Browse > Article

Ethanol Induces Cell Death by Activating Caspase-3 in the Rat Cerebral Cortex  

Han, Jae Yoon (Department of Anatomy and Neurobiology, College of Medicine, Health Science Institute, Gyeongsang National University)
Joo, Yeon (Department of Anatomy and Neurobiology, College of Medicine, Health Science Institute, Gyeongsang National University)
Kim, Yoon Sook (Department of Anatomy and Neurobiology, College of Medicine, Health Science Institute, Gyeongsang National University)
Lee, Young Ki (Department of Histology, College of Medicine, Jeju National University)
Kim, Hyun Joon (Department of Anatomy and Neurobiology, College of Medicine, Health Science Institute, Gyeongsang National University)
Cho, Gyeong Jae (Department of Anatomy and Neurobiology, College of Medicine, Health Science Institute, Gyeongsang National University)
Choi, Wan Sung (Department of Anatomy and Neurobiology, College of Medicine, Health Science Institute, Gyeongsang National University)
Kang, Sang Soo (Department of Anatomy and Neurobiology, College of Medicine, Health Science Institute, Gyeongsang National University)
Publication Information
Molecules and Cells / v.20, no.2, 2005 , pp. 189-195 More about this Journal
Abstract
Ethanol has long been implicated in triggering apoptotic neurodegeneration. We examined the effects of ethanol on the rat brain during synaptogenesis when a spurt in brain growth occurs. This period corresponds to the first 2 postnatal weeks in rats and is very sensitive to ethanol exposure. Ethanol was administered subcutaneously to 7-day- postnatal rat pups by a dosing regimen of 3 g/kg at 0 h and again at 2 h. Blood ethanol levels peaked ($677{\pm}16.4mg/dl$) at 4 h after the first ethanol administration. The cerebral cortexes of the ethanol-treated group showed several typical symptoms of apoptosis such as chromosome condensation and disintegration of cell bodies. Activated caspase-3 positive cells were found in the cortex within 2 h of the first injection, and reached a peak at 12 h. In addition, TUNEL staining revealed DNA fragmentation in the same regions. These results demonstrate that acute ethanol administration causes neuronal cell death via a caspase-3-dependent pathway within 24 h, suggesting that activation of caspase-3 is a marker of the developmental neurotoxicity of ethanol.
Keywords
Caspase-3; Cell Death; Ethanol; Rat; Synaptogenesis; TUNEL;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 18  (Related Records In Web of Science)
연도 인용수 순위
1 Allan, A. M. and Harris, R. A. (1987) Acute and chronic ethanol treatments alter GABA receptor-operated chloride channels. Pharmacol. Biochem. Behav. 27, 665-670   DOI   ScienceOn
2 Dikranian, K., Ishimaru, M. J., Tenkova, T., Labruyere, J., Qin, Y. Q., et al. (2001) Apoptosis in the in vivo mammalian forebrain. Neurobiol. Dis. 8, 359-379   DOI   ScienceOn
3 Dobbing, J. and Sands, J. (1979) Comparative aspects of the brain growth spurt. Early Hum. Dev. 3, 79-83   DOI   ScienceOn
4 Harris, R. A., Proctor, W. R., McQuilkin, S. J., Klein, R. L., Mascia, M. P., et al. (1995) Ethanol increases GABAA responses in cells stably transfected with receptor subunits. Alcohol Clin. Exp. Res. 19, 226-232   DOI   ScienceOn
5 Hoffman, P. L., Rabe, C. S., Moses, F., and Tabakoff, B. (1989) N-methyl-D-aspartate receptors and ethanol: inhibition of calcium flux and cyclic GMP production. J. Neurochem. 52, 1937-1940   DOI
6 Jakab, M., Weiger, T. M., and Hermann, A. (1997) Ethanol activates maxi $Ca^{2+}$ -activated $K^+$ channels of clonal pituitary (GH3) cells. J. Membr. Biol. 157, 237-245   DOI
7 Janicke, R. U., Ng, P., Sprengart, M. L., and Porter, A. G. (1998) Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis. J. Biol. Chem. 273, 15540-15545   DOI   ScienceOn
8 Olney, J. W., Tenkova, T., Dikranian, K., Muglia, L. J., Jermakowicz, W. J., et al. (2002) Ethanol-induced caspase-3 activation in the in vivo developing mouse brain. Neurobiol. Dis. 9, 205-219   DOI   ScienceOn
9 Sohn, I. P., Ahn, H. J., Park, D. W., Gye, M. C., Jo, D. H., et al. (2002) Amelioration of mitochondrial dysfunction and apoptosis of two-cell mouse embryos after freezing and thawing by the high frequency liquid nitrogen infusion. Mol. Cells 13, 272-280
10 Witt, M. R., Dekermendjian, K., Frandsen, A., Schousboe, A., and Nielsen, M. (1994) Complex correlation between excitatory amino acid-induced increase in the intracellular $Ca^{2+}$ concentration and subsequent loss of neuronal function in individual neocortical neurons in culture. Proc. Natl. Acad. Sci. USA 91, 12303-12307
11 Woodward, J. J. (2000) Ethanol and NMDA receptor signaling. Crit. Rev. Neurobiol. 14, 69-89
12 Famy, C., Streissguth, A. P., and Unis, A. S. (1998) Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects. Am. J. Psychiatry 155, 552-554
13 Yano, S., Tokumitsu, H., and Soderling, T. R. (1998) Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway. Nature 396, 584-587   DOI   ScienceOn
14 Hoffman, P. L. (1995) Glutamate receptors in alcohol withdrawal- induced neurotoxicity. Metab. Brain Dis. 10, 73-79   DOI
15 Lovinger, D. M., White, G., and Weight, F. F. (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243, 1721-1724   DOI
16 Mahalik, T. J. and Owens, G. P. (1997) Cell death in the nervous system. J. Invest. Dermatol. Symp. Proc. 2, 14-18
17 Mehta, A. K. and Ticku, M. K. (1988) Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acidA-gated chloride channels. J. Pharmacol. Exp. Ther. 246, 558-564
18 Alling, C. (1999) The biological mechanisms underlying alcohol dependence. Lakartidningen 96, 3248-3252
19 Mattson, S. N., Jernigan, T. L., and Riley, E. P. (1994) MRI and prenatal alcohol exposure. Alcohol Health Res. World 18, 49-52
20 D'Mello, S. R., Kuan, C. Y., Flavell, R. A., and Rakic, P. (2000) Caspase-3 is required for apoptosis-associated DNA fragmentation but not for cell death in neurons deprived of potassium. J. Neurosci. Res. 59, 24-31   DOI   ScienceOn
21 Dahchour, A., Hoffmanm, A., Deitrich, R., and de Witte, P. (2000) Effects of ethanol on extracellular amino acid levels in high-and low-alcohol sensitive rats: a microdialysis study. Alcohol Alcohol. 35, 548-553   DOI   ScienceOn
22 Schummers, J., Bentz, S., and Browning, M. D. (1997) Ethanol's inhibition of LTP may not be mediated solely via direct effects on the NMDA receptor. Alcohol Clin. Exp. Res. 21, 404-408
23 Solem, M., McMahon, T., and Messing, R. O. (1997) Protein kinase A regulates regulates inhibition of N- and P/Q-type calcium channels by ethanol in PC12 cells. J. Pharmacol. Exp. Ther. 282, 1487-1495
24 Kobayashi, T., Ikeda, K., Kojima, H., Niki, H., Yano, R., et al. (1999) Ethanol opens G-protein-activated inwardly rectifying $K^+$ channels. Nat. Neurosci. 2, 1091-1097   DOI   ScienceOn
25 Streissguth, A. P. and O'Malley, K. (2000) Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders. Semin. Clin. Neuropsychiatry 5, 177-190   DOI
26 Lee, K. H., Kim, K. C., Jung, Y. J., Ham, Y. H., Jang, J. J., et al. (2001) Induction of apoptosis in p53-deficient human hepatoma cell line by wild-type p53 gene transduction: inhibition by antioxidant. Mol. Cells 12, 17-24
27 Lovinger, D. M. and White, G. (1991) Ethanol potentiation of 5- hydroxytryptamine3 receptor-mediated ion current in neuroblastoma cells and isolated adult mammalian neurons. Mol. Pharmacol. 40, 263-270
28 Carta, M., Ariwodola, O. J., Weiner, J. L., and Valenzuela, C. F. (2003) Alcohol potently inhibits the kainate receptordependent excitatory drive of hippocampal interneurons. Proc. Natl. Acad. Sci. USA 100, 6813-6818
29 Fujikawa, D. G., Shinmei, S. S., and Cai, B. (2000) Kainic acidinduced seizures produce necrotic, not apoptotic, neurons with internucleosomal DNA cleavage: implications for programmed cell death mechanisms. Neuroscience 98, 41-53   DOI   ScienceOn
30 Lei, M., Brown, H. F., and Terrar, D. A. (2000) Modulation of delayed rectifier potassium current, iK, by isoprenaline in rabbit isolated pacemaker cells. Exp. Physiol. 85, 27-35   DOI   ScienceOn
31 Ikonomidou, C., Bittigau, P., Ishimaru, M. J., Wozniak, D. F., Koch, C., et al. (2000) Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287, 1056-1060   DOI   ScienceOn
32 Suzdak, P. D., Schwartz, R. D., Skolnick, P., and Paul, S. M. (1986) Ethanol stimulates gamma-aminobutyric acid receptor- mediated chloride transport in rat brain synaptoneurosomes. Proc. Natl. Acad. Sci. USA 83, 4071-4075
33 Streissguth, A. P., Landesman-Dwyer, S., Martin, J. C., and Smith, D. W. (1980) Teratogenic effects of alcohol in humans and laboratory animals. Science 209, 353-361   DOI
34 Hu, X. J. and Ticku, M. K. (1995) Chronic ethanol treatment upregulates the NMDA receptor function and binding in mammalian cortical neurons. Brain Res. Mol. Brain Res. 30, 347-356   DOI   ScienceOn
35 Mihic, S. J., Ye, Q., Wick, M. J., Koltchine, V. V., Krasowski, M. D., et al. (1997) Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature 389, 385-389   DOI   ScienceOn
36 Archibald, S. L., Fennema-Notestine, C., Gamst, A., Riley, E. P., Mattson, S. N., et al. (2001) Brain dysmorphology in individuals with severe prenatal alcohol exposure. Dev. Med. Child Neurol. 43, 148-154   DOI
37 Babcock, A. M., Liu, H., Paden, C. M., Churn, S. B., and Pittman, A. J. (1999) In vivo glutamate neurotoxicity is associated with reductions in calcium/calmodulin-dependent protein kinase II immunoreactivity. J. Neurosci. Res. 56, 36-43   DOI   ScienceOn
38 Nutt, D, J. (1996) Addiction: brain mechanisms and their treatment implications. Lancet 347, 31-36   DOI   ScienceOn
39 Wafford, K. A., Burnett, D. M., Leidenheimer, N. J., Burt, D. R., Wang, J. B., et al. (1991) Ethanol sensitivity of the GABAA receptor expressed in Xenopus oocytes requires 8 amino acids contained in the gamma 2L subunit. Neuron 7, 27-33   DOI   ScienceOn
40 Harris, R. A. (1999) Ethanol actions on multiple ion channels: which are important? Alcohol Clin. Exp. Res. 23, 1563-1570