Nighttime Dying Linked To Sleep Apnea From Brain Cell Loss

"We wanted toreveal the mechanism behind central sleep apnea, which most commonlyaffects people after age 65," explained Jack Feldman, principalinvestigator and Distinguished Professor of Neurobiology at the DavidGeffen School of Medicine at UCLA. "Unlike obstructive sleep apnea – inwhich a person stops breathing when their airway collapses -- centralsleep apnea is triggered by something going awry in the brain'sbreathing center."

Feldman's team had earlier pinpointed abrainstem region they dubbed the preBötzinger complex (preBötC) as thecommand post for generating breathing in mammals, and identified asmall group of preBötC neurons responsible for issuing the commands.This time, the researchers studied the role of the preBötC neurons ingenerating breathing during sleep, and what would happen if these braincells were destroyed.

The scientists injected adult rats with acell-specific compound to target and kill more than half of thespecialized preBötC neurons. Then the team monitored the rats'breathing patterns. After four or five days, the results proved visiblydramatic.

"We were surprised to see that breathing completelystopped when the rat entered REM sleep, forcing the rat to wake up inorder to start breathing again," said Leanne McKay, postdoctoral fellowin neurobiology. "Over time, the breathing lapses increased inseverity, spreading into non-REM sleep and eventually occurring whenthe rats were awake, as well."

Because mammals' brains areorganized in a similar fashion, the scientists believe that the ratfindings are relevant to the human brain. Rats possess 600 specializedpreBötC cells, and Feldman theorizes that humans have a few thousand,which are slowly lost over a lifetime.

"Our research suggeststhat the preBötzinger complex contains a fixed number of neurons thatwe lose as we age," said Feldman. "Essentially, we sped up these cells'aging process in the rats over several days instead of a lifetime."

Longbefore the rats had difficulty breathing when awake, they developed abreathing problem during sleep. The UCLA team suspects the same thinghappens as people grow older.

"We speculate that our brains cancompensate for up to a 60 percent loss of preBötC cells, but thecumulative deficit of these brain cells eventually disrupts ourbreathing during sleep. There's no biological reason for the body tomaintain these cells beyond the average lifespan, and so they do notreplenish as we age," said Feldman. "As we lose them, we grow moreprone to central sleep apnea."

When elderly but otherwise healthypeople die during sleep, physicians commonly record the cause of deathas heart failure. The UCLA team believes that the loss of preBötCneurons sparks central sleep apnea, causing elderly people whose lungsand heart are already weaker due to age, to stop breathing and succumbto death in their sleep. Their true cause of death remains unknown.

Thescientists suspect central sleep apnea also strikes people sufferingthe late stages of neurodegenerative disorders, such as Parkinson'sdisease, Lou Gehrig's disease and multiple system atrophy, all seriousconditions that lead to movement problems.

"People with thesediseases breathe normally when they are awake, but many of them havebreathing difficulties during sleep," said Wiktor Janczewski, assistantresearcher in neurobiology. "When central sleep apnea strikes, they arealready very ill and their sleep-disordered breathing may go unnoticed.

"Asthe patients grow sicker, their nighttime threshold for wakefulnessrises," he added. "Eventually, their bodies reach a point when they areunable to rouse themselves from sleep when they stop breathing, andthey die from lack of oxygen."

The UCLA team will repeat theirresearch with elderly rats in order to learn why central sleep apneafirst strikes during REM sleep. The group also plans to analyze thebrains of people who die from neurodegenerative diseases to determinewhether these patients show damage in their preBötzinger complexes.

The National Heart, Lung and Blood Institute funded the research.