Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Respir Cell Mol Biol. 2015 Oct;53(4):489-99. doi: 10.1165/rcmb.2014-0329OC.

The Alteration of Neonatal Raphe Neurons by Prenatal-Perinatal Nicotine. Meaning for Sudden Infant Death Syndrome.

Author information

1
1 Departamento de Fisiología, Pontificia Universidad Católica de Chile, Santiago, Chile.
2
2 Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, Chile.
3
Departments of 3 Neurology and.
4
4 Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
5
5 Facultad de Medicina, Universidad de Chile, Santiago, Chile.
6
6 Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa.
7
7 Veteran's Affairs Medical Center, Iowa City, Iowa; and.

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.

KEYWORDS:

central chemoreception; perinatal nicotine exposure; serotonin; serotonin autoreceptors; sudden infant death syndrome

PMID:
25695895
PMCID:
PMC4742896
DOI:
10.1165/rcmb.2014-0329OC
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon Icon for PubMed Central
    Loading ...
    Support Center