The Myth Behind Sudden Infant Death Syndrome Revealed

A recent study could explain the mystery behind sudden infant death syndrome (SIDS) in human babies, which is considered to be linked with dysfunctional airway sensory neurons.

A newly discovered protein called Piezo2 at The Scripps Research Institute (TSRI) seems to be associated in how the body controls breathing, according to a recent study performed by scientists at TSRI and Harvard Medical School.

“The findings here might offer essential clues on how to treat patients with respiratory disorders” noted senior author Ardem Patapoutian, who serves as a professor at TSRI and also as a Howard Hughes Medical Institute (HHMI) investigator.

Using genetically engineered mouse models, the researchers discovered that newborn mice without the Piezo2 channel exhibit critical respiratory distress that causes death. Adult mice without the Piezo2 channel in sensory neurons show remarkable raise in tidal volume which is the amount of inhaled air in lungs, in addition to an impaired Hering-Breuer reflex (an inhibitory respiratory reflex that blocks lung over-expansion).

Piezo2 And Lung Functions

The Piezo2 ion channel was at first discovered as a new mechanosensor which means that the sensor of mechanical stimuli such as pressure or stretch, in Patapoutian’s lab in 2010. Further studies revealed that the Piezo2 channel seen in sensory neurons is needed for sensing touch sensation and muscle stretch in mice. These studies made researchers to speculate if Piezo2 has a role as a common stretch sensor in other organs such as lungs.

“Earlier studies proposed the occurrence of lung inflation sensors; though, their molecular identity or physiological significance has not been explained,” said Patapoutian.

The researchers dealt this question by making and characterizing Piezo2 “knockout” mice, in which the Piezo2 channel is removed throughout the animal or only from sensory neurons (more particularly, vagal sensory neurons that are recognized to manage breathing). They discovered that Piezo2 is important for proper breathing and lung expansion in newborn mice. Piezo2-deficient newborn mice exhibited unexpanded lungs and considerably shallow breathing.

“The lungs interact with the brain via sensory neurons. The Piezo2 channel in sensory neurons creates a message about lung volume changes, and Piezo2-containing sensory neurons convey this message to the brain,” explained TSRI Research Associate Keiko Nonomura, who is the co-first author of the study and along with TSRI Research Associate Seung-Hyun Woo. “Piezo2-deficient mice were unable to create an accurate message regarding their lung volume changes. Consequently, these mice were unable to receive appropriate output from the brain.”

Prominently, as per recently published papers, Piezo2-deficient human infants also exhibit shallow breathing and need medical attention.

“Piezo2-deficient newborn mice grow normally until birth. The problem only arises when the mice are born and try to breathe on their own,” stated Nonomura.

Understanding sudden infant death syndrome and other respiratory diseases

The researchers were amazed to notice a surprising result of removing Piezo2 in sensory neurons of adult mice. When the Piezo2 channel was removed either in all sensory neurons or only from vagal sensory neurons, adult mice could do breathing, but they inhaled remarkably more air than Piezo2-intact mice.

Under standard conditions, animals halt breathing when they are forced to breathe in more air, but Piezo2-deficient adult mice without the Hering-Breuer reflex keep on breathing when they were forced to inhale more air.

Why this variation between adults and newborns? The researchers discovered that Piezo2 has different roles in newborns and adults because establishing independent breathing in newborns is more difficult.

“At birth, the respiratory system of newborn experiences drastic structural modifications, as liquid-filled compressed fetal airways are being cleared out and filled with air,” noted Patapoutian. “Hence, newborn airways undergo larger mechanical changes when compared to adult airways which have previously established regular breathing.”

These data, for the first time, describe the significance of mechanosensory transduction in adult respiration. This research is also applicable for understanding respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and sleep apnea, which seems to be linked to disruption of the airway sensory feedback system.

The team mentioned that future studies could also utilize the same genetic manipulations to better understand the work of Piezo2 in other physiological processes such as heart rate control and bladder function.

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