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)
  • Received : 2005.03.08
  • Accepted : 2005.06.21
  • Published : 2005.10.31

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

Acknowledgement

Supported by : Ministry of Education

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