A slumber not so sweet: loss of brain cells that regulate breathing may cause death during sleep

Science News, August 13, 2005 by C. Brownlee

Researchers may have finally discovered how people die peacefully in their sleep. A new study in rats suggests that in elderly people, the brain gradually loses the cells that tell the body to breathe.

When old people die during slumber, physicians have typically blamed cardiac arrest. However, Jack Feldman of the University of California, Los Angeles and his colleagues hypothesize in an upcoming Nature Neuroscience that the heart shutdown is actually the result of a condition known as central sleep apnea.

Unlike obstructive sleep apnea, in which a person stops breathing when his or her airway becomes blocked, central sleep apnea occurs when brain areas that control breathing fail. Central sleep apnea is most commonly diagnosed in people who are over age 65 or who have neurodegenerative diseases. People in these groups also frequently die in their sleep.

In a previous study, Feldman and his colleagues identified a group of brain cells, called the preBotzinger complex, that seems to regulate breathing. Feldman's team injected a chemical into rats that specifically kills these cells. Within several days the animals stopped breathing and died.

To see whether gradual death of the same group of neurons might be responsible for central sleep apnea, Feldman and his team injected some rats with the same toxin used in the previous experiment and then monitored the animals during every subsequent sleep period.

At first, the scientists saw no variation from normal breathing during sleep in the rats. But after 4 days, when about half of the preBotzinger-complex neurons had been killed, the researchers observed that the animals slept fitfully.

"We were surprised to see that breathing completely stopped when the rats entered REM sleep [the deepest sleep phase], forcing the rats to wake up in order to start breathing again," says study coauthor Leanne McKay, also of the University of California, Los Angeles.

Although most of the rats died while awake, after the degeneration halted even wakeful breathing, Feldman says that he suspects that some elderly people die in their sleep from a similar chain of events. As people and other animals get older, neurons may gradually die off in the complex. Feldman hypothesizes that as night breathing problems get worse, weakened elderly people, unlike the otherwise healthy rats, can't rouse themselves when they stop breathing.

"We suspect that many humans die during sleep before ... breathing disturbances happen during wakefulness," he adds.

Atul Malhotra, a sleep researcher at Harvard University, calls Feldman's conclusion "plausible and potentially important." However, he cautions that more studies will be necessary before researchers can prove that dying preBotzinger-complex neurons cause old people to die in their sleep.

Whether or not his team's conjecture proves true, Feldman asserts that dying during sleep might still be the best way to go. He doesn't necessarily recommend developing means to combat the loss of preBotzinger-complex cells.

"We don't mean to say that stopping breathing during sleep is an uncomfortable or painful terminal event. I've had friends complain that the end result of our study is that the refuge of dying peacefully in sleep may go away," says Feluman.