Nighttime dying linked to sleep apnea from brain cell loss
August 8, 2005
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 on
Aug. 7.
"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."
When elderly but otherwise healthy people die during sleep, physicians commonly
record the cause of death as heart
failure. The UCLA team believes that the loss of preBötC neurons sparks
central sleep apnea, causing elderly people whose lungs and heart are already
weaker due to age, to stop breathing and succumb to death in their sleep. Their
true cause of death remains unknown.
The scientists suspect central sleep apnea also strikes people suffering the
late stages of neurodegenerative disorders, such as Parkinson's disease, Lou
Gehrig's disease and multiple system atrophy, all serious conditions that lead
to movement problems.
"People with these diseases breathe normally when they are awake, but many
of them have breathing difficulties during sleep," said Wiktor Janczewski,
assistant researcher in neurobiology. "When central sleep apnea strikes,
they are already very ill and their sleep-disordered breathing may go unnoticed.
"As the patients grow sicker, their nighttime threshold for wakefulness
rises," he added. "Eventually, their bodies reach a point when they
are unable to rouse themselves from sleep when they stop breathing, and they die
from lack of oxygen."
The UCLA team will repeat their research with elderly rats in order to learn why
central sleep apnea first strikes during REM sleep. The group also plans to
analyze the brains of people who die from neurodegenerative diseases to
determine whether these patients show damage in their preBötzinger complexes.
The National Heart, Lung and Blood Institute funded the research.
Elaine Schmidt
eschmidt@mednet.ucla.edu
310-794-2272
University of California - Los Angeles
http://www.newsroom.ucla.edu