title: N-methyl-D-aspartate receptor 1 changes in the piglet braintem after nicotine and/or intermittent hypercapnic-hypoxia.
abstract: Prone sleeping and cigarette smoke exposure are two major risk factors for the sudden infant death syndrome (SIDS). Utilizing piglet models of early postnatal nicotine and/or intermittent hypercapnic-hypoxia (IHH) exposure, we tested the hypothesis that these exposures, separately or combined, increase N-methyl-D-aspartate (NMDA) receptor 1 (NR1) expression in the brainstem medulla. We also tested for gender-specific effects. Three piglet exposure groups were compared against 14 controls; 1, nicotine [n = 14], 2, IHH [n = 10], and 3, nicotine+IHH [n = 14], with equal gender proportions in each group. Non-radioactive in situ hybridization and immunohistochemistry were performed for NR1 mRNA and protein expression, respectively, and were quantified in seven nuclei of the brainstem medulla. NR1 mRNA was significantly increased in the gracile and inferior olivary nucleus (ION) after nicotine exposure, in five of seven nuclei after IHH exposure, and in three of seven nuclei after nicotine+IHH. The increased mRNA changes were accompanied by increased protein only in the ION after IHH and nicotine+IHH (P = 0.019, and P = 0.008 respectively). By gender, control females had greater NR1 mRNA than males in the dorsal motor nucleus of vagus (P = 0.05) and for protein in the ION (P = 0.02). This gender difference was maintained after nicotine exposure in the ION with additional gender differences observed including greater mRNA in the cuneate nucleus (P = 0.04) and nucleus of the spinal trigeminal tract (P = 0.03) of males compared with females. Overall, more changes occurred at the mRNA level than protein, and IHH exposure induced more changes than nicotine or nicotine+IHH exposures. Together, these findings suggest that hypercapnic-hypoxic exposures (modeling prone sleeping or sleep apnea) are more likely to induce NMDA receptor changes in the developing brainstem than nicotine exposure alone.
authors.affiliation: Department of Anatomy and Histology, University of Sydney, NSW 2006, Sydney, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Fanous
authors.forename: R
authors.initials: R
authors.lastname: Machaalani
authors.forename: K A
authors.initials: KA
authors.lastname: Waters
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006935:Hypercapnia / Q000097:blood / Q000473:pathology*; D000860:Hypoxia / Q000097:blood / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009538:Nicotine / Q000097:blood / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012737:Sex Factors; D013552:Swine; D013556:Swine, Miniature
chemical_list: C409466:NR1 NMDA receptor; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D009538:Nicotine