Caffeine-induced neuronal death in neonatal rat brain and cortical cell cultures.
We examined the potential neurotoxicity of caffeine and. Intraperitoneal administration of caffeine (50 mg/kg, 3 times a day) produced neuronal death in various brain areas of neonatal rats 24 h later. Caffeine at doses > 300 microM was also neurotoxic in murine cortical cell cultures. Caffeine-induced neuronal death was accompanied by cell body shrinkage and attenuated by anti-apoptotic drugs including cycloheximide, high potassium, and growth factors. Two necrotic pathways, excitotoxicity and oxidative stress, did not mediate caffeine neurotoxicity. The pro-apoptotic protease caspase-3 was activated to mediate neuronal death following exposure to caffeine. The present findings suggest that caffeine may cause caspase-3-dependent neuronal cell apoptosis in neonatal rat as well as.
Kang
Sang Hwan
SH
Department of Neuroscience, Ajou University School of Medicine, San 5, Wonchon-dong, Paldal-gu, Suwon, Kyungki-do 442-749, Korea.
Lee
Young Ae
YA
Won
Seok Joon
SJ
Rhee
Ki-Hyeong
KH
Gwag
Byoung Joo
BJ
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002110:Caffeine / Q000633:toxicity*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects* / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus; D006133:Growth Substances / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D006133:Growth Substances; D009498:Neurotoxins; D002110:Caffeine; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D011188:Potassium