title: Nicotine affects the expression of brain-derived neurotrophic factor mRNA and protein in the hippocampus of hypoxic newborn piglets.
abstract: Brain-derived neurotrophic factor (BDNF) is highly expressed in the developing brain. It has anti-apoptotic abilities, and protects the neonatal brain. In experimental settings in adult animals, pre-treatment with nicotine has shown increased BDNF levels, indicating a possible contribution to nicotine's anti-apoptotic effect. Apoptosis contributes to the development of brain damage in perinatal asphyxia. We examined the effects of nicotine on apoptosis-inducing factor (AIF), caspase-3 and BDNF in the hippocampus of a neonatal piglet model of global hypoxia. Forty-one anesthetized newborn piglets were randomized to one of four groups receiving different infusions after hypoxia (1) nicotine 130 microg/kg/h, 2) 260 microg/kg/h, 3) adrenaline, and 4) saline, all 2.6 mL/kg/h. Four hours after hypoxia they were euthanized. The left hemisphere/hippocampus was examined by histopathology and immunohistochemistry; the right hippocampus was analyzed using real time PCR. There was a significantly higher expression of BDNF mRNA and protein in the animals treated with nicotine 130 microg/kg/h vs. the saline treated group (mRNA P=0.038; protein P=0.009). There were no differences regarding AIF or caspase-3. We conclude that nicotine (130 microg/kg/h), infused over 1 h after global hypoxia in neonatal piglets, increases levels of both BDNF mRNA and protein in the hippocampus. This might imply neuroprotective effects of nicotine in asphyxiated neonates.
authors.affiliation: Department of Pediatric Research, Institute of Surgical Research, Medical Faculty, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway. jannickea@adhb.govt.nz
authors.forename: Jannicke Hanne
authors.initials: JH
authors.lastname: Andresen
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.forename: Marianne
authors.initials: M
authors.lastname: Wright
authors.forename: Ingeborg Løstegaard
authors.initials: IL
authors.lastname: Goverud
authors.forename: Babill
authors.initials: B
authors.lastname: Stray-Pedersen
authors.forename: Ola Didrik
authors.initials: OD
authors.lastname: Saugstad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051033:Apoptosis Inducing Factor / Q000235:genetics; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D013552:Swine; D014018:Tissue Distribution
chemical_list: D051033:Apoptosis Inducing Factor; D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D009538:Nicotine; D053148:Caspase 3