Journal article
The Alteration of Neonatal Raphe Neurons by Prenatal-Perinatal Nicotine. Meaning for Sudden Infant Death Syndrome
American journal of respiratory cell and molecular biology, Vol.53(4), pp.489-499
10/2015
DOI: 10.1165/rcmb.2014-0329OC
PMCID: PMC4742896
PMID: 25695895
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.
Details
- Title: Subtitle
- The Alteration of Neonatal Raphe Neurons by Prenatal-Perinatal Nicotine. Meaning for Sudden Infant Death Syndrome
- Creators
- Verónica J Cerpa - 4 Facultad de Medicina, Universidad del Desarrollo, Santiago, ChileMaría de la Luz O Aylwin - 5 Facultad de Medicina, Universidad de Chile, Santiago, ChileSebastián Beltrán-Castillo - 2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, ChileEduardo U Bravo - 2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, ChileIsabel R Llona - 2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, ChileGeorge B Richerson - 7 Veteran's Affairs Medical Center, Iowa City, Iowa; andJaime L Eugenín - 2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, Chile
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.53(4), pp.489-499
- DOI
- 10.1165/rcmb.2014-0329OC
- PMID
- 25695895
- PMCID
- PMC4742896
- NLM abbreviation
- Am J Respir Cell Mol Biol
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Publisher
- United States
- Grant note
- R01 HD052772 / NICHD NIH HHS P01 HD036379 / NICHD NIH HHS P01HD36379 / NICHD NIH HHS U01 NS090414 / NINDS NIH HHS R01HD052772 / NICHD NIH HHS
- Language
- English
- Date published
- 10/2015
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020789002771
Metrics
34 Record Views