Jpn. J. Pharmacol. 82 (4), 301-306 (2000)

Evaluation of Neurotoxicity of Alzheimer's Amyloid b Protein (b42)
in Cultured Hippocampal Cells and Its Prevention by Propentofylline

Yoshiki Koriyama, Matsumi Yamazaki, Kenzo Chiba and Tetsuro Mohri

Department of Biodynamics, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Ishikawa 920-1181, Japan

Abstract: Neurotoxicity of b42 (20╩mM) in cultured rat hippocampal neurons was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release methods as quantitative assays of cell death, and both methods indicated that propentofylline (PPF) had the ability to protect the neurons against the toxicity, although these two assay methods revealed different mechanisms for the toxic effect of b42. Promotion of the active exocytotic system of the cells was suggested after treatment with b42 in the MTT assay and in determination of 9-aminoacridine (AA) excretion from the preloaded cells after 24-h treatment with b42. The promotion of AA exocytosis was blocked by the addition of PPF (20╩mg/ml). The preventive effect of PPF on the neurotoxicity of b42 has been proposed to be caused by elevation of the intracellular level of cAMP as a result of depression of the hydrolytic activity of cells.

Keywords: b-Amyloid protein, Hippocampal neuron, Propentofylline, Exocytosis, cAMP

Copyrightę The Japanese Pharmacological Society 2000

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