title: Brain-derived neurotrophic factor (BDNF) and TrkB in the piglet brainstem after post-natal nicotine and intermittent hypercapnic hypoxia.
abstract: Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play a significant role in the regulation of cell growth, survival and death during central nervous system development. The expression of BDNF and TrkB is affected by noxious insults. Two insults during the early post-natal period that are of interest to our laboratory are exposure to nicotine and to intermittent hypercapnic hypoxia (IHH). Piglet models were used to mimic the conditions associated with the risk factors for the sudden infant death syndrome (SIDS) including post-natal cigarette smoke exposure (nicotine model) and prone sleeping where the infant is subjected to re-breathing of expired gases (IHH model). We aimed to determine the effects of nicotine and IHH, alone or in combination, on pro- and rhBDNF and TrkB expression in the developing piglet brainstem. Four piglet groups were studied, with equal gender ratios in each: control (n=14), nicotine (n=14), IHH (n=10) and nic+IHH (n=14). Applying immunohistochemistry, and studying six nuclei of the caudal medulla, we found that compared to controls, TrkB was the only protein significantly decreased after nicotine and nic+IHH exposure regardless of gender. For pro-BDNF and rhBDNF however, observed changes were more evident in males than females exposed to nicotine and nic+IHH. The implications of these findings are that a prior nicotine exposure makes the developing brainstem susceptible to greater changes in the neurotrophic effects of BDNF and its receptor TrkB in the face of a hypoxic insult, and that the effects are greater in males than females.
authors.affiliation: Department of Paediatrics and Child Health, The University of Sydney, and The Children's Hospital, Westmead Sydney, NSW 2006, Australia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Tang
authors.forename: Rita
authors.initials: R
authors.lastname: Machaalani
authors.forename: Karen A
authors.initials: KA
authors.lastname: Waters
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006935:Hypercapnia / Q000523:psychology*; D000860:Hypoxia / Q000523:psychology*; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000254:growth & development; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D020813:Receptor, trkB / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012727:Sex Characteristics; D013552:Swine
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018722:Nicotinic Agonists; D011994:Recombinant Proteins; D009538:Nicotine; D020813:Receptor, trkB