Effect of nicotine on cerebellar granule neuron development
Open accessAbstract
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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- Authors
- Opanashuk, L. A., Pauly, J. R., & Hauser, K. F.
- Affiliations
- University of Kentucky (US)
- ORCID
- Hauser, Kurt F.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2001-01
- Volume
- 13
- Issue
- 1
- Pages
- 48-56
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC4823140
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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