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Homocysteine and alcoholism

  • Conference paper
Advances in Research on Neurodegeneration

Summary

Chronic alcohol consumption can induce alterations in the function and morphology of most if not all brain systems and structures. However, the exact mechanism of brain damage in alcoholics remains unknown. Partial recovery of brain function with abstinence suggests that a proportion of the deficits must be functional in origin (i.e. plastic changes of nerve cells) while neuronal loss from selected brain regions indicates permanent and irreversible damage. There is rowing evidence that chronic alcoholism is associated with a derangement in the sulfur amino acid metabolism. Recently, it has been shown that excitatory amino acid (EAA) neurotransmitters and homocysteine levels are elevated in patients who underwent withdrawal from alcohol. Furthermore, it has been found that homocysteine induces neuronal cell damage by timulating NMDA receptors as well as by producing free radicals. Homocysteine neurotoxicity via overstimulation of N- ethyl-D-aspartate receptors may contribute to the pathogenesis of both brain shrinkage and withdrawal seizures linked to alcoholism.

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References

  • Barak AJ, Beckenhauer HC, Tuma DJ (1991) Hepatic transmethylation and blood alcohol levels. Alcohol Alcohol 26: 125–128

    PubMed  CAS  Google Scholar 

  • Barak AJ, Beckenhauer HC, Tuma DJ (1996) Betaine, ethanol, and the liver: a review. Alcohol 13: 395–398

    Article  PubMed  CAS  Google Scholar 

  • Beal MF (1992) Mechanisms of excitotoxicity in neurologic diseases. FASEB J 6: 33383344

    Google Scholar 

  • Bleich S, Degner D (2000) Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine: a study in rats. Alcohol Alcohol 35: 215

    PubMed  CAS  Google Scholar 

  • Bleich S, Degner D, Kornhuber J (2000a) Repeated ethanol withdrawal delays development of focal seizures in hippocampal kindling. Alcohol Clin Exp Res 24: 244–245

    Article  CAS  Google Scholar 

  • Bleich S, Degner D, Wiltfang J, Maler JM, Niedmann P, Cohrs S, Mangholz A, Porzig J, Sprung R, Rüther E, Kornhuber J (2000b) Elevated homocysteine levels in alcohol withdrawal. Alcohol Alcohol 35: 351–354

    CAS  Google Scholar 

  • Bleich S, Degner D, Javaheripour K, Havemann-Reinecke U, Wiltfang J, Maler JM, Hellenbrand U, Rüther E, Kornhuber J (2000c) Brain shrinkage in alcoholism. Do an altered methionine metabolism and oxidative stress play a pathogenetic role? Neurosci Lett (submitted)

    Google Scholar 

  • Bleich S, Degner D, Kropp S, Rüther E, Kornhuber J (2000d) Red wine, spirits, beer and serum homocysteine. Lancet 356: 9228

    Google Scholar 

  • Bora PS, Lange LG (1993) Molecular mechanism of ethanol metabolism by human brain to fatty acid ethyl esters. Alcohol Clin Exp Res 17: 28–30

    Article  PubMed  CAS  Google Scholar 

  • Chandler LJ, Newsom H, Sumners C, Crews FT (1993) Chronic ethanol exposure potentiates NMDA excitotoxicity in cerebral cortical neurons. J Neurochem 60: 1578–1581

    Article  PubMed  CAS  Google Scholar 

  • Cuenod M, Do KQ, Grandes P, Morino P, Streit P (1990) Localization and release of homocysteic acid, an excitatory sulfur-containing amino acid. J Histochem Cytochem 38: 1713–1715

    Article  PubMed  CAS  Google Scholar 

  • Curtis D, Sparrow R, Brennan L, van der Weyden MB (1994) Elevated serum homocys-teine as a predictor for vitamin B12 or folate deficiency. Eur J Haematol 52: 227–232

    Article  PubMed  CAS  Google Scholar 

  • Di Sclafani V, Ezekiel F, Meyerhoff DJ, MacKay S, Dillon WP, Weiner MW, Fein G (1995) Brain atrophy and cognitive function in older abstinent alcoholic men. Alcohol Clin Exp Res 19: 1121–1126

    Article  PubMed  CAS  Google Scholar 

  • Fadda F, Rossetti ZL (1998) Chronic ethanol consumption: From neuroadaption to neurodegeneration. Prog Neurobiol 56: 385–431

    Article  PubMed  CAS  Google Scholar 

  • Finkelstein JD (1990) Methionine metabolism in mammals. J Nutr Biochem 1: 228–237 Grant KA, Valverius P, Hudspith M, Tabakoff B (1990) Ethanol withdrawal seizures and the NMDA receptor complex. Eur J Pharmacol 176: 228–237

    Google Scholar 

  • Halsted CH, Keen CL (1990) Alcoholism and micronutrient metabolism and deficiencies. Eur J Gastroenterol Hepatol 2: 399–405

    Google Scholar 

  • Halsted CH, Robles EA, Mezey E (1971) Decreased jejunal uptake of labeled folic acid (3H-PGA) in alcoholic patients: roles of alcohol and nutrition. N Eng J Med 285: 701706

    Google Scholar 

  • Harper C (1998) The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain? J Neuropathol Exp Neurol 57: 101–110

    Article  PubMed  CAS  Google Scholar 

  • Hoffman PL, Rabe CS, Grant KA, Valverius P, Hudspith M, Tabakoff B (1990) Ethanol and the NMDA receptor. Alcohol 7: 229–231

    Article  PubMed  CAS  Google Scholar 

  • Hultberg B, Berglund M, Andersson A, Frank A (1993) Elevated plasma homocysteine in alcoholics. Alcohol Clin Exp Res 17: 687–689

    Article  PubMed  CAS  Google Scholar 

  • Kang SS (1995) Critical points for determining moderate hyperhomocyst(e)inaemia. Eur J Clin Invest 25: 806–808

    Article  PubMed  CAS  Google Scholar 

  • Kang SS, Wong PWK (1996) Genetic and nongenetic factors for moderate hyperhomocyst(e)inemia. Atherosclerosis 119: 135–138

    Article  PubMed  CAS  Google Scholar 

  • Kang SS, Wong PWK, Norusis M (1987) Homocysteinemia due to folate deficiency. Metabolism 36: 458–462

    Article  PubMed  CAS  Google Scholar 

  • Kenyon SH, Nicolaou A, Gibbons WA (1998) The effect of ethanol and its metabolites upon methionine synthase activity in vitro. Alcohol 15: 305–309

    Article  PubMed  CAS  Google Scholar 

  • Kim W-K, Pae Y-S (1996) Involvement of N-methyl-D-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture. Neurosci Lett 216: 117–120

    PubMed  CAS  Google Scholar 

  • Kornhuber J, Bleich S (1999) Memantin. In: Riederer P, Laux G, Pöldinger W (eds). Neuro-Psychopharmaka, 2. edn, vol 5. Springer Wien New York, 685–704

    Google Scholar 

  • Kornhuber J, Weller M, Schoppmeyer K, Riederer P (1994) Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. J Neural Transm Suppl 43: 91–104

    PubMed  CAS  Google Scholar 

  • Kril JJ, Halliday GM (1999) Brain shrinkage in alcoholics: a decade on and what have we learned? Prog Neurobiol 58: 381–387

    Article  PubMed  CAS  Google Scholar 

  • Lieber CS (1988) Biochemical and molecular basis of alcohol-induced injury to liver and other tissues. N Eng J Med 319: 1639–1650

    Article  CAS  Google Scholar 

  • Lipton SA, Rosenberg PA (1994) Mechanisms of disease: Excitatory amino acids as a final common pathway for neurologic disorders. N Eng J Med 330: 613622

    Google Scholar 

  • Lipton SA, Kim WK, Choi YB, Kumar S, Dèmilia DM, Rayudu PV, Arnelle DR, Stamler JS (1997) Neurotoxicity associated with dual actions of homocysteine at the Nmethyl-D-aspartate receptor. Proc Natl Acad Sci USA 94: 5923–5928

    Article  PubMed  CAS  Google Scholar 

  • Lustig HS, Chan J, Greenberg DA (1992) Ethanol inhibits excitotoxicity in cerebral cortical cultures. Neurosci Lett 135: 259–261

    Article  PubMed  CAS  Google Scholar 

  • Mares P, Folbergrova J, Langmeier M, Haugvicova R, Kubova H (1997) Convulsant action of D,L-homocysteic acid and its stereoisomers in immature rats. Epilepsia 38: 767–776

    Article  PubMed  CAS  Google Scholar 

  • McCully KS (1993) Chemical pathology of homocysteine. I Atherogenesis. Ann Clin Lab Sci 23: 477–493

    PubMed  CAS  Google Scholar 

  • Outinen PA, Sood SK, Liaw PCY, Sarge KD, Maeda N, Hirsh J, Ribau J, Podor TJ, Weitz JI, Austin RC (1998) Characterization of the stress-inducing effects of homocysteine. Biochem J 332: 213–221

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Quinn CT, Griener JC, Bottiglieri T, Hyland K, Farrow A, Kamen BA (1997) Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF of children who receive methotrexate for the treatment of cancer. J Clin Oncol 15: 2800–2806

    PubMed  CAS  Google Scholar 

  • Refsum H, Ueland PM, Nygârd O, Vollset SE (1998) Homocysteine and cardiovascular disease. Ann Rev Med 49: 31–62

    Article  PubMed  CAS  Google Scholar 

  • Spanagel R, Kornhuber J (1999) Glutamate receptor agonists and alcohol dependence. Nervenarzt 70: 479–481

    Article  PubMed  CAS  Google Scholar 

  • Sullivan LW, Herbert V (1964) Suppression of hematopoiesis by ethanol. J Clin Invest 43: 2048–2061

    Article  PubMed  CAS  Google Scholar 

  • Thompson GA, Kilpatrick IC (1996) The neurotransmitter candidature of sulphur-containing excitatory amino acids in the mammalian central nervous system. Pharmacol Ther 72: 25–36

    Article  PubMed  CAS  Google Scholar 

  • Tsai GE, Ragan P, Chang R, Chen S, Linnoila VM, Coyle JT (1998) Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawal. Am J Psychiatry 155: 726–732

    PubMed  CAS  Google Scholar 

  • Authors’ address: Dr. Stefan Bleich, MD, Georg-August-University, Department of Psychiatry, Von-Siebold-Strasse 5, D-37075 Göttingen, Germany. Email: stefan.bleich@t-online.de

    Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Georg-August-University of Göttingen, Göttingen, Federal Republic of Germany

    S. Bleich, D. Degner, C. Kurth & J. Kornhuber

  2. Department of Neuroradiology, Georg-August-University of Göttingen, Göttingen, Federal Republic of Germany

    K. Javaheripour

Authors
  1. S. Bleich
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  2. D. Degner
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  3. K. Javaheripour
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  4. C. Kurth
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  5. J. Kornhuber
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Editor information

Editors and Affiliations

  1. Department of Psychiatry, University of Würzburg, Federal Republic of Germany

    P. Riederer

  2. Neurodegenerative Disorders Centre, Faculty of Medicine, University Hospital, Vancouver, B.C., Canada

    D. B. Calne

  3. Schering AG Berlin, Berlin, Federal Republic of Germany

    R. Horowski

  4. Department of Neurology, Juntendo University, Tokyo, Japan

    Y. Mizuno

  5. Department of Neurology, Mount Sinai Medical Center, New York, New York, USA

    C. W. Olanow

  6. Department of Neurology, University of Innsbruck, Innsbruck, Austria

    W. Poewe

  7. Department of Pharmacology, Faculty of Medicine, Technion, Haifa, Israel

    M. B. H. Youdim

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© 2000 Springer-Verlag Wien

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Bleich, S., Degner, D., Javaheripour, K., Kurth, C., Kornhuber, J. (2000). Homocysteine and alcoholism. In: Riederer, P., et al. Advances in Research on Neurodegeneration. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6301-6_12

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  • DOI: https://doi.org/10.1007/978-3-7091-6301-6_12

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83537-1

  • Online ISBN: 978-3-7091-6301-6

  • eBook Packages: Springer Book Archive

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