Effect of nicotine on cerebellar granule neuron development

Lisa A. Opanashuk, James R. Pauly, Kurt F. Hauser

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

To assess the role of nicotinic cholinergic receptors (nAChR) on neuronal maturation, nAChR expression and the direct effects of nAChR activation were examined in cerebellar external granular layer (EGL) precursors isolated in vitro. Treatment of EGL neuroblasts with nicotine elicited a concentration-dependent increase in DNA content and synthesis, implying an increase in cell numbers. Pretreatment of cultures with the nAChR antagonist dihydro-β-erythroidine (DHBE) attenuated nicotine-induced changes in DNA abundance and synthesis. Furthermore, chronic nicotine treatment for 4-7 days promoted EGL cell survival. Epibatidine but not cytisine stimulated granule neuroblast DNA synthesis and survival. Survival effects mediated by nicotine and epibatidine were attenuated by pretreating cultures with DHBE. Immunocytochemical analysis revealed that EGL neurons possessed α3, but not α4, nAChR immunoreactivity. Quantitative autoradiography was used to determine which nAChRs are present during the period of granule cell neurogenesis in vivo. On postnatal day 5, the EGL was intensely labelled by [3H] epibatidine but virtually devoid of [3H]-A85380 binding, suggesting that a high concentration of α3 AChRs is present in granule neuroblasts. The pharmacology of [3H]-epibatidine displacement from EGL neurons also suggested an imeraction wire me α3nAChR subunits. Together these data provide novel evidence that the activation of nAChRs directly affect the development of primary cerebellar neuroblasts and further suggest that the effects are mediated through the α3-nAChR subtype.

Original languageEnglish
Pages (from-to)48-56
Number of pages9
JournalEuropean Journal of Neuroscience
Volume13
Issue number1
DOIs
StatePublished - 2001

Keywords

  • Cerebellar development
  • Neuroblast proliferation
  • Neurogenesis
  • Nicotinic receptors
  • Programmed cell death
  • α3 nicotinic receptor subunits

ASJC Scopus subject areas

  • Neuroscience (all)

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