Cited by 51Nicotinic Acetylcholine Receptors StudyNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

Effect of nicotine on cerebellar granule neuron development

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Opanashuk, Lisa A., Pauly, James R., Hauser, Kurt F.·2001·European Journal of Neuroscience

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-beta-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 alpha3, but not alpha4, 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 alpha3 AChRs is present in granule neuroblasts. The pharmacology of [3H]-epibatidine displacement from EGL neurons also suggested an interaction with the alpha3-nAChR 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 alpha3-nAChR subtype.

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Crossref · 10.1111/j.1460-9568.2001.01359.x

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Research works printed but not linked: 3

  1. Collins AC, Marks MJ. Are nicotinic receptors activated or inhibited following chronic nicotine treatment? Drug Dev Res. 1996;38:231–242. [Google Scholar]
  2. Pauly JR, Anderson DJ, Sullivan JP. Autoradiographic comparison of [3H]-A85380, [3H]-epibatidine and [3H]-cytisine binding in rat and mouse brain. Soc Neurosci Abst. 1996;22:1264. [Google Scholar]
  3. Tao Y, Black IB, DiCicco-Bloom E. In vivo neurogenesis is inhibited by neutralizing antibodies to basic fibroblast growth factor. J Neurobiol. 1997;33:289–296. [PubMed] [Google Scholar]

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Authors
Opanashuk, L. A., Pauly, J. R., & Hauser, K. F.
Affiliations
University of Kentucky (US)
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2001-01
Volume
13
Issue
1
Pages
48-56
ISSN
  • 0953-816X (ISSN-L)
  • 1460-9568
OpenAlex
W2026940418
Cited by
51
References
77
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 3 · 2012: 1
FWCI
2.21
Type
journal article
Language
en
Open access
Locations
  • European Journal of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r29da008443-06)
  • National Institute on Drug Abuse (R01DA006204, DA 08443, DA06204)
  • National Institute of Neurological Disorders and Stroke (F32NS010007, NS 10007)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
nicotine, nicotinic acetylcholine receptors, cerebellar granule cells, external granular layer, DNA synthesis, cell survival, epibatidine, dihydro-beta-erythroidine, receptor subtypes, neurogenesis
MeSH terms
Quinolizidine Alkaloids, Alkaloids, Animals, Azocines, Cell Survival, Cells, Cultured, Cerebellum, DNA, Mice, Inbred ICR, Neurons, Nicotine, Pyridines, Quinolizines, Receptors, Cholinergic, Stem Cells, Cellular Senescence, Nicotinic Agonists, Bridged Bicyclo Compounds, Heterocyclic, Protein Isoforms, Mice

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