Nicotine affects the expression of brain-derived neurotrophic factor mRNA and protein in the hippocampus of hypoxic newborn piglets.
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.
Andresen
Jannicke Hanne
JH
Department of Pediatric Research, Institute of Surgical Research, Medical Faculty, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway. jannickea@adhb.govt.nz
Løberg
Else Marit
EM
Wright
Marianne
M
Goverud
Ingeborg Løstegaard
IL
Stray-Pedersen
Babill
B
Saugstad
Ola Didrik
OD
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
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