Researchers from the Geisel School of Medicine at Dartmouth, NH, recently investigated the role of serotonin on breathing responses in sleeping infants. The findings, published in Experimental Physiology, offer a new avenue of research into sudden infant death syndrome.

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New research demonstrates that serotonin, apnea, and SIDS appear to be interlinked.

Sudden infant death syndrome (SIDS) refers to the unexplained death of a baby who seems otherwise healthy.

SIDS is also known as crib death as it most commonly occurs while the child is sleeping.

In the United States, an estimated 1,500 children under 12 months die from SIDS yearly.

Some factors that raise the risk of SIDS have been uncovered. These include children with brain abnormalities, low birth weight, or respiratory infections; however, the exact causes are still poorly understood.

Guidelines are in place to help minimize the risk of SIDS; for instance, babies sleeping on their side or stomach can have more difficulty breathing, soft, fluffy surfaces are more likely to block airways, and babies sleeping in bed with parents is not recommended.

Since 1990, SIDS has declined significantly, from 130.3 deaths per 100,000 to 38.7 per 100,000 in 2014. This demonstrates that an overall growth in awareness, alongside the suggested physical interventions, has had a substantial impact. Despite this, researchers are still striving to reduce numbers further.

Serotonin and the brainstem

SIDS and asphyxia (a lack of oxygen) are the leading causes of death in infants under 12 months of age, and there are still no effective treatments. Prof. James Leiter and his team at Geisel School of Medicine set out to investigate the neuroscience behind SIDS and close the knowledge gap further.

The team's research follows on from previous findings demonstrating that the brainstems of infants who died of SIDS were deficient in both serotonin and serotonin receptors. The team decided to broaden these findings and investigate whether serotonin could shorten apnea (temporary breaks in breathing) and whether blocking serotonin would lengthen apnea.

"Serotonin is important in arousing infants and restoring regular breathing to end apneic events when regular breathing is interrupted."

Prof. James Leiter, MD

The research was carried out in an animal model, using rat pups. The team inserted small quantities of water into the upper respiratory tracts of the rodents, which induced reflex apnea, also referred to as laryngeal chemoreflex. This reflex produces apnea and slows heart rate.

Laryngeal chemoreflex is a natural response found in adults, but it seems to occur more readily in infants. Some researchers believe that the laryngeal chemoreflex might be the starting point of SIDS.

Shortening the laryngeal chemoreflex

To understand the role of serotonin, the investigators injected small amounts of serotonin-altering drugs into the brainstems of the rat pups and observed any changes to the duration of the laryngeal chemoreflex.

Prof. Leiter and his team discovered that when serotonin was injected into the brainstem, the apnea reduced in duration from around 10 seconds to 2 seconds. This effect was only measured when a specific type of serotonin receptor was activated - the 5HT3 receptor.

These findings dovetail neatly with earlier results. Serotonin is found to be reduced in infants who have died of SIDS, and this new evidence shows that serotonin does indeed reduce apnea events in rat pups.

"This is the first time, I think, that animal studies have taken the lead in SIDS research, so I found the work quite rewarding. But there is always more to do."

Prof. James Leiter, MD

The team plans to continue their line of research. Specifically, they hope to understand whether babies who die of SIDS are deficient in 5HT3 receptors. Other brain regions that might be involved in the laryngeal chemoreflex will also come under scrutiny.

Additionally, the team hopes to be able to induce SIDS in rat pups by altering the conditions in which their mothers live prior to birth. According to Prof. Leiter, the end goal is "to figure out how best to adapt drugs for use in human babies that interact with reflex apnea and arousal responses so that they may be studied and used effectively to prevent SIDS and asphyxial deaths in babies."

The work continues, but SIDS researchers hope that these findings will help medical scientists enter a new and more focused phase of investigation.

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