title: Nicotine exposure during the third trimester equivalent of human gestation: time course of effects on the central cholinergic system of rats.
abstract: Up to 22% of pregnant women smoke, which constitutes a major health concern. Nicotine, a cholinergic agonist, causes deleterious effects on brain development. However, most studies investigate its effects during rodents' gestation, which corresponds, in terms of neural development, to the first two trimesters of human gestation. Here, we focused on effects of nicotine on the brain cholinergic system during the third trimester equivalent of human gestation. From the 2nd to the 19th day of lactation, dams were exposed either to nicotine (6 mg/kg/day) or to saline via sc osmotic minipumps. Offspring were sacrificed during exposure (PN15, PN, postnatal) or at 2 days (PN21), 11 days (PN30), or 10 weeks (PN90) of withdrawal. In the cerebral cortex, midbrain, and hippocampus, we assessed nicotinic acetylcholine receptor (nAChR) binding, [(3)H]hemicholinium-3 (HC-3) binding to the high-affinity choline transporter, choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) activities. Nicotine-exposed offspring presented nAChR upregulation during exposure in all brain regions, reduced HC-3 binding during and 11 days postexposure, and increased HC-3 binding on PN90. Effects on ChAT and AChE were dependent on the brain region and restricted to the withdrawal period: There were increased activities in the midbrain on PN30. In the hippocampus, AChE as reduced on PN30, whereas, for ChAT, the decrease was followed by late-emergent increased activity. These data indicate that maternal nicotine exposure during the third trimester equivalent of human gestation promotes cholinergic system alterations in the offspring's brain. In addition, detrimental effects are observable even long after the exposure has been interrupted.
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Centro Biomédico, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-170, Brazil.
authors.forename: André Luis
authors.initials: AL
authors.lastname: Nunes-Freitas
authors.forename: Anderson
authors.initials: A
authors.lastname: Ribeiro-Carvalho
authors.forename: Carla Soares
authors.initials: CS
authors.lastname: Lima
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Dutra-Tavares
authors.forename: Alex C
authors.initials: AC
authors.lastname: Manhães
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Lisboa
authors.forename: Elaine
authors.initials: E
authors.lastname: Oliveira
authors.forename: Egberto
authors.initials: E
authors.lastname: Gaspar de Moura
authors.forename: Cláudio C
authors.initials: CC
authors.lastname: Filgueiras
authors.forename: Yael
authors.initials: Y
authors.lastname: Abreu-Villaça
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000633:toxicity*; D059329:Cholinergic Neurons; D005260:Female; D005731:Ganglionic Stimulants / Q000633:toxicity*; D005865:Gestational Age; D006801:Humans; D008431:Maternal-Fetal Exchange; D009538:Nicotine / Q000633:toxicity*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism
chemical_list: D018678:Cholinergic Agents; D005731:Ganglionic Stimulants; D011978:Receptors, Nicotinic; D009538:Nicotine; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase