title: Nicotine and brain development.
abstract: Preclinical studies, using primarily rodent models, have shown acetylcholine to have a critical role in brain maturation via activation of nicotinic acetylcholine receptors (nAChRs), a structurally diverse family of ligand-gated ion channels. nAChRs are widely expressed in fetal central nervous system, with transient upregulation in numerous brain regions during critical developmental periods. Activation of nAChRs can have varied developmental influences that are dependent on the pharmacologic properties and localization of the receptor. These include regulation of transmitter release, gene expression, neurite outgrowth, cell survival, and synapse formation and maturation. Aberrant exposure of fetal and neonatal brain to nicotine, through maternal smoking or nicotine replacement therapy (NRT), has been shown to have detrimental effects on cholinergic modulation of brain development. These include alterations in sexual differentiation of the brain, and in cell survival and synaptogenesis. Long-term alterations in the functional status and pharmacologic properties of nAChRs may also occur, which result in modifications of specific neural circuitry such as the brainstem cardiorespiratory network and sensory thalamocortical gating. Such alterations in brain structure and function may contribute to clinically characterized deficits that result from maternal smoking, such as sudden infant death syndrome and auditory-cognitive dysfunction. Although not the only constituent of tobacco smoke, there is now abundant evidence that nicotine is a neural teratogen. Thus, alternatives to NRT should be sought as tobacco cessation treatments in pregnant women.
authors.affiliation: Department of Pharmacology, University of California, Irvine, California 92697, USA. jbdwyer@uci.edu
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dwyer
authors.forename: Ron S
authors.initials: RS
authors.lastname: Broide
authors.forename: Frances M
authors.initials: FM
authors.lastname: Leslie
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development*; D003072:Cognition Disorders / Q000139:chemically induced; D005260:Female; D005731:Ganglionic Stimulants / Q000009:adverse effects*; D006801:Humans; D007859:Learning Disabilities / Q000139:chemically induced; D009538:Nicotine / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D005731:Ganglionic Stimulants; D011978:Receptors, Nicotinic; D009538:Nicotine