title: The Alteration of Neonatal Raphe Neurons by Prenatal-Perinatal Nicotine. Meaning for Sudden Infant Death Syndrome.
abstract: Nicotine may link maternal cigarette smoking with respiratory dysfunctions in sudden infant death syndrome (SIDS). Prenatal-perinatal nicotine exposure blunts ventilatory responses to hypercapnia and reduces central respiratory chemoreception in mouse neonates at Postnatal Days 0 (P0) to P3. This suggests that raphe neurons, which are altered in SIDS and contribute to central respiratory chemoreception, may be affected by nicotine. We therefore investigated whether prenatal-perinatal nicotine exposure affects the activity, electrical properties, and chemosensitivity of raphe obscurus (ROb) neurons in mouse neonates. Osmotic minipumps, implanted subcutaneously in 5- to 7-day-pregnant CF1 mice, delivered nicotine bitartrate (60 mg kg(-1) d(-1)) or saline (control) for up to 28 days. In neonates, ventilation was recorded by head-out plethysmography, c-Fos (neuronal activity marker), or serotonin autoreceptors (5HT1AR) were immunodetected using light microscopy, and patch-clamp recordings were made from raphe neurons in brainstem slices under normocarbia and hypercarbia. Prenatal-perinatal nicotine exposure decreased the hypercarbia-induced ventilatory responses at P1-P5, reduced both the number of c-Fos-positive ROb neurons during eucapnic normoxia at P1-P3 and their hypercapnia-induced recruitment at P3, increased 5HT1AR immunolabeling of ROb neurons at P3-P5, and reduced the spontaneous firing frequency of ROb neurons at P3 without affecting their CO2 sensitivity or their passive and active electrical properties. These findings reveal that prenatal-perinatal nicotine reduces the activity of neonatal ROb neurons, likely as a consequence of increased expression of 5HT1ARs. This hypoactivity may change the functional state of the respiratory neural network leading to breathing vulnerability and chemosensory failure as seen in SIDS.
authors.affiliation: 1 Departamento de Fisiología, Pontificia Universidad Católica de Chile, Santiago, Chile.|2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, Chile.|Departments of 3 Neurology and.|4 Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
authors.forename: Verónica J
authors.initials: VJ
authors.lastname: Cerpa
authors.affiliation: 5 Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: María de la Luz O
authors.initials: Mde L
authors.lastname: Aylwin
authors.affiliation: 2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, Chile.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Beltrán-Castillo
authors.affiliation: 2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, Chile.
authors.forename: Eduardo U
authors.initials: EU
authors.lastname: Bravo
authors.affiliation: 2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, Chile.
authors.forename: Isabel R
authors.initials: IR
authors.lastname: Llona
authors.affiliation: Departments of 3 Neurology and.|6 Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa.|7 Veteran's Affairs Medical Center, Iowa City, Iowa; and.
authors.forename: George B
authors.initials: GB
authors.lastname: Richerson
authors.affiliation: 2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, Chile.
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Eugenín
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007223:Infant; D008431:Maternal-Fetal Exchange; D051379:Mice; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000473:pathology*; D012907:Smoking / Q000009:adverse effects; D013398:Sudden Infant Death / Q000209:etiology* / Q000473:pathology
chemical_list: D009538:Nicotine
keywords: central chemoreception; perinatal nicotine exposure; serotonin; serotonin autoreceptors; sudden infant death syndrome