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 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.

Pre‐ and early postnatal nicotine exposure exacerbates autoresuscitation failure in serotonin‐deficient rat neonates

“…Cerpa et al . () recently further showed that the increased 5‐HT 1A R expression in raphe 5‐HT neurons is accompanied by reduced spontaneous firing frequency and reduced hypercapnia activated c‐ Fos ‐positive 5‐HT neuron numbers in the raphe obscurus of P3–5 mice. Taken together, results of these studies suggest that perinatal nicotine exposure can lead to a dysfunctional 5‐HT system in the neonate offspring, and the phenotypes observed in our current study may reflect the results of the combination of nicotine exposure and 5‐HT deficiency.…”

Síndrome da morte súbita infantil em Pelotas de 2006 a 2013: uma análise descritiva

“…Shatet al 17 estimou que 20,7% dos casos de SMSI poderiam ser prevenidos se mães não fumassem durante gravidez. Estudos apontam que o tabagismo é um potente fator de risco para SMSI 10,18 , mas também um dos que mais facilmente pode ser evitado, fato que reitera importância de políticas públicas anti-tabagismo especialmente durante gestação. Em nosso estudo, encontramos que 29 (78%) das mães eram tabagistas.…”

Central and peripheral chemoreceptors in sudden infant death syndrome

“…Lei et al (2015) report that, in medullary slices sampled from prenatally exposed rats, responses to acidification (increased burst frequency and reduced integrated amplitude) are lower than in controls, indicating a blunting effect on central chemoreception. In mouse, prenatal to early postnatal nicotine exposure also causes specific changes in the raphe obscurus nucleus (decreased number of serotoninergic neurons and increased expression of 5-HT 1A autoreceptors) (Cerpa et al 2015).…”

“…In mouse, prenatal to early postnatal nicotine exposure also causes specific changes in the raphe obscurus nucleus (decreased number of serotoninergic neurons and increased expression of 5‐HT 1A autoreceptors) (Cerpa et al . ).…”