Aim to grow old and die peacefully in your sleep? Be careful what you wish for. A new UCLA study suggests that some people die in their sleep because they stop breathing due to a cumulative loss of cells in the brain's breathing command-post. The online edition of Nature Neuroscience reports the findings.
"We wanted to reveal the mechanism behind central sleep apnea, which most commonly affects people after age 65," explained Jack Feldman, principal investigator and Distinguished Professor of Neurobiology at the David Geffen School of Medicine at UCLA. "Unlike obstructive sleep apnea – in which a person stops breathing when their airway collapses -- central sleep apnea is triggered by something going awry in the brain's breathing center."
Feldman's team had earlier pinpointed a brainstem region they dubbed the preBötzinger complex (preBötC) as the command post for generating breathing in mammals, and identified a small group of preBötC neurons responsible for issuing the commands. This time, the researchers studied the role of the preBötC neurons in generating breathing during sleep, and what would happen if these brain cells were destroyed.
The scientists injected adult rats with a cell-specific compound to target and kill more than half of the specialized preBötC neurons. Then the team monitored the rats' breathing patterns. After four or five days, the results proved visibly dramatic.
"We were surprised to see that breathing completely stopped when the rat entered REM sleep, forcing the rat to wake up in order to start breathing again," said Leanne McKay, postdoctoral fellow in neurobiology. "Over time, the breathing lapses increased in severity, spreading into non-REM sleep and eventually occurring when 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 preBötC cells, and Feldman theorizes that humans have a few thousand, which are slowly lost over a lifetime.
"Our research suggests that the preBötzinger complex contains a fixed number of neurons that we lose as we age," said Feldman. "Essentially, we sped up these cells' aging process in the rats over several 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 the same thing happens as people grow older.
"We speculate that our brains can compensate for up to a 60 percent loss of preBötC cells, but the cumulative deficit of these brain cells eventually disrupts our breathing during sleep. There's no biological reason for the body to maintain these cells beyond the average lifespan, and so they do not replenish as we age," said Feldman. "As we lose them, we grow more prone to central sleep apnea."