Ethanol induces cell death by activating caspase-3 in the rat cerebral cortex.
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.
Han
Jae Yoon
JY
Department of Anatomy and Neurobiology, College of Medicine, Health Science Institute, Gyeongsang National University, Jinju.
Joo
Yeon
Y
Kim
Yoon Sook
YS
Lee
Young Ki
YK
Kim
Hyun Joon
HJ
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
Kang
Sang Soo
SS
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
D000431:Ethanol; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases