution, and elimination of ethanol: Effects on biological membranes, in The Biology of Alcoholism ( B Kissin, H Begleiter, eds. pp 1–62. Plenum Press: New York .
- Kanashiro M, Naritomi H, Sasaki M, Tsuji S, Miyake Y (1990) Non-invasive 31P NMR study on the development of brain membrane of gerbils and jimpy mice, a myelin-deficient mutant. Physiol Chem Phys Med NMR 22: 141–154.
- Kilby PM, Allis JL, Radda GK (1990) Spin-spin relaxation of the phosphodiester resonance in the 31P NMR spectrum of human brain. The determination of the concentrations of phosphodiester components. FEBS Lett 272: 163–165.
- Kilby PM, Bolas NM, Radda GK (1991) 31P-NMR study of brain phospholipid structures in vivo. Biochim Biophys Acta 1085: 257–264.
- Kril JJ, Halliday GM, Svoboda MD, Cartwright H (1997) The cerebral cortex is damaged in chronic alcoholics. Neuroscience 79: 983–998.
- Kwee IL, Nakada T (1988) Phospholipid profile of the human brain: 31P NMR spectroscopic study. Magn Reson Med 6: 296–299.
- Littleton JM, John G (1977) Synaptosomal membrane lipids of mice during continuous exposure to ethanol. Pharm Pharmac 29: 579–580.
- Lyon RC, Goldstein DB (1983) Changes in synaptic membrane order associated with chronic ethanol treatment in mice. Mol Pharmacol 23: 86–91.
- MacKay S, Meyerhoff DJ, Dillon WP, Weiner MW, Fein G (1993) Alteration of brain phospholipid metabolites in cocaine-dependent polysubstance abusers. Biol Psychiatry 34: 261–264.
- MacKay S, Ezekiel F, Di Sciafani V, Meyerhoff DJ, Gerson J, Norman D, Fein G, Weiner MW (1996) Alzheimer disease and subcortical ischemic vascular dementia: Evaluation by combining MR imaging segmentation and H-1 MR spectroscopic imaging. Radiology 198: 537–545.
-
Matson GB,
Vermathen P,
Hill TC (1999) A practical double-tuned 1H/31P quadrature birdcage headcoil optimized for 31P operation.
Magn Reson Med
42: 173–182.
10.1002/(SICI)1522-2594(199907)42:1<173::AID-MRM23>3.0.CO;2-O CAS PubMed Web of Science® Google Scholar
- McNamara R, Arias-Mendoza F, Brown TR (1994) Investigation of broad resonances in 31P NMR spectra of the human brain in vivo. NMR Biomed 7: 237–242.
- Meyerhoff DJ, MacKay S, Sappey-Marinier D, Deicken R, Calabrese G, Dillon WP, Weiner MW, Fein G (1995) Effects of chronic alcohol abuse and HIV infection on brain phosphorus metabolites. Alcohol Clin Exp Res 19: 685–692.
- Murphy EJ, Rajagopalan B, Brindle KM, Radda GK (1989) Phospholipid bilayer contribution to 31P NMR spectra in vivo. Magn Reson Med 12: 282–289.
- Ordidge RJ, Connelly A, Lohman JAB (1986) Image-selected in vivo spectroscopy (ISIS). A new technique for spatially selective NMR spectroscopy. J Magn Reson 66: 283–294.
- Petroff OA, Novotny EJ, Ogino T, Avison M, Prichard JW (1990) In vivo measurements of ethanol concentration in rabbit brain by 1H magnetic resonance spectroscopy. J Neurochem 54: 1188–1195.
- Pfefferbaum A, Sullivan EV, Mathalon DH, Shear PK, Rosenbloom MJ, Lim KO (1995) Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics. Alcohol Clin Exp Res 19: 1177–1191.
- Rajan S, Kang SY, Gutowsky HS, Oldfield E (1981) Phosphorus nuclear magnetic resonance study of membrane structure. Interactions of lipids with protein, polypeptide, and cholesterol. J Biol Chem 256: 1160–1166.
- Rawat AK (1974) Lipid metabolism in brains from mice chronically fed ethanol. Res Commun Chem Pathol Pharmacol 8: 461–469.
- Roth K, Kimber BJ (1982) Determination of optimal parameters in the convolution difference resolution enhancement technique. Org Magn Reson 18: 197–198.
- Rottenberg H, Waring A, Rubin E (1981) Tolerance and cross-tolerance in chronic alcoholics: Reduced membrane binding of ethanol and other drugs. Science 213: 583–585.
- Rowe ES (1992) Effects of ethanol on membrane lipids, in Alcohol and Neurobiology: Receptors, Membranes and Channels RR Watson, ed pp. 239–267. CRC Press, New York .
- Sauter R, Mueller S, Weber H (1987) Localization in in vivo 31P NMR spectroscopy by combining surface coils and slice-selective saturation. J Magn Reson 75: 167–173.
- Shear PK, Jernigan TL, Butters N (1994) Volumetric magnetic resonance imaging quantification of longitudinal brain changes in abstinent alcoholics [published erratum appears in Alcohol Clin Exp Res 18: 766]. Alcohol Clin Exp Res 18: 172–176.
-
Stanisz GJ,
Kecojevic A,
Bronskill MJ,
Henkelman RM (1999) Characterizing white matter with magnetization transfer and T(2).
Magn Reson Med
42: 1128–1136.
10.1002/(SICI)1522-2594(199912)42:6<1128::AID-MRM18>3.0.CO;2-9 CAS PubMed Web of Science® Google Scholar
- Sun GY, Sun AY (1979) Effect of chronic ethanol administration on phospholipid acyl groups of synaptic plasma membrane fraction isolated from guinea pig brain. Res Commun Chem Pathol Pharmacol 24: 405–408.
- Sun GY, Sun AY (1983) Chronic ethanol administration induced an increase in phosphatidylserine in guinea pig synaptic plasma membranes. Biochem Biophys Res Commun 113: 262–268.
- Tan CYK, Weaver DF (1997) Molecular pathogenesis of alcohol withdrawal seizures: Modified lipid-protein interaction mechanism. Seizure 6: 255–274.
- Tanabe JL, Amend D, Schuff N, Di Sclafani V, Ezekiel F, Norman D, Fein G, Weiner MW (1997) Tissue segmentation of the brain in Alzheimer's disease. Am J Neurorad 18: 115–123.
- Vrbaski SR, Grujiâc-Injac B, Ristiâc M (1984) Phospholipid and ganglioside composition in rat brain after chronic intake of ethanol. J Neurochem 42: 1235–1239.
- Wood WG, Rao AM, Igbavboa U, Semotuk M (1993) Cholesterol exchange and lateral cholesterol pools in synaptosomal membranes of pair-fed control and chronic ethanol-treated mice. Alcohol Clin Exp Res 17: 345–350.
