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Caffeine-induced neuronal death in neonatal rat brain and cortical cell cultures

Kang, Sang Hwan1 3; Ae Lee, Young1 3; Won, Seok Joon1 3; Rhee, Ki-Hyeong4; Gwag, Byoung Joo1 2 3 CA

Neuropharmacology And Neurotoxicology

We examined the potential neurotoxicity of caffeine in vivo and in vitro. 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 μM 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 in vitro.

Departments of1Neuroscience


3Center for the Interventional Therapy of Stroke and Alzheimer's Disease, Ajou University School of Medicine, San 5, Wonchon-dong, Paldal-gu, Suwon, Kyungki-do 442-749

4Department of Biological Science, Kongju National University, Kongju 314-701, Korea

CA,1Corresponding Author and Address:

Received 12 August 2002; accepted 18 August 2002

© 2002 Lippincott Williams & Wilkins, Inc.