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Priming of cultured neurons with sabeluzole results in long‐lasting inhibition of neurotoxin‐induced tau expression and cell death
Author(s) -
Uberti Daniela,
Rizzini Claudia,
Galli Paola,
Pizzi Marina,
Grilli Mariagrazia,
Lesage Anne,
Spano Pierfranco,
Memo Maurizio
Publication year - 1997
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199706)26:2<95::aid-syn1>3.0.co;2-8
Subject(s) - neuroprotection , glutamate receptor , excitotoxicity , neurotoxicity , neurotoxin , programmed cell death , tau protein , hippocampal formation , glutamate decarboxylase , microbiology and biotechnology , nmda receptor , cell culture , neurodegeneration , pharmacology , neuroscience , biology , apoptosis , chemistry , medicine , biochemistry , toxicity , alzheimer's disease , disease , receptor , genetics , enzyme
Sabeluzole was described to have antiischemic, antiepileptic, and cognitive‐enhancing properties, and is currently under development for Alzheimer's disease. Recently, it was reported that repeated treatments with sabeluzole protect cultured rat hippocampal neurons against NMDA‐and glutamate‐induced neurotoxicity. We evaluated the possibility that sabeluzole elicits neuroprotection by acting, either directly or indirectly, on tau proteins. We found that repeated treatments during development of primary cultures of cerebellar granule cells with nanomolar concentrations of sabeluzole resulted in mature cells that were resistant to the excitotoxicity induced by glutamate. Also, sabeluzole treatment specifically prevented the glutamate‐induced increase of tau expression without modifying the basal pattern of expression of tau proteins, as shown by measurement of mRNA and protein levels. In human neuroblastoma cell line SH‐SY5Y, differentiated by treatment with retinoic acid, doxorubicin increased tau immunoreactivity, and later induced cell death. Both effects were prevented by sabeluzole. Our data indicate that increased tau expression is a common response to different types of cells to neurotoxic agents, and that sabeluzole‐induced neuroprotection is functionally associated with the prevention of the injury‐mediated increase of tau expression. Synapse 26:95–103, 1997. © 1997 Wiley‐Liss, Inc.