Open AccessEvaluation of Neurotoxicity of Alzheimer’s Amyloid β Protein (β42) in Cultured Hippocampal Cells and Its Prevention by Propentofylline
Author(s) -
Yoshiki Koriyama,
Matsumi Yamazaki,
Kenzo Chiba,
Tetsuro Mohri
Publication year - 2000
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.82.301
Subject(s) - neurotoxicity , lactate dehydrogenase , chemistry , pharmacology , hippocampal formation , intracellular , biochemistry , toxicity , microbiology and biotechnology , biology , medicine , enzyme , organic chemistry
Neurotoxicity of beta42 (20 microM) 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 beta42. Promotion of the active exocytotic system of the cells was suggested after treatment with beta42 in the MTT assay and in determination of 9-aminoacridine (AA) excretion from the preloaded cells after 24-h treatment with beta42. The promotion of AA exocytosis was blocked by the addition of PPF (20 microg/ml). The preventive effect of PPF on the neurotoxicity of beta42 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.