Neonatal alcohol exposure reduces NMDA induced Ca2+ signaling in developing cerebellar granule neurons

D. L. Gruol, A. E. Ryabinin, K. L. Parsons, M. Cole, M. C. Wilson, Z. Qiu

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Glutamatergic neurotransmission through NMDA receptors is critical for both neurogenesis and mature function of the central nervous system (CNS), and is thought to be one target for developmentally-induced damage by alcohol to brain function. In the current study we examined Ca2+ signaling linked to NMDA receptor activation as a potential site for alcohol's detrimental effects on the developing nervous system. We compared Ca2+ signals to NMDA in granule neurons cultured from cerebella of rat neonates exposed to alcohol (ethanol) during development with responses to NMDA recorded in separated control groups. Alcohol exposure was by the vapor chamber method on postnatal days 4-7. An intermittent exposure paradigm was used where the pups were exposed to alcohol vapor for 2.5 h/day to produce peak BALs of ~ 320 mg%. Control pups were placed in an alcohol-free chamber for a similar time period or remained with their mother. After culture under alcohol-free conditions for up to 9 days, Ca2+ signaling in response to NMDA was measured using fura-2 Ca2+ imaging. Results show that the peak amplitude of the Ca2+ signal to NMDA was significantly smaller in cultured granule neurons obtained from alcohol-treated pups compared to granule neurons from control pups. In contrast, the Ca2+ signal to K+ depolarization was not depressed by the alcohol treatment. Resting Ca2+ levels were also altered by the alcohol treatment. These results show that intermittent alcohol exposure during development in vivo can induce long-term changes in CNS neurons that affect the Ca2+ signaling pathway linked to NMDA receptors and resting Ca2+ levels. Such changes could play an important role in the CNS dysfunction associated with alcohol exposure during CNS development.

Original languageEnglish (US)
Pages (from-to)12-20
Number of pages9
JournalBrain research
Volume793
Issue number1-2
DOIs
StatePublished - May 18 1998

Keywords

  • CNS neuron
  • Development
  • Ethanol
  • Glutamate receptor
  • Intracellular calcium

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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