Nicotine-induced alterations in the expression of nicotinic receptors in primary cultures from human prenatal brain
Section snippets
Brain tissues
First trimester brain tissue from humans (7.5–11 weeks of gestation) was obtained following routine abortions by vacuum aspiration after the pregnant women’s consent. Brain regions were dissected under sterile conditions in Ringer’s solution within 1–1.5 h of surgical tissue retrieval and separated on the basis of their morphological appearance according to Seiger (1989). Subcortical forebrain is defined as all CNS tissue rostral to mesencephalon, with the exception of the neocortical anlage,
[3H]Epibatidine and [3H]cytisine binding to intact primary neuronal cells from human fetal brain
Specific binding of [3H]epibatidine and [3H]cytisine to intact primary cell cultures from cortex, subcortical forebrain and mesencephalon of 7.5–11 weeks gestational age was measured using a single concentration (0.2 and 2.0 nM, respectively). The specific binding of both ligands was highest in cultured cells from the mesencephalon (approximately 30 fmol/mg protein) followed by the subcortical forebrain (15–18 fmol/mg protein) and cortical cells (11 fmol/mg protein) (Table 1). In saturation
Discussion
Developmental animal models exposing the fetus to nicotine by itself and without involvement of other confounding factors of smoking have demonstrated nicotine being neuroteratogenic (Slotkin, 1998). Direct specific actions of nicotine on the developing brain are quite plausible during the major part of prenatal life, since the nAChRs are already detectable in brain and spinal cord at 4–5 weeks gestational age (Hellström-Lindahl et al., 1998). It is believed that nicotine exposure of prenatal
Conclusion
This study shows that it is possible to detect and characterize nAChRs in primary cell cultures from human fetal brain and that nicotine exposure to these cells at relevant concentrations up-regulates nAChR binding sites and increases the expression of their transcripts. These findings suggest that a potential risk exists that the normal functional role of nAChRs during brain development might be disturbed as a consequence of maternal smoking or treatment with transdermal nicotine patches
Acknowledgements
This work was supported by grants from the Swedish Medical Research Council (Project numbers 13426, 05817 and 06555), Council for Medical Tobacco Research, Swedish Match, Magnus Bergwall Foundation, Alcohol Research Council for the Swedish Alcohol Retailing Monopoly, Stiftelsen Gamla Tjänarinnor, Åke Wiberg’s Foundation and KI Foundations.
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