BAPTA-AM and ethanol protect cerebellar granule neurons from the destructive effect of the weaver gene

Päivi Liesi, Jerry M. Wright, Victor Krauthamer

Research output: Contribution to journalArticle

Abstract

The mechanisms by which the weaver gene (Reeves et al., 1989; Patil et al., 1995) inhibits neurite extension and/or induces death of the granule neurons in homozygous weaver mouse cerebellum are not presently understood. Here we show that BAPTA-AM and ethanol, which either reduce cytosolic levels of free calcium or prevent calcium entry, promote neurite outgrowth of the weaver neurons similar to the L-type calcium channel blocker verapamil (Liesi and Wright, 1996). Importantly, BAPTA-AM, ethanol, and verapamil not only restore neurite outgrowth of the weaver neurons but adjust their depolarized resting membrane potentials to the levels of normal neurons. These results indicate that calcium-dependent mechanisms mediate the action of the weaver gene and that the weaver neurons can be normalized by blocking this calcium effect. We further report that BAPTA-AM and verapamil also have a neuroprotective effect on normal neurons exposed to high concentrations of ethanol. We suggest that verapamil should be evaluated as a drug for treatment of alcohol-induced brain damage and neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)571-579
Number of pages9
JournalJournal of neuroscience research
Volume48
Issue number6
DOIs
StatePublished - Jun 15 1997

Keywords

  • BAPTA-AM
  • Calcium
  • Cerebellum
  • Ethanol
  • Granule neurons
  • Rescue
  • Weaver

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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