Nicotine-induced alterations in the expression of nicotinic receptors in primary cultures from human prenatal brain

The nicotinic receptor proteins and gene transcripts for the different nico tinic receptor subunits exist in human prenatal brain already at 4-5 weeks of gestation. The early presence of nicotinic receptors suggests an importa nt role for these receptors in modulating dendritic outgrowth, establishmen t of neuronal connections and synaptogenesis during development. When measu rements of nicotinic receptors using [H-3]epibatidine (labelling both the a lpha3 and alpha4 subtype) and [H-3]cytisine (labelling the a4 subtype) were performed in intact cells from the cortex, subcortical forebrain and mesen cephalon (7.5-11 weeks of gestation), the highest specific binding for both ligands was detected in cells from mesencephalon, followed by subcortical forebrain and cortex. The effects of nicotine exposure were studied in prim ary cultures of prenatal brain (7.5-11 weeks of gestation). Treatment with nicotine (1-100 muM) for 3 days significantly increased the specific bindin g of [H-3]epibatidine and [H-3]cytisine in cortical cells but not in cells from subcortical forebrain and mesencephalon brain regions indicating regio n-specific differences in the sensitivity to nicotine exposure. Relative qu antification of mRNA showed that the expression of the nicotinic receptor s ubunits alpha3 and alpha7, but not alpha4, was increased in cortical cells after nicotine treatment. These findings support the assumption of a potential risk of disturbance in the functional role of nicotinic receptors during brain development as a c onsequence of maternal smoking during pregnancy. (C) 2001 IBRO. Published b y Elsevier Science Ltd. All rights reserved.