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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Effects of chronic alcohol consumption on expression levels of APP and Aβ-producing enzymes

  • Kim, Sae-Rom (School of Pharmacy, Sungkyunkwan University) ;
  • Jeong, Hye-Young (School of Pharmacy, Sungkyunkwan University) ;
  • Yang, Sung-Hee (School of Pharmacy, Sungkyunkwan University) ;
  • Choi, Sung-Pil (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Seo, Min-Young (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Yun, Young-Kwang (School of Pharmacy, Sungkyunkwan University) ;
  • Choi, Yu-Ri (School of Pharmacy, Sungkyunkwan University) ;
  • Baik, Sang-Ha (School of Pharmacy, Sungkyunkwan University) ;
  • Park, Jong-Sung (School of Pharmacy, Sungkyunkwan University) ;
  • Gwon, A-Ryeong (School of Pharmacy, Sungkyunkwan University) ;
  • Yang, Dong-Kwon (Department of Life Science, Gwangju Institute of Science and Technology) ;
  • Lee, Chan-Ho (School of Pharmacy, Sungkyunkwan University) ;
  • Lee, Sun-Mee (School of Pharmacy, Sungkyunkwan University) ;
  • Park, Kye-Won (Department of Food Science and Biotechnology, Sungkyunkwan University) ;
  • Jo, Dong-Gyu (School of Pharmacy, Sungkyunkwan University)
  • Received : 2010.12.30
  • Accepted : 2010.12.31
  • Published : 2011.02.28
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Abstract

Chronic alcohol consumption contributes to numerous diseases, including cancers, cardiovascular diseases, and liver cirrhosis. Epidemiological studies have shown that excessive alcohol consumption is a risk factor for dementia. Along this line, Alzheimer's disease (AD) is the most common form of dementia and is caused by the accumulation of amyloid-$\beta$ ($A{\beta}$ plaques in neurons. In this study, we hypothesized that chronic ethanol consumption is associated with pathological processing of APP in AD. To investigate the relationship between chronic alcohol consumption and $A{\beta}$ production, brain samples from rats fed an alcohol liquid diet for 5 weeks were analyzed. We show that the expression levels of APP, BACE1, and immature nicastrin were increased in the cerebellum, hippocampus, and striatum of the alcohol-fed group compared to the control group. Total nicastrin and PS1 levels were induced in the hippocampus of alcohol-fed rats. These data suggest that the altered expression of APP and $A{\beta}$-producing enzymes possibly contributes to the chronic alcohol consumption-mediated pathogenesis of AD.

Keywords

References

  1. Kalaria, R. N., Maestre, G. E., Arizaga, R., Friedland, R. P., Galasko, D., Hall, K., Luchsinger, J. A., Ogunniyi, A., Perry, E. K., Potocnik, F., Prince, M., Stewart, R., Wimo, A., Zhang, Z. X. and Antuono, P. (2008) Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol. 7, 812-826. https://doi.org/10.1016/S1474-4422(08)70169-8
  2. Tanzi, R. E. and Bertram, L. (2005) Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 120, 545-555. https://doi.org/10.1016/j.cell.2005.02.008
  3. Mattson, M. P. (2004) Pathways towards and away from Alzheimer's disease. Nature 430, 631-639. https://doi.org/10.1038/nature02621
  4. Gasior, M., Rogawski, M. A. and Hartman, A. L. (2006) Neuroprotective and disease-modifying effects of the ketogenic diet. Behav. Pharmacol. 17, 431-439. https://doi.org/10.1097/00008877-200609000-00009
  5. Lau, F. C., Shukitt-Hale, B. and Joseph, J. A. (2007) Nutritional intervention in brain aging: reducing the effects of inflammation and oxidative stress. Subcell. Biochem. 42, 299-318. https://doi.org/10.1007/1-4020-5688-5_14
  6. Dosunmu, R., Wu, J., Basha, M. R. and Zawia, N. H. (2007) Environmental and dietary risk factors in Alzheimer's disease. Expert Rev. Neurother. 7, 887-900. https://doi.org/10.1586/14737175.7.7.887
  7. Panza, F., Capurso, C. and Solfrizzi, V. (2008) Alcohol use, thiamine deficiency, and cognitive impairment. JAMA 299, 2853-2854; author reply 2854-2855. https://doi.org/10.1001/jama.299.24.2853
  8. Ramesh, B. N., Rao, T. S., Prakasam, A., Sambamurti, K. and Rao, K. S. Neuronutrition and Alzheimer's disease. J. Alzheimers. Dis. 19, 1123-1139.
  9. Ruitenberg, A., van Swieten, J. C., Witteman, J. C., Mehta, K. M., van Duijn, C. M., Hofman, A. and Breteler, M. M. (2002) Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet 359, 281-286. https://doi.org/10.1016/S0140-6736(02)07493-7
  10. Mukamal, K. J., Kuller, L. H., Fitzpatrick, A. L., Longstreth, W. T., Jr., Mittleman, M. A. and Siscovick, D. S. (2003) Prospective study of alcohol consumption and risk of dementia in older adults. JAMA 289, 1405-1413. https://doi.org/10.1001/jama.289.11.1405
  11. Galanis, D. J., Joseph, C., Masaki, K. H., Petrovitch, H., Ross, G. W. and White, L. (2000) A longitudinal study of drinking and cognitive performance in elderly Japanese American men: the Honolulu-Asia Aging Study. Am. J. Public. Health 90, 1254-1259. https://doi.org/10.2105/AJPH.90.8.1254
  12. Luchsinger, J. A. and Mayeux, R. (2004) Cardiovascular risk factors and Alzheimer's disease. Curr. Atheroscler. Rep. 6, 261-266. https://doi.org/10.1007/s11883-004-0056-z
  13. Truelsen, T., Thudium, D. and Gronbaek, M. (2002) Amount and type of alcohol and risk of dementia: the Copenhagen City Heart Study. Neurology 59, 1313-1319. https://doi.org/10.1212/01.WNL.0000031421.50369.E7
  14. Jaatinen, P., Riikonen, J., Riihioja, P., Kajander, O. and Hervonen, A. (2003) Interaction of aging and intermittent ethanol exposure on brain cytochrome c oxidase activity levels. Alcohol. 29, 91-100. https://doi.org/10.1016/S0741-8329(03)00002-8
  15. de la Monte, S. M., Vonsattel, J. P. and Richardson, E. P., Jr. (1988) Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington's disease. J. Neuropathol. Exp. Neurol. 47, 516-525. https://doi.org/10.1097/00005072-198809000-00003
  16. Mann, K., Agartz, I., Harper, C., Shoaf, S., Rawlings, R. R., Momenan, R., Hommer, D. W., Pfefferbaum, A., Sullivan, E. V., Anton, R. F., Drobes, D. J., George, M. S., Bares, R., Machulla, H. J., Mundle, G., Reimold, M. and Heinz, A. (2001) Neuroimaging in alcoholism: ethanol and brain damage. Alcohol. Clin. Exp. Res. 25, 104S-109S. https://doi.org/10.1111/j.1530-0277.2001.tb02383.x
  17. Ferrer, I., Fabregues, I., Pineda, M., Gracia, I. and Ribalta, T. (1984) A Golgi study of cerebellar atrophy in human chronic alcoholism. Neuropathol. Appl. Neurobiol. 10, 245-253. https://doi.org/10.1111/j.1365-2990.1984.tb00357.x
  18. Fox, J. H., Ramsey, R. G., Huckman, M. S. and Proske, A. E. (1976) Cerebral ventricular enlargement. Chronic alcoholics examined by computerized tomography. JAMA 236, 365-368. https://doi.org/10.1001/jama.236.4.365
  19. Sullivan, E. V., Marsh, L., Mathalon, D. H., Lim, K. O. and Pfefferbaum, A. (1995) Anterior hippocampal volume deficits in nonamnesic, aging chronic alcoholics. Alcohol. Clin. Exp. Res. 19, 110-122. https://doi.org/10.1111/j.1530-0277.1995.tb01478.x
  20. Bleich, S., Sperling, W., Degner, D., Graesel, E., Bleich, K., Wilhelm, J., Havemann-Reinecke, U., Javaheripour, K. and Kornhuber, J. (2003) Lack of association between hippocampal volume reduction and first-onset alcohol withdrawal seizure. A volumetric MRI study. Alcohol Alcohol. 38, 40-44. https://doi.org/10.1093/alcalc/agg017
  21. Kurth, C., Wegerer, V., Reulbach, U., Lewczuk, P., Kornhuber, J., Steinhoff, B. J. and Bleich, S. (2004) Analysis of hippocampal atrophy in alcoholic patients by a Kohonen feature map. Neuroreport 15, 367-371. https://doi.org/10.1097/00001756-200402090-00031
  22. Bleich, S., Wilhelm, J., Graesel, E., Degner, D., Sperling, W., Rossner, V., Javaheripour, K. and Kornhuber, J. (2003) Apolipoprotein E epsilon 4 is associated with hippocampal volume reduction in females with alcoholism. J. Neural. Transm. 110, 401-411. https://doi.org/10.1007/s00702-002-0789-1
  23. Hommer, D., Momenan, R., Kaiser, E. and Rawlings, R. (2001) Evidence for a gender-related effect of alcoholism on brain volumes. Am. J. Psychiatry. 158, 198-204. https://doi.org/10.1176/appi.ajp.158.2.198
  24. Pfefferbaum, A., Lim, K. O., Zipursky, R. B., Mathalon, D. H., Rosenbloom, M. J., Lane, B., Ha, C. N. and Sullivan, E. V. (1992) Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. Alcohol. Clin. Exp. Res. 16, 1078-1089. https://doi.org/10.1111/j.1530-0277.1992.tb00702.x
  25. Teichman, M., Richman, S. and Fine, E. W. (1987) "Dose/duration effect" relationship between alcohol consumption and cerebral atrophy: a psychological and neuroradiological evaluation. Am. J. Drug. Alcohol. Abuse. 13, 357-363. https://doi.org/10.3109/00952998709001519
  26. Kril, J. J. and Homewood, J. (1993) Neuronal changes in the cerebral cortex of the rat following alcohol treatment and thiamin deficiency. J. Neuropathol. Exp. Neurol. 52, 586-593. https://doi.org/10.1097/00005072-199311000-00005
  27. Woo, H. N., Park, J. S., Gwon, A. R., Arumugam, T. V. and Jo, D. G. (2009) Alzheimer's disease and Notch signaling. Biochem. Biophys. Res. Commun. 390, 1093-1097. https://doi.org/10.1016/j.bbrc.2009.10.093
  28. Woo, H. N., Baik, S. H., Park, J. S., Gwon, A. R., Yang, S., Yun, Y. K. and Jo, D. G. (2011) Secretases as therapeutic targets for Alzheimer's disease. Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2010.11.132
  29. Jo, D. G., Arumugam, T. V., Woo, H. N., Park, J. S., Tang, S. C., Mughal, M., Hyun, D. H., Park, J. H., Choi, Y. H., Gwon, A. R., Camandola, S., Cheng, A., Cai, H., Song, W., Markesbery, W. R. and Mattson, M. P. (2010) Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer's disease. Neurobiol. Aging. 31, 917-925. https://doi.org/10.1016/j.neurobiolaging.2008.07.003
  30. Shah, S., Lee, S. F., Tabuchi, K., Hao, Y. H., Yu, C., LaPlant, Q., Ball, H., Dann, C. E., 3rd, Sudhof, T. and Yu, G. (2005) Nicastrin functions as a gamma-secretase-substrate receptor. Cell 122, 435-447. https://doi.org/10.1016/j.cell.2005.05.022
  31. Anttila, T., Helkala, E. L., Viitanen, M., Kareholt, I., Fratiglioni, L., Winblad, B., Soininen, H., Tuomilehto, J., Nissinen, A. and Kivipelto, M. (2004) Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based study. BMJ 329, 539. https://doi.org/10.1136/bmj.38181.418958.BE
  32. Rothman, S. M. and Mattson, M. P. (2010) Adverse stress, hippocampal networks, and Alzheimer's disease. Neuromolecular Med. 12, 56-70. https://doi.org/10.1007/s12017-009-8107-9
  33. Lieber, C. S. and DeCarli, L. M. (1989) Liquid diet technique of ethanol administration: 1989 update. Alcohol Alcohol. 24, 197-211.
  34. Kerai, M. D., Waterfield, C. J., Kenyon, S. H., Asker, D. S. and Timbrell, J. A. (1999) Reversal of ethanol-induced hepatic steatosis and lipid peroxidation by taurine: a study in rats. Alcohol Alcohol. 34, 529-541. https://doi.org/10.1093/alcalc/34.4.529

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