title: Ethanol induces cell death by activating caspase-3 in the rat cerebral cortex.
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+/-16.4 mg/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.
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, Health Science Institute, Gyeongsang National University, Jinju.
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Han
authors.forename: Yeon
authors.initials: Y
authors.lastname: Joo
authors.forename: Yoon Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Young Ki
authors.initials: YK
authors.lastname: Lee
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
mesh_terms: D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000431:Ethanol; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases