Prenatal to Early Postnatal Nicotine Exposure Impairs Central Chemoreception and Modifies Breathing Pattern in Mouse Neonates: A Probable Link to Sudden Infant Death Syndrome

Eugenı́n, Jaime; Otárola, Marcelo; Bravo, Eduardo; Coddou, Claudio; Cerpa, Verónica; Reyes‐Parada, Miguel; Llona, Isabel; Bernhardi, Rommy von

doi:10.1523/jneurosci.4441-08.2008

Cited by 75 publications

(105 citation statements)

References 56 publications

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“…68,69 Functional correlates of nicotine exposure include hypoventilation and apnea, as well as blunted chemoreflexes in response to hypoxia. [70][71][72] Studies in human fetal subjects who have been exposed to nicotine have provided a better understanding of the molecular mechanisms underlying the developmental behaviors seen with prenatal nicotine exposure. For example, researchers have found that prenatal cigarette e7 by guest on May 12, 2018 http://pediatrics.aappublications.org/ Downloaded from exposure is associated with a decrease in the expression of the genes related to the endogenous opioid system in areas of the brain, the nucleus accumbens, that have been implicated in behavior motivation and mood regulation.…”

Section: Health Consequences Of Exposure To Nicotinementioning

confidence: 99%

Nicotine and Tobacco as Substances of Abuse in Children and Adolescents

Siqueira¹,

Ryan²,

Gonzalez³

et al. 2017

Pediatrics

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Nicotine is the primary pharmacologic component of tobacco, and users of tobacco products seek out its effects. The highly addictive nature of nicotine is responsible for its widespread use and difficulty with quitting. This technical report focuses on nicotine and discusses the stages of use in progression to dependence on nicotine-containing products; the physiologic characteristics, neurobiology, metabolism, pharmacogenetics, and health effects of nicotine; and acute nicotine toxicity. Finally, some newer approaches to cessation are noted.

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Section: Health Consequences Of Exposure To Nicotinementioning

confidence: 99%

Nicotine and Tobacco as Substances of Abuse in Children and Adolescents

Siqueira¹,

Ryan²,

Gonzalez³

et al. 2017

Pediatrics

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“…In fact, prenatalperinatal nicotine exposure causes hypoventilation (19,20), increased apnea periods during normoxia in mice and rats (21), reduction of hypercarbia-and hypoxiainduced ventilatory chemoreflexes in mice (19), rats (20,22), and sleeping lambs (23), reduction of autoresuscitation from primary apnea in rats (24), and delays in the hypoxiainduced awakening response in lambs (23). In the serotonergic system, prenatal nicotine increases serotonin 5-HT 1A R binding in the ROb of baboon fetuses (25) as perinatal tobacco exposure does in the cerebral cortex of rhesus monkeys (26).…”

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confidence: 99%

“…Blunting of ventilatory chemoreflexes in nicotine-exposed mice is due, in part, to a failure in central chemoreception (19,30). We hypothesized that, in mouse neonates, raphe neurons, which express functional nicotinic acetylcholine receptors (31,32), could be targeted by prenatal-perinatal nicotine exposure, affecting their activities, their electrical properties, and their chemosensitivities.…”

mentioning

confidence: 99%

“…We hypothesized that, in mouse neonates, raphe neurons, which express functional nicotinic acetylcholine receptors (31,32), could be targeted by prenatal-perinatal nicotine exposure, affecting their activities, their electrical properties, and their chemosensitivities. We studied CF1 neonates at Postnatal Days 1 (P1) to P8, because it is known that, within this period, prenatal cigarette smoke disrupts eupneic breathing and the ventilatory response to hypoxia in rats (33), whereas prenatal-perinatal nicotine exposure impairs ventilatory responses to hypercapnia and depresses central respiratory chemoreception in mice (19,30). Therefore, we expect that the diminished hypercarbiainduced ventilatory responses that occur in nicotine-exposed mice at P1-P3 will be accompanied at the same time by changes in the electrical properties or CO 2 responsiveness of raphe neurons, including both the serotonergic and nonserotonergic populations.…”

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confidence: 99%

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

Cerpa

Aylwin

Beltrán-Castillo

et al. 2015

Am J Respir Cell Mol Biol

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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 21 d 21 ) 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 (5HT 1A R) 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 hypercarbiainduced 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 5HT 1A R immunolabeling of ROb neurons at P3-P5, and reduced the spontaneous firing frequency of ROb neurons at P3 without affecting their CO 2 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 5HT 1A Rs. This hypoactivity may change the functional state of the respiratory neural network leading to breathing vulnerability and chemosensory failure as seen in SIDS.

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“…Although some respiratory cells are present at depths of at least 200 mm below the surface, others are within one or two cell diameters of the surface and are stained by bath application of dye. Recent histological studies by one of us (Eugenin et al 2008) has confirmed that there are few glia present in the mouse brainstem at post-natal day 1, which strongly suggests that the cells that are stained and giving signals are certainly neurons and not glia.…”

Section: Discussionmentioning

confidence: 95%

Optical analysis of circuitry for respiratory rhythm in isolated brainstem of foetal mice

Muller

Tsechpenakis

Homma

et al. 2009

Phil. Trans. R. Soc. B

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Respiratory rhythms arise from neurons situated in the ventral medulla. We are investigating their spatial and functional relationships optically by measuring changes in intracellular calcium using the fluorescent, calcium-sensitive dye Oregon Green 488 BAPTA-1 AM while simultaneously recording the regular firing of motoneurons in the phrenic nerve in isolated brainstem/spinal cord preparations of E17 to E19 mice. Responses of identified cells are associated breath by breath with inspiratory and expiratory phases of respiration and depend on CO 2 and pH levels. Optical methods including two-photon microscopy are being developed together with computational analyses. Analysis of the spatial pattern of neuronal activity associated with respiratory rhythm, including cross-correlation analysis, reveals a network distributed in the ventral medulla with intermingling of neurons that are active during separate phases of the rhythm. Our experiments, aimed at testing whether initiation of the respiratory rhythm depends on pacemaker neurons, on networks or a combination of both, suggest an important role for networks.

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Prenatal to Early Postnatal Nicotine Exposure Impairs Central Chemoreception and Modifies Breathing Pattern in Mouse Neonates: A Probable Link to Sudden Infant Death Syndrome

Abstract: Nicotine is a neuroteratogen and is the likely link between maternal cigarette smoking during pregnancy and sudden infant death syndrome (SIDS).

Cited by 75 publications

References 56 publications

Nicotine and Tobacco as Substances of Abuse in Children and Adolescents

Nicotine and Tobacco as Substances of Abuse in Children and Adolescents

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

Optical analysis of circuitry for respiratory rhythm in isolated brainstem of foetal mice

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