INFANT DEATH: NICOTINE IN QUESTION
Work conducted in a collaboration between the laboratories of Jean-Pierre Changeux* at the Institut Pasteur, Hugo Lagercrantz at the Karolinska Institute of Stockholm (Sweden), and Philippe Evrard at the Hôpital Robert Debré in Paris demonstrates the involvement of a nicotinic receptor in regulating respiratory reflexes during sleep - reflexes which, if they are altered, can lead to respiratory arrest and to death. This study, published in the Proceedings of the National Academy of Sciences USA (PNAS), can explain why - according to the epidemiological research completed up to this point - exposure to nicotine during pregnancy is the most important risk factor associated with Sudden Infant Death Syndrome (SIDS). The researchers hope that their studies will aid in developing methods to prevent this syndrome in at-risk newborns. Sudden Infant Death remains the biggest cause of death in France in a child's first year of life.
* Professor at the Collège de France and at the Institut Pasteur and head of Receptors and Cognition Unit associated with the CNRS D1284 .
Nicotine binds itself in the brain to specific molecules called receptors, which are naturally present to interact with a neurotransmitter which intervenes in numerous bodily functions - acetylcholine. There exists within the rich family of acetylcholine receptors some which bind nicotine, also called cholinergic nicotinic receptors. While studying a particular type of nicotinic receptor (containing the ß2 subunit: ß2 nAChR)), the researchers put their finger on a mechanism which can explain the harmful effects of nicotine within SIDS.
Previous studies had already shown that this receptor intervened in learning behaviors in animals while awake. The findings published today demonstrate that it also plays a role in regulating breathing during sleep, notably in the vital reflexes engaged by the organism faced with a lack of oxygen.
It is known that the lack of oxygen during sleep, which can occur spontaneously in the form of brief respiratory pauses (apnea), normally triggers a powerful cardio-respiratory stimulation and arousal. If this protective reflex response is altered, apnea and hypoxia are exacerbated and can lead to respiratory arrest, a probable cause of SIDS.
Using genetically modified mice (deprived of ß2 subunit) and wild type mice, the researchers compared the effects of normal oxygenation with weak oxygenation (hypoxia), in conditions which reproduce apnea, which commonly occurs in our sleep. These experiments were conducted, without and then with nicotine injection, using a device (a plethysmograph) that makes it possible to measure a mouse's breathing while observing its arousal reactions.
The researchers proved that the reflex response to the lack of oxygen is diminished in the ß2 subunit invalidated mice, suggesting the involvement of the ß2 nAChR receptor in this response. Moreover, they highlighted the harmful effects of nicotine, which attenuates these vital mechanisms.
The researchers advance the theory that nicotine, transmitted (through the blood) by a smoking mother to her fetus, would lead to a continued activation of the nicotinic receptor containing the ß2 subunit during pregnancy, which as a consequence would cause in the newborn a diminished effectiveness of the respiratory and arousal reflexes in response to sleep apnea, and thus an augmented risk of sudden infant death.
Clarifying the role played
by the nicotinic receptor ß2 nAChR could help in the development of therapeutic
approaches allowing the prevention of SIDS by treating at-risk newborns, even
though the first line of prevention remains the cessation of smoking during
- "ß2 nicotinic
acetylcholine receptor subunit modulates protective responses to stress: A receptor
basis for sleep-disordered breathing after nicotine exposure": PNAS.
Gary Cohen*, Zhi-Yan Han¤, Régis Grailhe¤, Jorge Gallego*, Claude Gaultier*, Jean-Pierre Changeux¤ and Hugo Lagercrantz§
* Developmental Neurobiology and Physiology Laboratory, INSERM E9935, Hôpital Robert Debré, Paris, France
¤ CNRS Associated Unit D1284 Receptors and Cognition, Institut Pasteur, Paris, France
§ Neonatal Unit, Karolinska Institute, Stockholm, Sweden
- Jean-Pierre Changeux,
Institut Pasteur (Paris, France)
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- Hugo Lagercrantz,
Karolinska Institute (Stockholm, Sweden)
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- Claude Gaultier,
Hôpital Robert Debré (Paris, France)
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