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Microarray Analysis of Gene Expression in Rat Hippocampus After Chronic Ethanol Treatment

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Abstract

It is thought that changes in gene expression in the brain mediate chronic ethanol-induced complex behaviors such as tolerance, dependence, and sensitization, and also relate to ethanol-induced brain toxicity. Using high-density filter-based cDNA microarrays (GeneFilters), we analyzed the expression of over 5000 genes in the dorsal hippocampus of rats treated with 12% ethanol or tap water for 15 months. Ethanol-induced changes in gene expression were particularly prominent in two groups of genes. One group consisted of oxidoreductases, including ceruloplasmin, uricase, branched-chain alpha-keto acid dehydrogenase, NADH ubiquinone oxidoreductase, P450, NAD+-isocitrate dehydrogenase, and cytochrome c oxidase, which may be related to ethanol-induced oxidative stress. The other group of genes included ADP-ribosylation factor, RAS related protein rab10, phosphatidylinositol 4-kinase, dynein-associated polypeptides, and dynamin-1, which seem to be involved in membrane trafficking. The results may reveal some of the pathways involved in ethanol-induced pathophysiological changes.

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REFERENCES

  1. Berman, R. F. and Hannigan, J. H. 2000. Effects of prenatal alcohol exposure on the hippocampus: Spatial behavior, electrophysiology, and neuroanatomy. Hippocampus 10:94-110.

    Google Scholar 

  2. Korbo, L. 1999. Glial cell loss in the hippocampus of alcoholics. Alcohol Clin. Exp. Res. 23:164-168.

    Google Scholar 

  3. Lukoyanov, N. V., Madeira, M. D., and Paula-Barbosa, M. M. 1999. Behavioral and neuroanatomical consequences of chronic ethanol intake and withdrawal. Physiol. Behav. 66:337-346.

    Google Scholar 

  4. 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. FEBS Lett. 390:153-151.

    Google Scholar 

  5. Matthews, D. B., Devaud, L. L., Fritschy, J. M., Sieghart, W., and Morrow, A. L. 1998. Differential regulation of GABA(A) receptor gene expression by ethanol in the rat hippocampus versus cerebral cortex. J. Neurochem. 70:1160-1166.

    Google Scholar 

  6. Naassila, M. and Daoust, M. 2002. Effect of prenatal and postnatal ethanol exposure on the developmental profile of mRNAs encoding NMDA receptor subunits in rat hippocampus. J. Neurochem. 80:850-860.

    Google Scholar 

  7. Bruckner, M. K., Rossner, S., and Arendt, T. 1997. Differential changes in the expression of AMPA receptors genes in rat brain after chronic exposure to ethanol: An in situ hybridization study. J. Hirnforsch. 38:369-376.

    Google Scholar 

  8. Nevo, I., Langlois, X., Laporte, A. M., Kleven, M., Koek, W., Lima, L., Maudhuit, C., Martres, M. P., and Hamon, M. 1995. Chronic alcoholization alters the expression of 5-HT1A and 5-HT1B receptor subtypes in rat brain. Eur. J. Pharmacol. 281:229-223.

    Google Scholar 

  9. Upadhya, S. C., Tirumalai, P. S., Boyd, M. R., Mori, T., and Ravindranath, V. 2000. Cytochrome P450 2E (CYP2E) in brain: Constitutive expression, induction by ethanol and localization by fluorescence in situ hybridization. Arch. Biochem. Biophys. 373:23-34.

    Google Scholar 

  10. Calabrese, V., Renis, M., Calderone, A., Russo, A., Reale, S., Barcellona, M. L., and Rizza, V. 1998. Stress proteins and SH-groups in oxidant-induced cellular injury after chronic ethanol administration in rat. Free Radic. Biol. Med. 24:1159-1167.

    Google Scholar 

  11. Chen, W., Hardy, P., and Wilce, P. A. 1997. Differential expression of mitochondrial NADH dehydrogenase in ethanol-treated rat brain: revealed by differential display. Alcohol Clin. Exp. Res. 21:1053-1056.

    Google Scholar 

  12. Kim, J. H., Kim, J. E., Kim, H. J., Roh, G. S., Yoo, J. M., Kang, S. S., Cho, Y. Y., Cho, G. J., and Choi, W. S. 2001. Ethanol decreases the expression of mitochondrial cytochrome c oxidase mRNA in the rat. Neurosci. Lett. 305:107-110.

    Google Scholar 

  13. Tapia-Arancibia, L., Rage, F., Givalois, L., Dingeon, P., Arancibia, S., and Beauge, F. 2001. Effects of alcohol on brain-derived neurotrophic factor mRNA expression in discrete regions of the rat hippocampus and hypothalamus. J. Neurosci. Res. 63:200-208.

    Google Scholar 

  14. Putzke, J., De Beun, R., Schreiber, R., De Vry, J., Tolle, T. R., Zieglgansberger, W., and Spanagel, R. 1998. Long-term alcohol self-administration and alcohol withdrawal differentially modulate microtuble-associated protein 2 (MAP2) gene expression in the rat brain. Brain Res. Mol. Brain Res. 62:196-205.

    Google Scholar 

  15. Schafer, G. L., Crabbe, J. C., and Wiren, K. M. 2001. Ethanol-regulated gene expression of neuroendocrine specific protein in mice: Brain region and genotype specificity. Brain Res. 897:139-149.

    Google Scholar 

  16. Thibault, C., Lai, C., Wilke, N., Duong, B., Olive, M. F., Rahman, S., Dong, H., Hodge, C. W., Lockhart, D. J., and Miles, M. F. 2000. Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression. Mol. Pharmacol. 52:1593-1600.

    Google Scholar 

  17. Lewohl, J. M., Wang, L., Miles, M. F., Zhang, L., Dodd, P. R., and Harris, R. A. 2000. Gene expression in human alcoholism: microarray analysis of frontal cortex. Alcohol Clin. Exp. Res. 24:1873-1882.

    Google Scholar 

  18. Lewohl, J. M., Dodd, P. R., Mayfield, R. D., and Harris, R. A. 2001. Application for DNA microarrays to study human alcoholism. J. Biomed. Sci. 8:28-36.

    Google Scholar 

  19. Leonard, B. E. 1986. Is ethanol a neurotoxin?: the effects of ethanol on neuronal structure and function. Alcohol Alcohol 21:325-338.

    Google Scholar 

  20. Neiman, J. 2000. Neurological complications of drug abuse: pathophysiological mechanisms. Eur. J. Neurol. 7:595-606.

    Google Scholar 

  21. Lang, D., Beno, M., Fifkova, E., and Eason, H. 1997. Fine structure of hippocampal dendrites in the dentate fascia of LS/ SS-mice after chronic ethanol treatment. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 21:1031-1042.

    Google Scholar 

  22. Lukoyanov, N. V., Brandao, F., Cadete-Leite, A., Madeira, M. D., and Paula-Barbosa, M. M. 2000. Synaptic reorganization in the hippocampal formation of alcohol-fed rats may compensate for functional deficits related to neuronal loss. Alcohol 20:139-148.

    Google Scholar 

  23. Richard, D., Clavel, S., Huang, Q., Sanchis, D., and Ricquier, D. 2001. Uncoupling protein 2 in the brain: Distribution and function. Biochem. Soc. Trans. 29:812-817.

    Google Scholar 

  24. Ray, S. K., Fidan, M., Nowak, M. W., Wilford, G. G., Hogan, E. L., and Banic, N. L. 2000. Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC12 cells. Brain Res. 852:326-334.

    Google Scholar 

  25. Bondy, S. C. and Pearson, K. R. 1993. Ethanol-induced oxidative stress and nutritional status. Alcohol Clin. Exp. Res. 17:651-654.

    Google Scholar 

  26. Wenisch, S., Steinmetz, T., Fortmann, B., Leiser, R., and Bitsch, I. 1996. Can megadoses of thiamine prevent ethanol-induced damages of rat hippocampal CA1 pyramidal neurones? Z. Ernahrungswiss 35:266-272.

    Google Scholar 

  27. Koch, O., Farre, S., De Leo, M. E., Palozza, P., Palazzotti, B., Borrelo, S., Palombini, G., Cravero, A., and Galeotti, T. 2000. Regulation of manganese superoxide dismutase (MnSOD) in chronic experimental alcoholism: effects of vitamin E-supplemented and-deficient diets. Alcohol 35:159-163.

    Google Scholar 

  28. Torok, N., Marks, D., Hsiao, K., Oswald, B. J., and McNiven, M. A. 1997. Vesicle movement in rat hepatocytes is reduced by ethanol exposure: alterations in microtubule-based motor enzymes. Gastroenterology 113:1938-1948.

    Google Scholar 

  29. McVicker, B. L. and Casey, C. A. 1999. Ethanol-impaired hepatic protein trafficking: Concepts from the asialoglycoprotein receptor system. Clin. Biochem. 32:557-561.

    Google Scholar 

  30. Gulya, K., Orpana, A. K., Sikela, J. M., and Hoffman, P. L. 1993. Prodynorphin and vasopressin mRNA levels are differentially affected by chronic ethanol ingestion in the mouse. Brain Res. Mol. Brain Res. 20:1-8.

    Google Scholar 

  31. Xu, Y., Ehringer, M., Yang, F., and Sikela, J. M. 2001. Comparison of global brain gene expression profiles between inbred long-sleep and inbred short-sleep mice by high-density gene array hybridization. Alcohol Clin. Exp. Res. 25:810-818.

    Google Scholar 

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Saito, M., Smiley, J., Toth, R. et al. Microarray Analysis of Gene Expression in Rat Hippocampus After Chronic Ethanol Treatment. Neurochem Res 27, 1221–1229 (2002). https://doi.org/10.1023/A:1020937728506

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  • DOI: https://doi.org/10.1023/A:1020937728506

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