Neurodevelopmental Effects of Serotonin on the Brainstem Respiratory Network.

Serotonin has multiple roles during development of the nervous system. Human pathologies, mouse genetic models, and pharmacological experiments have demonstrated a role of serotonin in the development of neural networks. Here we summarize evidence showing that serotonin is important for the brainstem respiratory network.

Early Postnatal Development of Somastostatinergic Systems in Brainstem Respiratory Network.

Somatostatin is a peptide able to stop breathing, acting in the neural network that generates and control the respiratory rhythm. In this chapter, we present data on the early postnatal development of somatostatinergic systems in the mouse brainstem and summarize evidence for their influence on the generation and control of the respiratory rhythm.

Perinatal Fluoxetine Exposure Impairs the CO2 Chemoreflex. Implications for Sudden Infant Death Syndrome.

High serotonin levels during pregnancy affect central nervous system development. Whether a commonly used antidepressant such as fluoxetine (a selective serotonin reuptake inhibitor) taken during pregnancy may adversely affect respiratory control in offspring has not been determined. The objective was to determine the effect of prenatal-perinatal fluoxetine exposure on the respiratory neural network in offspring, particularly on central chemoreception.

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

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.

Developmental origin of preBötzinger complex respiratory neurons.

A subset of preBötzinger Complex (preBötC) neurokinin 1 receptor (NK1R) and somatostatin peptide (SST)-expressing neurons are necessary for breathing in adult rats, in vivo. Their developmental origins and relationship to other preBötC glutamatergic neurons are unknown. Here we show, in mice, that the "core" of preBötC SST(+)/NK1R(+)/SST 2a receptor(+) (SST2aR) neurons, are derived from Dbx1-expressing progenitors.

Prenatal to early postnatal nicotine exposure impairs central chemoreception and modifies breathing pattern in mouse neonates: a probable link to sudden infant death syndrome.

Nicotine is a neuroteratogen and is the likely link between maternal cigarette smoking during pregnancy and sudden infant death syndrome (SIDS). Osmotic minipumps were implanted in 5-7 d CF1 pregnant mice to deliver nicotine bitartrate (60 mg Kg(-1) day(-1)) or saline (control) solutions for up to 28 d. Prenatal to early postnatal nicotine exposure did not modify the number of newborns per litter or their postnatal growth; however, nicotine-exposed neonates hypoventilated and had reduced responses to hypercarbia (inhalation of air enriched with 10% CO(2) for 20 min) and hypoxia (inhalation of 100% N(2) for 20 s) at postnatal days 0-3 (P0-P3).

Central actions of somatostatin in the generation and control of breathing.

The neuropeptide somatostatin is involved in many functions in the central nervous system as well as in the periphery. When it is centrally injected, an irreversible apnea is often developed. In the present review, we discuss the effects of somatostatin as the result of its actions at three levels of the respiratory neural network: a) by modulating the output of cranial or spinal motoneurons; b) by altering the genesis of the respiratory rhythm in the brainstem: and c) by regulating the chemosensory drive input into the respiratory pattern generator.

Somatostatin inhibition of fictive respiration is modulated by pH.

We studied the respiratory effects of the tetradecapeptide somatostatin (SST) upon fictive respiration using the in vitro brain stem spinal cord preparation from new-born mouse. We found that SST inhibits respiration, an effect that was potentiated when the chemical drive to respiration was increased. SST inhibited fictive respiration decreasing both the frequency and amplitude in a dose-dependent way.

Respiratory responses to pH in the absence of pontine and dorsal medullary areas in the newborn mouse in vitro.

The contribution of pons and dorsal medulla in establishing the pattern of fictive respiration and in mediating the respiratory response to acidification was studied using the isolated brainstem-spinal cord preparation from neonatal mouse. About 40% of ponto-medullary preparations (retaining pons) showed spontaneous, but irregular respiratory-like rhythm. In the other 60%, the elimination of the pons often was followed by the initiation of a respiratory-like rhythm.