Minocycline recovers MTT-formazan exocytosis impaired by amyloid beta peptide.
Minocycline, a tetracycline antibiotic, has been reported to exert beneficial effects in models of Alzheimer's disease (AD). To characterize the mechanisms underlying the putative minocycline-related neuroprotection, we studied its effect in an in vitro model of AD. Primary hippocampal cultures were treated with β-amyloid peptide (Aβ) and cell viability was assessed by standard MTT-assay. Incubation with 10 μM Aβ for 24 h significantly inhibits cellular MTT-reduction without inducing morphological signs of enhanced cell death or increase in release of lactate dehydrogenase. This indicates that cell viability was not affected. The inhibition of MTT-reduction by Aβ was due to an acceleration of MTT-formazan exocytosis. Intriguingly, the Aβ-triggered increase in MTT-formazan exocytosis was abolished by co-treatment with minocycline. In vehicle-treated cells minocycline had no effect on formazan exocytosis. This hitherto unrecognized property of minocycline has to be noticed in the elucidation of the underlying mechanism of this promising neuroprotectant.
Kreutzmann
Peter
P
Institute of Medical Neurobiology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, Magdeburg, Germany. peter.kreutzmann@med.ovgu.de
Wolf
Gerald
G
Kupsch
Kathleen
K
D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D005089:Exocytosis / Q000187:drug effects*; D005562:Formazans / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000900:Anti-Bacterial Agents; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D008911:Minocycline
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