Nicotine Evokes Cell Death in Embryonic Rat Brain during Neurulation
Abstract
Maternal cigarette smoking during pregnancy represents the most prevalent exposure to a suspected neuroteratogen, nicotine. Although animal models have demonstrated brain cell loss and synaptic abnormalities after prenatal nicotine exposure, the multiple effects of nicotine on the maternal-fetal unit make it difficult to prove that nicotine itself is a neuroteratogen. In the current study, whole rat embryo culture was used to study the effects of nicotine at the neural tube stage of development. Beginning on embryonic day 9.5, embryos were exposed to 1, 10 or 100 microM nicotine. After 48 hr, embryos were examined for dysmorphogenesis and were then processed for light microscopic examination of the neuroepithelium. Examination of the forebrain, midbrain and hindbrain regions revealed extensive cytotoxicity, evidenced by cytoplasmic vacuolation, enlargement of intercellular spaces and a sharply increased incidence of pyknotic/apoptotic cells. These alterations were evident in the absence of generalized dysmorphogenesis and were detectable even at the lowest concentration of nicotine. At the highest concentration, abnormalities were present in the majority of cells. Superimposed on cell damage, we found an increase in mitotic figures. Although enhanced mitosis could represent partial compensation for cell loss, the regional selectivity and concentration dependence of the mitogenic effect differed significantly from that of cell death, suggesting separable mechanisms. The present results support the view that nicotine is a neuroteratogen, specifically targeting brain development at concentrations below the threshold for dysmorphogenesis.
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First-trimester nicotine exposure can disrupt brain development at cellular and structural levels.
“Even first-trimester exposure can induce disruption of brain development at both cellular and structural levels.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [51]
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“…acting as trophic substances, typically elicit biphasic developmental actions, promoting cell division at early stages but fostering the switch from replication to differentiation later in development (Buznikov et al., 1970; Lauder, 1985; Slotkin et al., 1987c, 1988a,b; Whitaker-Azmitia, 1991).”
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- Authors
- Roy, T. S., Andrews, J. E., Seidler, F. J., & Slotkin, T. A.
- Affiliations
- All India Institute of Medical Sciences (IN)
- ORCID
- Roy, T.S.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 287
- Issue
- 3
- Pages
- 1136-1144
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2303404807
- Cited by
- 147
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 5 · 2021: 3 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 6 · 2014: 8 · 2013: 8 · 2012: 1
- FWCI
- 5.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- nicotine, prenatal nicotine exposure, maternal smoking, neurulation, neural tube, embryonic brain development, neuronal cell death, apoptosis, mitosis, neuroepithelium, rat embryo culture
- MeSH terms
- Animals, Brain, Embryo, Mammalian, Female, Gestational Age, Mitosis, Neural Crest, Nicotine, Organ Culture Techniques, Receptors, Nicotinic, Teratogens, Cell Death, Apoptosis, Rats
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