title: Postnatal nicotine effects on the expression of nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem.
abstract: Postnatal exposure to cigarette smoke during infancy is associated with increased number of respiratory illnesses, impaired pulmonary function, and the occurrence of Sudden Infant Death Syndrome (SIDS). It is also associated with reduced cognitive functioning and attention deficits in childhood. Nicotine, the major neurotoxic component of cigarette smoke, induces its actions by binding to nicotinic acetylcholine receptors (nAChR). Using a piglet model of postnatal nicotine exposure, we studied the immunohistochemical expression of nAChR subunits α2, α3, α4, α5, α7, α9, β1 and β2 in the brainstem medulla and the hippocampus, given the role of these structures in cardiorespiratory control and cognition, respectively. We compared piglets exposed postnatally to 2mg/kg/day nicotine for 14 days (n=14: 7 males: 7 females) to controls (n=14: 7 males: 7 females). In the hippocampus, decreased expression was seen for α3 in CA1 (p=0.017), α9 in CA1 (p<0.001) and CA2 (p<0.001), β1 in CA1 (p=0.001) and CA2 (p=0.001) and β2 in CA3 (p=0.036). In the medulla, the nucleus of the spinal trigeminal tract had increased α2 and α4; vestibular nucleus increased α2 and α3, and decreased α4; hypoglossal decreased α3 and β1; dorsal motor nucleus of the vagus decreased α4 and β1. This is the first demonstration that non-classical nAChR subunits are affected by postnatal nicotine in the developing brain, and the implications are discussed.
authors.affiliation: The BOSCH Institute, NSW 2006, Australia; Department of Medicine, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia.
authors.forename: Arunnjah
authors.initials: A
authors.lastname: Vivekanandarajah
authors.affiliation: The BOSCH Institute, NSW 2006, Australia; Department of Medicine, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia; The Children's Hospital, Westmead Sydney, NSW 2145, Australia.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Waters
authors.affiliation: The BOSCH Institute, NSW 2006, Australia; Department of Medicine, Blackburn Building, DO6, University of Sydney, NSW 2006, Australia; The Children's Hospital, Westmead Sydney, NSW 2145, Australia. Electronic address: ritam@med.usyd.edu.au.
authors.forename: Rita
authors.initials: R
authors.lastname: Machaalani
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects* / Q000254:growth & development; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine
keywords: Brain; Cigarette; Immunohistochemistry; Protein; Sudden Infant Death Syndrome