Skip to main content
SpringerLink
Log in

Alcohol, Neuron Apoptosis, and Oxidative Stress

  • Chapter
  • First Online:
Book cover Metabolic Encephalopathy

  • 1038 Accesses

Abstract

The aim of this chapter is to present a contemporary overview of ethanol-induced apoptosis in the brain, with a focus on the potential role of oxidative stress and some new concepts related to glia-mediated neuroprotection and selective vulnerability of neurons to ethanol. While ethanol-related oxidative stress and neuron apoptotic death have been documented in the adult brain, the vast majority of reports have centered on the developing organ (Schenker et al., 1990). We address both settings and offer several potential explanations for the high sensitivity of the fetal brain to these toxic responses to ethanol. Of note is that neurotoxic responses to ethanol have been recognized for several decades yet the mechanisms underlying these often devastating effects remain controversial. The following material abundantly illustrates that the setting is multifactorial with multiple ethanol-related perturbations at play, likely with each impacting to different degrees on various brain areas as well as on different neuron and glia populations. Finally, neuron survival and functions are intimately connected to the glia with which neurons are commingled. Such interactions may often be essential to neuron survival and we include a brief overview of recent studies addressing ethanol effects on neuroprotective glia/neuron interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bailey, S.M. and Cunningham, C.C. (2002). Contribution of mitochondria to oxidative stress associated with alcoholic liver disease. Free Rad. Biol. Med. 32:11–16.

    Article  CAS  PubMed  Google Scholar 

  • Bao, Q. and Shi, Y. (2007). Apoptosome: a platform for the activation of initiator caspases. Cell Death Diff. 14:56–65.

    Article  CAS  Google Scholar 

  • Bignami, A. (1991). Glial cells in the central nervous system. In: Magistretti, P.J. (ed.), Discussions in Neuroscience, vol. 8, Elsevier, Amsterdam, pp. 1–45.

    Google Scholar 

  • Boveris, A., Llesuy, S., Azzalis, L.A., Giavarotti, L., Simon, K.A., Junqueira, V.B., Porta, E.Z., Vivelda, E.A., and Lissi, E.A. (1997). In situ rat brain and liver spontaneous chemiluminescence after acute ethanol intake. Toxicol. Lett. 93:23–28.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese, V., Scapagnini, G., Latteri, S., Colombrita, C., Ravagna, A., Catalano, C., Pennisi, G., Calvani, M., and Butterfield, D.A. (2002). Long-term ethanol administration enhances age-dependent modulation of redox state in different brain regions in the rat: protection by acetyl carnitine. Int. J. Tissue React. 24:97–104.

    CAS  PubMed  Google Scholar 

  • Carloni, S., Mazzoni, E., and Balduini, W. (2004). Caspase-3 and calpain activities after acute and repeated ethanol administration during the rat brain growth spurt. J. Neurochem. 89:197–203.

    Article  CAS  PubMed  Google Scholar 

  • Cederbaum, A.I. (1989). Introduction: role of lipid peroxidation and oxidative stress in alcohol toxicity. Free Rad. Biol. Med. 7:537–539.

    Article  CAS  PubMed  Google Scholar 

  • Chen, J., Peterson, D., Schenker, S., and Henderson, G.I. (2000). Formation of malondialdehyde adducts in livers of rats exposed to ethanol: Role in ethanol-mediated inhibition of cytochrome c oxidase. Alcoholism: Clin. Exp. Res. 24(4):544–552.

    Article  CAS  Google Scholar 

  • Chen, J.J., Robinson, N.C., Schenker, S., Frosto, T.A., and Henderson, G.I. (1999). Formation of 4-hydroxynonenal adducts with cytochrome c oxidase in rats following short-term ethanol intake. Hepatology 26:1792–1798.

    Article  Google Scholar 

  • Climent, E., Pascual, M., Renau-Piqueras, J., and Guerri, C. (2002). Ethanol exposure enhances cell death in the developing cerebral cortex: role of brain-derived neurotrophic factor and its signaling pathways. J. Neurosci. Res. 68:213–225.

    Article  CAS  PubMed  Google Scholar 

  • Cooper, A.J.L. (1997). Glutathione in the brain: disorders of glutathione metabolism. In: (Rosenberg, R.N., Prusiner, S.B., DiMauro, S., Barchi, R.L. and Kunk, L.M., eds). The Molecular and Genetic Basis of Neurological Disease, Butterworth-Heinemann, Boston, pp. 1195–1230.

    Google Scholar 

  • Curtin, J.F., Donovan, M., and Cotter, T.G. (2002). Regulation and measurement of oxidative stress in apoptosis. J. Immunol. Metab. 265:49–72.

    Article  CAS  Google Scholar 

  • Dawson, T.L., Gores, G.J., Nieminen, A.L., Herman, B., and Lemasters, J.J. (1993). Mitochondria as a source of reactive oxygen species during reductive stress in rat hepatocytes. Am. J. Physiol. 264:C961–C967.

    CAS  PubMed  Google Scholar 

  • de la Monte, S.M. and Wands, J.R. (2001). Mitochondrial DNA damage and impaired mitochondrial function contribute to apoptosis of insulin-stimulated ethanol-exposed neuronal cells. Alcohoism: Clin. Exp. Res. 25:898–906.

    Article  CAS  Google Scholar 

  • de la Monte, S.M. and Wands, J.R. (2002). Chronic gestational exposure to ethanol impairs insulin-stimulated survival and mitochondrial function in cerebellar neurons. Cell Mol. Life Sci. 59:882–893.

    Article  CAS  PubMed  Google Scholar 

  • DeLeve, L. and Kaplowitz, N. (1990). Importance and regulation of hepatic GSH. Semin. Liver Dis. 10:251–266.

    Article  CAS  PubMed  Google Scholar 

  • Delivani, P. and Martin, S.J. (2006). Mitochondrial membrane remodeling in apoptosis: and inside story. Cell Death Diff. 13:2007–2010.

    Article  CAS  Google Scholar 

  • Del Maestro, R. and McDonald, W. (1989). Subcellular localization of superoxide dismutases, glutathione peroxidase and catalase in developing rat cerebral cortex. Mech. Age Dev. 48:15–21.

    Article  CAS  Google Scholar 

  • Del Maestro, R. and McDonald, W. (1989). Subcellular localization of superoxide dismutases, glutathione peroxidase and catalase in developing rat cerebral cortex. Mech. Age Dev. 48:15–21.

    Article  CAS  Google Scholar 

  • Dembele, K., Yao, X.H., Chen, L., and Nyomba, B.L.G. (2006). Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291:R796–R802.

    Article  CAS  PubMed  Google Scholar 

  • Devi, B.G., Henderson, G.I., Frosto, T.A., and Schenker, S. (1993). Effect of ethanol on rat fetal hepatocytes: studies on cell replication, lipid peroxidation and glutathione. Hepatology 18:648–659.

    Article  CAS  PubMed  Google Scholar 

  • Devi, B.G., Henderson, G.I., Frosto, T.A., and Schenker, S. (1994). Effects of acute ethanol exposure on cultured fetal rat hepatocytes: Relation to mitochondrial functions. Alcoholism: Clin. Exp. Res. 18:1436–1442.

    Article  CAS  Google Scholar 

  • Devi, B.G., Schenker, S., Mazloum, B., and Henderson, G.I. (1996). Ethanol-induced oxidative stress and enzymatic defenses in cultured fetal rat hepatocytes. Alcohol. 13:1–6.

    Article  Google Scholar 

  • Di Luzio, N.R. (1963). Prevention of acute ethanol-induced fatty liver by antioxidants. Physiologist. 6:169–173.

    Google Scholar 

  • Dreosti, I.E. (1987). Micronutrients, superoxide and the fetus. Neuro. Toxicol. 8:445–450.

    CAS  Google Scholar 

  • Dreosti, I.E., and Partick, E.J. (1987). Zinc, ethanol, and lipid peroxidation in adult and fetal rats. Biol. Trace Element Res. 14:179–191.

    Article  CAS  Google Scholar 

  • Dringen, R., Gutterer, J.M., Gros, G., and Hirrlinger, J. (2001). Aminopeptidase N mediates the utilization of the GSH precursor CysGly by cultured neurons. J. NeuroSci. Res. 66:1003–1008.

    Article  CAS  PubMed  Google Scholar 

  • Dringen, R., Kranich, O., and Hamprecht, B. (1997). The γ-glutamyl transpeptidase inhibitor acivicin preserves glutathione released by astroglial cells in culture. Neurochem. Res. 22:727–733.

    Article  CAS  PubMed  Google Scholar 

  • Dringen, R., Kussmaul, L., Gutterer, J., Hirrlinger, J., and Hamprecht, B. (1999). The glutathione system of peroxide detoxification is less efficient in neurons than in astroglial cells. J. Neurochem. 72:2523–2530.

    Article  CAS  PubMed  Google Scholar 

  • Drukarch, B., Schepens, E., Stoof, J., Langeveld, C.H., and Van Muiswinkel, F.L. (1989). Astrocyte-enhanced neuronal survival is mediated by scavenging of extracellular reactive oxygen species. Free Rad. Biol. Med. 25:217–220.

    Article  Google Scholar 

  • Druse, M.J., Tajuddin, N.F., Gillespie, R.A., and Le, P. (2006). The effects of ethanol and the serotonin (1A) agonist ipsapirone on the expression of the serotonin (1A) receptor and several antiapoptotic proteins in fetal rhombencephalic neurons. Brain Res. 1092:79–86.

    Article  CAS  PubMed  Google Scholar 

  • Dwivedi, S., Sharma, A., Patrick, B., Sharma, R., Awasthi, Y.C. (2007). Role of 4-hydroxynonenal and its metabolites in signaling. Redox Report 12(1):4–10.

    Article  PubMed  CAS  Google Scholar 

  • Ellis, H.M. and Horvitz, H.R. (1986). Genetic control of programmed cell death in the nematode C. elegans. Cell 44:817–829.

    Article  CAS  Google Scholar 

  • Esterbauer, H., Zollner, H., and Schaur, R.J. (1990). Aldehydes formed by lipid peroxidation: mechanisms of formation, occurrence, and determination. In: (Virgo-Peifrey, C., ed) Membrane Lipid Oxidation, CRC Press, Boca Raton, FL, pp 239–268.

    Google Scholar 

  • Falkowsky, P.G. (2006). Tracing oxygen’s imprint on earth metabolic evolution. Science 311:1724–1725.

    Article  Google Scholar 

  • Fleury, C., Mignotte, B., and Vayssiere, J.L. (2002). Mitochondrial reactive oxygen species in cell death signaling. Biochemie 84:131–141.

    Article  CAS  Google Scholar 

  • Garcia-Ruiz, C., Colell, A., Morales, A., Kaplowitz, N., and Fernandez-Checa, J.C. (1995). Role of oxidative stress generated from mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-nfk B: studies with isolated mitochondria and rat hepatocytes. Mol. Pharmacol. 48:825–834.

    CAS  PubMed  Google Scholar 

  • Garrido, C., Galluzzi, L., Brunet, M., Puig, P.E., Didelot, C. and Kroemer, G. (2007). Mechanisms of cytochrome c release from mitochondria. Cell Death Differ. 13:1423–1433.

    Article  CAS  Google Scholar 

  • Gegg, M.E., Beltran, B., Salas-Pino, S., Bolanos, J.P., Clark, J.B., Moncada, S. and Heales, S.J.R. (2003). Differential effect of nitric oxide on glutathione metabolism and mitochondrial function in astrocytes and neurons: implications for neuroprotection/ neurodegeneration?. J. Neurochem. 186:228–237.

    Google Scholar 

  • Gross, A., McDonnell, J.M., and Korsmyer, J. (1999). BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911.

    Article  CAS  PubMed  Google Scholar 

  • Hakem, R., Hakem, A., Duncam, G.S., Henderson, J.T., Woo, M., Soengas, M.S., Elia, A., de la Pompa, J.L., Kagi, D., Khoo, W., Potter, J., Yoshida, R., Kaufman, S.A., Lowe, S.W., Penninger, J.M., and Mak, T.W. (1998). Differental requirement for caspase-9 in apoptotic pathways in vivo. Cell 94:339–352.

    Article  CAS  PubMed  Google Scholar 

  • Halliwell, B. and Gutteridge, J.M.C. (eds). (1989). Lipid peroxidation: a radical chain reaction. In: Free Radicals in Biology and Medicine. 2nd edn. Clarendon Press, Oxford, pp. 188–276.

    Google Scholar 

  • Heaton, M.B., Madoesky, I., Paiva, M., and Siler-Marsiglio, K.I. (2004). Vitamin E amelioration of ethanol neurotoxicity involves modulation of apoptosis-related protein levels in neonatal rat cerebellar granule cells. Dev. Brain Res. 150:117–124.

    Article  CAS  Google Scholar 

  • Heaton, M.B., Moore, D.B., Paiva, M., Gibbs, T., and Bernard, O. (1999). Bcl-2 overexpression protects the neonatal cerebellum from ethanol neurotoxicity. Brain Res. 817:13–18.

    Article  CAS  PubMed  Google Scholar 

  • Heaton, M.B., Paiva, M., Madosky, I., Mayer, J., and Moore, D.B. (2003). Effects of ethanol on neurotrophic factors, apoptosis-related proteins, endogenous antioxidants, and reactive oxygen species in neonatal striatum: relationship to periods of vulnerability. Dev. Brain Res. 140:237–252.

    Article  CAS  Google Scholar 

  • Heaton, M.B., Paiva, M., Madosky, I., and Shaw, G. (2003). Ethanol effects on neonatal rat cortex: comparative analysis of neurotrophic factors, apoptosis-related proteins, and oxidative processes during vulnerable and resistant periods. Dev. Brain Res. 145:249–262.

    Article  CAS  Google Scholar 

  • Heaton, M.B., Paiva, M., Mayer, J., and Miller, R. (2002). Ethanol-mediated generation of reactive oxygen species in developing rat cerebellum. Neurosci. Lett. 334:83–86.

    Article  CAS  PubMed  Google Scholar 

  • Henderson, G.I., Chen, J.J., and Schenker, S. (1999). Ethanol, Oxidative stress, reactive aldehydes, and the fetus. Front. Biosci. 4:541–550.

    Article  Google Scholar 

  • Henderson, G.I., Devi, B.G., Perez, A., and Schenker, S. (1995). In utero ethanol exposure elicits oxidative stress in the rat fetus. Alcoholism: Clin. Exp. Res. 19:714–720.

    Article  CAS  Google Scholar 

  • Hirrlinger, J., Schulz, J.B., and Dringen, R. (2002). Glutathione release from cultured brain cells: multidrug resistance protein 1 mediates the release of GSH from rat astroglial cells. J. Neurosci. Res. 69:318–326.

    Article  CAS  PubMed  Google Scholar 

  • Horvitz, H.R., Sternberg, P.W., Greenwald, I.S., Fixsen, W., and Ellis, H.M. (1983). Mutations that affect neural cell lineages and cell fates during the development of the nematode Caenorhabditis elegans. Cold Springs Harbor Symp. Quant. Biol. 48:453–463.

    Article  Google Scholar 

  • Inoue, M., Nakamura, K., Iwahashi, K., Ameno, K., Itoh, M., and Suwaki, H. (2002). Changes of bcl-2 and bax mRNA expressions in the ethanol-treated mouse brain. Nihon Arukoru Yakubutsu Igakkai Zasshi 37:120–129.

    CAS  PubMed  Google Scholar 

  • Jacobs, J.S. and Miller, M.W. (2001). Proliferation and death of cultured fetal neocortical neurons: effects of ethanol on the dynamics of cell growth. J. Neurocytol. 30:391–401.

    Article  CAS  PubMed  Google Scholar 

  • Jones, K.L., Smith, D.L., Ulleland, C.W., and Streissguth, A.P. (1973). Pattern of malformations in offspring of chronic alcoholics. Lancet 2:999–1000.

    Article  Google Scholar 

  • Kerr, J.F., Wyllie, A.H., and Currie, A.R. (1972). Apoptosis: a basic biological phenomenon with —ranging implications in tissue kinetics. Brit. J. Cancer 26:239–257.

    Article  CAS  PubMed  Google Scholar 

  • Kuan, C.Y., Roth, K.A., Flavell, R.A., and Rakic, P. (2000). Mechanisms of programmed cell death in the developing brain. Trends Neurosci. 23:291–297.

    Article  CAS  PubMed  Google Scholar 

  • Kuida, K., Haydar, A., Kuan, C.Y., Gu, Y., Taya, C., Karasuyama, H., Su, M.S., Rakic, P., and Flavell, R.A. (1998). Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94:325–337.

    Article  CAS  PubMed  Google Scholar 

  • Kukielka, E., Dicker, E., and Cederbaum, A. (1994). Increased production of reactive oxygen species by rat liver mitochondria after chronic ethanol treatment. Arch. Biochem. Biophys. 309:377–386.

    Article  CAS  PubMed  Google Scholar 

  • Kumar, S. (2007). Caspases and their many biological functions. Cell Death Diff. 14:66–72

    Article  CAS  Google Scholar 

  • Lamarche, F., Signorini-Allibe, N., Gonthier, B., and Barret, L. (2004). Influence of vitamin E, sodium selenite, and astrocyte-conditioned medium on neuronal survival after chronic exposure to ethanol. Alcohol 33:127–138.

    CAS  PubMed  Google Scholar 

  • Lemoine, P., Harrousseau, H., Borteyro, J.P., and Menuer, J.C. (1968). Les enfants de parents alcoholiques; Anomalies observees a propos de 127 cas. Quest Med. 21:467.

    Google Scholar 

  • Liebler, D.C. and Burr, J.A. (1992). Oxidation of vitamin E during iron-catalyzed lipid peroxidation: Evidence for electron-transfer reactions of the tocoperoxyl radical. Biochemistry 31:8278–8284.

    Article  CAS  PubMed  Google Scholar 

  • Light, K.E., Belcher, S.M., and Pierce, D.R. (2002). Time course and manner of Purkinje neuron death following a single ethanol exposure on postnatal day 4 in the developing rat. Neuroscience 114:327–337.

    Article  CAS  PubMed  Google Scholar 

  • Liu, X., Kim, C.N., Yang, J., Jemmerson, R., and Wang, X. (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:47–157.

    Article  Google Scholar 

  • Lossi, L. and Merighi, A. (2003). In vivo cellular and molecular mechanisms of neuronal apoptosis in the mammalian CNS. Prog. Neurobiol. 69:287–312.

    Article  CAS  PubMed  Google Scholar 

  • Lovell, MA., Markesbery, WR. (2006). Amyloid beta peptide, 4-hydroxynonenal and apoptosis. Current Alzheimer Research. 3(4):359–64.

    Article  CAS  PubMed  Google Scholar 

  • Maisonpierre, P.C., Belluscio, L.F., Alderson, R.F., Wiegand, S.J., Furth, M.E., Landsay, R.M., and Yancopolos, G.D. (1990). NT-3, BDNF and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron 5:501–509.

    Article  CAS  PubMed  Google Scholar 

  • Mariucci, G., Ambrosini, M.V., Colarieti, L., and Bruschelli, G. (1990). Differential changes in Cu, Zn and Mn superoxide dismutase activity in developing rat brain and liver. Experientia 46:753–755.

    Article  CAS  PubMed  Google Scholar 

  • Martin, L.J. (2001). Neuronal cell death in nervous system development, disease, and injury. Intl. J. Mol. Med. 7:455–478.

    CAS  Google Scholar 

  • Meister, A. and Anderson, M.E. (1983). Glutathione. Ann. Rev. Biochem. 52:711–760.

    Article  CAS  PubMed  Google Scholar 

  • Miller MW (1992) Effects of prenatal exposure to ethanol on cell proliferation and neuronal migration. In: Miller MW (ed) Development of the Central Nervous System: Effects of Alcohol and Opiates, Wiley-Liss, New York. pp 47–69.

    Google Scholar 

  • Miller, MW. (1995a). Effect of pre- or postnatal exposure to ethanol on the total number of neurons in the principal sensory nucleus of the trigeminal nerve: cell proliferation versus neuronal death. Alcohol Clin Exp Res 19:1359–1364.

    Article  CAS  Google Scholar 

  • Miller, M.W. (1995b). Relationship of time of origin and death of neurons in rat somatosensory cortex: barrel versus septal cortex and projection versus local circuit neurons. J. Comp. Neurol. 355:6–14.

    Article  CAS  Google Scholar 

  • Mitchell, E.S. and Snyder-Keller, A. (2003). c-fos and cleaved caspase-3 expression after perinatal exposure to ethanol, cocaine, or the combination of both drugs. Dev. Brain Res. 147:107–117.

    Article  CAS  Google Scholar 

  • Mitchell, J.J., Paiva, M., and Heaton, M.B. (1999). The antioxidants vitamin E and β-carotene protect against ethanol-induced neurotoxicity in embryonic rat hippocampal cultures. Alcohol 17:163–168.

    Article  CAS  PubMed  Google Scholar 

  • Montoliu, C., Sancho-Tello, M., Azorin, I., Burgal, M., Valles, S., Renau-Piqueras, J., Guerri, C. (1995). Ethanol increases cytochrome P4502E1 and induces oxidative stress in astrocytes. J Neurochem 65:2561–2570.

    Article  CAS  PubMed  Google Scholar 

  • Mooney, S.M. and Miller, M.W. (2001). Effects of prenatal exposure to ethanol on the expression of bcl-2, bax and caspase 3 in the developing rat cerebral cortex and thalamus. Brain Res. 911:71–81.

    Article  CAS  PubMed  Google Scholar 

  • Moore, D.B., Walker, D.W., and Heaton, M.B. (1999). Neonatal ethanol exposure alters bcl-2 family mRNA levels in the rat cerebellar vermis. Alcoholism: Clin. Exp. Res. 23:1251–1261.

    Article  CAS  Google Scholar 

  • Munim, A., Asayama, K., Dobashi, K., Suzuki, K., Kawaoi, A., and Kato, K. (1992). Immunohistochemical localization of superoxide dismutases in fetal and neonatal rat tissues. J. Histochem. Cytochem. 40:1705–1713.

    Article  CAS  PubMed  Google Scholar 

  • Nordmann, R., Riviere, C., and Rouach, H. (1990). Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues. Alcohol Alcohol. 25:231–237.

    CAS  PubMed  Google Scholar 

  • Obernier, J.A., Bouldin, T.W., and Crews, F.T. (2002). Binge ethanol exposure in adult rats causes necrotic cell death. Alcoholism: Clin. Exp. Res. 26:547–557.

    Article  CAS  Google Scholar 

  • Olney, J.W., Tenkova, T., Dikranian, K., Muglia, L.J., Jermakowicz, W.J., D’Sa, C., and Roth, K.A. (2002). Ethanol-induced caspase-3 activation in the in vivo developing mouse brain. Neurobiol. Dis. 9:205–219.

    Article  CAS  PubMed  Google Scholar 

  • Polster, B.M., and Fiskum, G. (2004). Mitochondrial mechanisms of neural cell apoptosis. J. Neurochem. 90:1281–1289.

    Article  CAS  PubMed  Google Scholar 

  • Rajgopal, Y., Chetty, C.S., and Vemuri, M.C. (2003). Differential modulation of apoptosis-associated proteins by ethanol in rat cerebral cortex and cerebellum. Eur. J. Pharmacol. 470:117–124.

    Article  CAS  PubMed  Google Scholar 

  • Ramachandran, V., Perez, A., Chen, J., Senthil, D., Schenker, S., and Henderson, G.I. (2001). In utero ethanol exposure causes mitochondrial dysfunction which can result in apoptotic cell death in fetal brain: A potential role for 4-hydroxynonenal. Alcoholism: Clin. Exp. Res. 25:862–871.

    Article  CAS  Google Scholar 

  • Ramachandran, V., Watts, L.T., Maffi, S.K., Chen, J., Schenker, S., and Henderson, G. (2003). Ethanol-induced oxidative stress precedes mitochondrially mediated apoptotic death of cultured fetal cortical neurons. J. Neurosci. Res. 74:577–588.

    Article  CAS  PubMed  Google Scholar 

  • Rathinam, M.L., Watts, L.T., Stark, A.A., Mahimaimathan, L., Stewart, J., Schenker, S., and Henderson, G.I. (2006). Astrocyte control of fetal cortical neuron glutathione homeostasis: Up-regulation by ethanol. J. Neurochem. 96:1289–1300.

    Article  CAS  PubMed  Google Scholar 

  • Renis, M., Calabrese, V., Russo, A., Calderone, A., Barcellona, M.L., and Rizza, V. (1996). Nuclear DNA strand breaks during ethanol-induced oxidative stress in rat brain. F.E.B.S. Lett. 390:153–156.

    Article  CAS  Google Scholar 

  • Reyes, E., Ott, S., Robinson, B. (1993). Effects of in utero administration of alcohol on glutathione levels in brain and liver. Alcohol Clin Exp Res 17:877–881.

    Article  CAS  PubMed  Google Scholar 

  • Ribiere, C., Hininger, I., Saffar-Boccara, C., Sabourault, D., and Nordmann, R. (1994). Mitochondrial respiratory activity and superoxide radical generation in the liver, brain, and heart after chronic ethanol intake. Biochem. Pharmacol. 47:1827–1833.

    Article  CAS  PubMed  Google Scholar 

  • Rohlmann, A. and Wolff, J.R. (1996). Subcellular topography and plasticity of gap junction distribution on astrocytes. In: Spray, D.C., Dermietzel, R. (eds.), Gap Junctions in the Nervous System, Landes, Austin, TX, pp.175–192.

    Google Scholar 

  • Rouach, H., Park, M.K., Orfanelli, M.T., Janvier, B., and Nordmann, R. (1987). Ethanol-induced oxidative stress in the rat cerebellum. Alcohol Alcohol. 1:207–211.

    CAS  Google Scholar 

  • Rushmore, T.H., Morton, M.R., and Pickett, C.P. (1991). The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J. Biol. Chem. 266:11632–11639.

    CAS  PubMed  Google Scholar 

  • Ryter, S.W., Kim, H.P., Hoetzel, A., Park, J.W., Nakahira, K., Wang, X., and Choi, A.M.K. (2007). Mechanisms of cell death in oxidative stress. Antioxid. Redox Signal. 9:49–89.

    Article  CAS  PubMed  Google Scholar 

  • Sagara, J., Miura, K., Bannai, S. Maintenance of neuronal glutathione by glial cells. (1993) J Neurochem 61:1672–1676.

    Article  CAS  PubMed  Google Scholar 

  • Saito, M., Saito, M., Berg, M.J., Guidotti, A., and Marks, N. (1999). Gangliosides attenuate ethanol-induced apoptosis in rat cerebellar granule neurons. Neurochem. Res. 24:1107–1115.

    Article  CAS  PubMed  Google Scholar 

  • Sastry, P.S. and Rao, K.S. (2000). Apoptosis and the nervous system. J. Neurochem. 74:1–20.

    Article  CAS  PubMed  Google Scholar 

  • Schenker, S., Becker, H.C., Randall, C., Phillips, D.K., Baskin, G.S., and Henderson, G.H. (1990). Fetal Alcohol Syndrome: Current status of pathogenesis. Alcoholism: Clin. Exp. Res. 14:635–647.

    Article  CAS  Google Scholar 

  • Schulz, J.B., Lindenau, J., Seyfried, J. and Dichgans, J. (2000). Glutathione, oxidative stress, and neurodegeneration. Eur. J. Biochem. 267:4904–4911.

    Article  CAS  PubMed  Google Scholar 

  • Shaw, S., Rubin, K.P., and Lieber, C.S. (1983). Depressed hepatic glutathione and increased diene conjugates in alcoholic liver disease. Evidence of lipid peroxidation. Digest. Dis. Sci. 28:585–589.

    Article  CAS  Google Scholar 

  • Siler-Marsiglio, K.I., Shaw, G., and Heaton, M.B. (2004). Pycnogenol and vitamin E inhibit ethanol-induced apoptosis in rat cerebellar granule cells. J. Neurobiol. 59:261–271.

    Article  CAS  PubMed  Google Scholar 

  • Spierlings, D., McStay, G., Saleh, M., Bender, C., Chipuk, J., Maurer, U., and Green, D.R. (2005). Connected to death: The (unexpurgated) mitochondrial pathway of apoptosis. Science 310:66–67.

    Article  CAS  Google Scholar 

  • Streissguth, A.P., Barr, H.M., and Sampson, P.D. (1990). Moderate prenatal alcohol exposure: effects on child IQ and learning problems at age 72 years. Alcoholism: Clin. Exp. Res. 14:662–669.

    Article  CAS  Google Scholar 

  • Suthanthiran, M., Anderson, M.E., Sharma, V.K., and Meister, A. (1990). Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc. Natl. Acad. Sci. USA. 87:3343–3347.

    Article  CAS  PubMed  Google Scholar 

  • Tanaka, J., Toku, K., Zhang, B., Isihara, K., Sakanaka, M., and Maeda, N. (1999). Astrocytes prevent neuronal death induced by reactive oxygen and nitrogen species. Glia 28:85–96.

    Article  CAS  PubMed  Google Scholar 

  • Timmer, J.C. and Salvesen, G.S. (2007). Caspase substrates. Cell Death Diff. 14:66–72.

    Article  CAS  Google Scholar 

  • Tsukamoto, H. (1993). Oxidative stress, antioxidants, and alcoholic liver fibrogenesis. Alcohol 10:465–467.

    Article  CAS  PubMed  Google Scholar 

  • Uchida, K., Szweda, L.I., Chae, H.-Z., and Stadtman, E.R. (1993). Immunochemical detection of 4-hydroxynonenal protein adducts in oxidized hepatocytes. Proc. Natl. Acad. Sci. USA 90:8742–8746.

    Article  CAS  PubMed  Google Scholar 

  • Vaudry, D., Rousselle, C., Basille, M., Falluel-Morel, A., Pamantung, T.F., Fontaine, M., Fournier, A., Vaudry, H., and Gonzalez, B.J. (2002). Pituitary adenylate cyclase-activating polypeptide protects rat cerebellar granule neurons against ethanol-induced apoptotic cell death. Proc. Natl. Acad. Sci. USA 99:6398–6403.

    Article  CAS  PubMed  Google Scholar 

  • Wang, X.F. and Cynader, M.S. (2000). Astrocytes provide cysteine to neurons by releasing glutathione. J. Neurochem. 74:1434–1442.

    Article  CAS  PubMed  Google Scholar 

  • Wass, T.S., Simmons, R.W., Thomas, J.D., and Riley, E.P. (2002). Timing accuracy and variability in children with prenatal exposure to alcohol. Alcoholism: Clin. Exp. Res. 26:1887–1896.

    Article  CAS  Google Scholar 

  • Watts, L.T., Rathinam, M.L., Schenker, S., and Henderson, G.I. (2005). Astrocytes protect neurons from ethanol-induced oxidative stress and apoptotic death. J. Neurosci. Res. 80:655–666.

    Article  CAS  PubMed  Google Scholar 

  • Wozniak, D.F., Hartman, R.E., Boyle, M.P., Vogt, S.K., Brooks, A.R., Tenkova, T., Young, C., Olney, J.W., and Muglia, L.J. (2004). Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning/memory deficits in juveniles followed by progressive functional recovery in adults. Neurobiol. Dis. 17:403–414.

    Article  CAS  PubMed  Google Scholar 

  • Young, C., Klocke, B.J., Tenkova, T., Choi, J., Labruyere, J., Qin, Y.Q., Holtzman, D.M., Roth, K.A., and Olney, J.W. (2003). Ethanol-induced neuronal apoptosis in vivo requires BAX in the developing mouse brain. Cell Death Differ. 10:1148–1155.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology and Nutrition, University of Texas Health Science Center, San Antonio, Texas, USA

    George I. Henderson, Jennifer Stewart & Steven Schenker

Authors
  1. George I. Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Steven Schenker
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medicine & Science, Chicago Medical School, Rosalind Franklin University of, Green Bay Rd. 3333, North Chicago, 60064, Illinois, USA

    David W. McCandless

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Henderson, G.I., Stewart, J., Schenker, S. (2009). Alcohol, Neuron Apoptosis, and Oxidative Stress. In: McCandless, D. (eds) Metabolic Encephalopathy. Springer, New York, NY. https://doi.org/10.1007/978-0-387-79112-8_13

Download citation

Publish with us

Policies and ethics

Search

Navigation