Priming of cultured neurons with sabeluzole results in long-lasting inhibition of neurotoxin-induced tau expression and cell death

Daniela Uberti, Claudia Rizzini, Paola Galli, Marina Pizzi, Mariagrazia Grilli, Anne Lesage, Pierfranco Spano, Maurizio Memo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)95-103
Number of pages9
JournalSynapse
Volume26
Issue number2
DOIs
Publication statusPublished - Jun 1997

Fingerprint

sabeluzole
Neurotoxins
Cell Death
Neurons
Glutamic Acid
tau Proteins
N-Methylaspartate
Tretinoin
Inhibition (Psychology)
Neuroblastoma
Anticonvulsants
Doxorubicin
Alzheimer Disease

Keywords

  • cerebellar granule cells
  • doxorubicin
  • glutamate
  • human neuroblastoma SH- SY5Y
  • PCR
  • Tau proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Priming of cultured neurons with sabeluzole results in long-lasting inhibition of neurotoxin-induced tau expression and cell death. / Uberti, Daniela; Rizzini, Claudia; Galli, Paola; Pizzi, Marina; Grilli, Mariagrazia; Lesage, Anne; Spano, Pierfranco; Memo, Maurizio.

In: Synapse, Vol. 26, No. 2, 06.1997, p. 95-103.

Research output: Contribution to journalArticle

Uberti, Daniela ; Rizzini, Claudia ; Galli, Paola ; Pizzi, Marina ; Grilli, Mariagrazia ; Lesage, Anne ; Spano, Pierfranco ; Memo, Maurizio. / Priming of cultured neurons with sabeluzole results in long-lasting inhibition of neurotoxin-induced tau expression and cell death. In: Synapse. 1997 ; Vol. 26, No. 2. pp. 95-103.
@article{cbe366348a2848c9b6658c78715d3828,
title = "Priming of cultured neurons with sabeluzole results in long-lasting inhibition of neurotoxin-induced tau expression and cell death",
abstract = "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.",
keywords = "cerebellar granule cells, doxorubicin, glutamate, human neuroblastoma SH- SY5Y, PCR, Tau proteins",
author = "Daniela Uberti and Claudia Rizzini and Paola Galli and Marina Pizzi and Mariagrazia Grilli and Anne Lesage and Pierfranco Spano and Maurizio Memo",
year = "1997",
month = "6",
doi = "10.1002/(SICI)1098-2396(199706)26:2<95::AID-SYN1>3.0.CO;2-8",
language = "English",
volume = "26",
pages = "95--103",
journal = "Synapse",
issn = "0887-4476",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Priming of cultured neurons with sabeluzole results in long-lasting inhibition of neurotoxin-induced tau expression and cell death

AU - Uberti, Daniela

AU - Rizzini, Claudia

AU - Galli, Paola

AU - Pizzi, Marina

AU - Grilli, Mariagrazia

AU - Lesage, Anne

AU - Spano, Pierfranco

AU - Memo, Maurizio

PY - 1997/6

Y1 - 1997/6

N2 - 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.

AB - 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.

KW - cerebellar granule cells

KW - doxorubicin

KW - glutamate

KW - human neuroblastoma SH- SY5Y

KW - PCR

KW - Tau proteins

UR - http://www.scopus.com/inward/record.url?scp=0030958216&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030958216&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-2396(199706)26:2<95::AID-SYN1>3.0.CO;2-8

DO - 10.1002/(SICI)1098-2396(199706)26:2<95::AID-SYN1>3.0.CO;2-8

M3 - Article

C2 - 9131769

AN - SCOPUS:0030958216

VL - 26

SP - 95

EP - 103

JO - Synapse

JF - Synapse

SN - 0887-4476

IS - 2

ER -