Science + Technology

UCLA Study Links Nighttime Dying to Sleep Apnea From Brain Cell Loss


Aim to grow old and die peacefully in your sleep? Be carefulwhat you wish for. A new UCLA study suggests that some people die in theirsleep because they stop breathing due to a cumulative loss of cells in thebrain's breathing command post. The online edition of Nature Neurosciencereports the findings on Aug. 7.

"We wanted to reveal the mechanism behind central sleepapnea, which most commonly affects people after age 65," said Jack Feldman,principal investigator and distinguished professor of neurobiology at the DavidGeffen School of Medicine at UCLA. "Unlike obstructive sleep apnea — in which aperson stops breathing when their airway collapses — central sleep apnea istriggered by something going awry in the brain's breathing center."

Feldman's team had earlier pinpointed a brainstem regionthey dubbed the preBtzinger complex (preBtC) as thecommand post for generating breathing in mammals, and identified a small groupof preBtC neuronsresponsible for issuing the commands.

This time, the researchers studied the role of the preBtC neurons ingenerating breathing during sleep, and what would happen if these brain cellswere destroyed.

The scientists injected adult rats with a cell-specificcompound to target and kill more than half of the specialized preBtC neurons. Then theteam monitored the rats' breathing patterns. After four or five days, theresults proved visibly dramatic.

"We were surprised to see that breathing completely stopped when the rat entered REM sleep, forcingthe rat to wake up in order to start breathing again," said LeanneMcKay, postdoctoral fellow in neurobiology. "Over time, the breathing lapsesincreased in severity, spreading into non-REM sleep and eventually occurringwhen the rats were awake, as well."

Because mammals' brains are organized in a similar fashion,the scientists believe that the rat findings are relevant to the human brain.Rats possess 600 specialized preBtC cells, andFeldman theorizes that humans have a few thousand, which are slowly lost over alifetime.

"Our research suggests that the preBtzingercomplex contains a fixed number of neurons that we lose as we age," Feldmansaid. "Essentially, we sped up these cells' aging process in the rats overseveral days instead of a lifetime."

Long before the rats had difficulty breathing when awake,they developed a breathing problem during sleep. The UCLA team suspects thesame thing happens as people grow older.

"We speculate that our brains can compensate for up to a 60percent loss of preBtC cells, but the cumulativedeficit of these brain cells eventually disrupts our breathing during sleep.There's no biological reason for the body to maintain these cells beyond theaverage lifespan, and so they do not replenish as we age," Feldman said. "As welose them, we grow more prone to central sleep apnea."

When elderly but otherwise healthy people die during sleep,physicians commonly record the cause of death as heart failure. The UCLA teambelieves that the loss of preBtC neurons sparkscentral sleep apnea, causing elderly people whose lungs and heart are alreadyweaker due to age, to stop breathing and succumb to death in their sleep. Theirtrue cause of death goes undetected.

The scientists suspect central sleep apnea also strikespeople suffering the late stages of neurodegenerative disorders, such asParkinson's disease, Lou Gehrig's disease andmultiple system atrophy, all serious conditions that lead to movement problems.

"People with these diseases breathe normally when they areawake, but many of them have breathing difficulties during sleep," said Wiktor Janczewski, assistant researcherin neurobiology. "When central sleep apnea strikes, they are alreadyvery ill and their sleep‑disordered breathing may go unnoticed.

"As the patients grow sicker, their nighttime threshold forwakefulness rises," he said."Eventually, their bodies reach a point when they are unable to rousethemselves from sleep when they stop breathing, and they die from lack ofoxygen."

The UCLA team will repeat their research with elderly ratsin order to learn why central sleep apnea first strikes during REM sleep. Thegroup also plans to analyze the brains of people who die from neurodegenerativediseases to determine whether these patients show damage in their preBtzinger complexes.

The National Heart, Lung and Blood Institute funded theresearch.



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