Smoking during early pregnancy affects the expression pattern of both nicotinic and muscarinic acetylcholine receptors in human first trimester brainstem and cerebellum.
Prenatal nicotine exposure is associated with an increased risk of complications during pregnancy and childhood. In this study the expression of nicotinic and muscarinic acetylcholine receptors in first trimester pons, medulla oblongata and cerebellum from abortus (5-12 weeks of gestation) of smoking and nonsmoking women was compared. A significant age-related increase in binding of nicotinic receptor subtype alpha4 was found in both pons and cerebellum only in fetal tissue from non-smoking women, while a similar increase was observed in medulla oblongata from fetuses exposed to smoking. A significant age-related increase in binding of muscarinic receptor subtype m2 was observed in pons from abortus of smoking compared with non-smoking women. The gene expression pattern of both alpha4 and alpha7 nicotinic receptor subunits was changed after smoking in all three regions investigated. Smoking also changed the expression of m1 and 2 muscarinic receptor mRNA in pons, m1 mRNA in cerebellum and the m3 mRNA in medulla oblongata. The findings indicate that early prenatal nicotine exposure affects the normal developmental pattern of the cholinergic system in human fetal brain.
Falk
L
L
Karolinska Institutet, Neurotec Department, Division of Molecular Neuropharmacology, Karolinska University Hospital Huddinge, S-141 86, Stockholm, Sweden. lena.falk@neurotec.ki.se
Nordberg
A
A
Seiger
A
A
Kjaeldgaard
A
A
Hellström-Lindahl
E
E
D000470:Alkaloids / Q000494:pharmacology; D001392:Azocines / Q000494:pharmacology; D001933:Brain Stem / Q000033:anatomy & histology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011807:Quinolizines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012907:Smoking / Q000009:adverse effects*; D014316:Tritium / Q000494:pharmacology; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D009538:Nicotine; D018722:Nicotinic Agonists; D010890:Pirenzepine; D011807:Quinolizines; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D014316:Tritium; C065959:AFDX 384; C004712:cytisine; D000093843:Quinolizidine Alkaloids