Ethanol selectively interferes with the trophic action of NMDA and carbachol on cultured cerebellar granule neurons undergoing apoptosis

Anna F. Castoldi, Sergio Barni, Giovanna Randine, Lucio G. Costa, Luigi Manzo

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Exposure of mature rat cerebellar granule neurons to non-depolarizing conditions (5 mM K+) for 24 h resulted in the onset of apoptosis. NMDA, forskolin, carbachol and GABA attenuated low K+-induced toxicity, although to a different extent, with NMDA and GABA being the most effective agents. When cells were co-exposed for 24 h to ethanol, the survival promoting action of NMDA and carbachol, but not that of forskolin and GABA, was attenuated. By contrast, a 24 h cell pre-treatment with ethanol, followed by its removal prior to K+ deprivation, was ineffective towards the neurotrophic action of NMDA and carbachol. The concomitant presence of alcohol and neurotrophic factors was not required for the pro-apoptotic effect of ethanol to be manifest after a long-term alcohol exposure: inhibition of NMDA- and carbachol-mediated neurotrophism was still observed when cells were pre- exposed for 72 h to alcohol in depolarizing conditions, prior to the challenge with 5 mM K+-containing medium and the test compounds in the absence of ethanol. The present study shows that ethanol promotes apoptotic cell death of cultured cerebellar neurons by selectively inhibiting the neurotrophic effect of NMDA and carbachol, and suggests that alcohol may cause permanent changes in the control mechanisms of apoptosis: this finding may have significant implications for the in vivo toxicity of prenatal ethanol exposure on the developing cerebellum.

Original languageEnglish
Pages (from-to)279-289
Number of pages11
JournalDevelopmental Brain Research
Volume111
Issue number2
DOIs
Publication statusPublished - Dec 7 1998

Fingerprint

Carbachol
N-Methylaspartate
Ethanol
Apoptosis
Neurons
Alcohols
gamma-Aminobutyric Acid
Colforsin
Nerve Growth Factors
Cerebellum
Cell Death

Keywords

  • Apoptosis
  • Carbachol
  • Cerebellar granule cells
  • Ethanol
  • GABA
  • NMDA

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

Ethanol selectively interferes with the trophic action of NMDA and carbachol on cultured cerebellar granule neurons undergoing apoptosis. / Castoldi, Anna F.; Barni, Sergio; Randine, Giovanna; Costa, Lucio G.; Manzo, Luigi.

In: Developmental Brain Research, Vol. 111, No. 2, 07.12.1998, p. 279-289.

Research output: Contribution to journalArticle

Castoldi, Anna F. ; Barni, Sergio ; Randine, Giovanna ; Costa, Lucio G. ; Manzo, Luigi. / Ethanol selectively interferes with the trophic action of NMDA and carbachol on cultured cerebellar granule neurons undergoing apoptosis. In: Developmental Brain Research. 1998 ; Vol. 111, No. 2. pp. 279-289.
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