Mar 272006
Authors: Susanne Rust Milwaukee Journal Sentinel

MILWAUKEE – An international team of researchers has identified a specific receptor in the brain that, if faulty, may be involved in sudden infant death syndrome, or SIDS.

The team, led by Medical College of Wisconsin physiologist Andrew Tryba, adds critical information to a growing body of research that shows serotonin receptors may be involved in an infant’s ability to gasp – and therefore breathe – in low-oxygen conditions. This gasping mechanism is thought to fail in SIDS victims.

SIDS is the No. 1 killer of 1-month to 1-year-old children in the United States, said Tryba. About 3,000 infants die each year from SIDS, according to the Centers for Disease Control and Prevention.

The study was published this month in the journal Neuroscience.

“This really ties into a number of things that have already been observed,” said Donald McCrimmon, a physiologist at Northwestern University, who was not involved in the study. “It’s a strong addition to the literature out there.”

Throughout the human body, there are critical cells called pacemakers. These cells, which are found in the heart, brain and elsewhere, generate rhythmic activities without external influences. For example, pacemaker cells in the heart are needed to trigger the rhythmic heartbeat. There are pacemakers in the brainstem that trigger rhythmic breathing, as well.

For years, Tryba has been interested in these kinds of cells, and the rhythmic activities that organisms display. His earliest work was focused on the generation of locomotion in insects.

“Although that was interesting, I wanted to do something more applicable,” he said. “Something that could potentially make a difference in people.”

That’s when he got interested in SIDS and hooked up with his co-writers on the paper, Fernando Pena, of the Department of Pharmacology at Cinvestav-Coapa, in Mexico, and Jan-Marino Ramirez, at the University of Chicago.

Victims of SIDS previously have been identified as having abnormal serotonin receptors in brainstem areas controlling breathing. Since serotonin regulates the ability of pacemaker cells to respond and work properly, Tryba and his team decided to take a closer look at these cells – particularly those located in the region of the brain that controls breathing.

Earlier work by this team – published last year in the journal Neuron – had shown that some pacemaker neurons, located in the brainstem, generated a gasping mechanism in hypoxic, or low oxygen, conditions. But how that worked, and what receptors on the cell were critical for this function, was unclear.

For this study, the researchers took tissue samples from brain stems of mice and recorded the electrical activity of the pacemaker cells under different conditions.

They found that if they blocked a specific receptor – one called the 5-HT2A receptor – during low-oxygen conditions, the electrical activity, which underlies the gasping reflex, was eliminated.

The research, said Tryba, suggests that if this specific receptor is faulty in children, it will reduce their ability to respond appropriately when deprived of oxygen – conditions that could occur if their noses and mouths are somehow blocked.

But, said Tryba, a lot more work will need to be done to cement the connection and then translate it into useful screening or therapeutic treatments for children at risk.

In the meantime, he stressed that the best defense against SIDS was to place babies on their backs when set in their cribs, and to keep all extraneous items, such as pillows, blankets and stuffed animals, out of the crib.

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