Researchers look to the brain to explain gender differences in sleep apnea

The neural pathways between two areas of the brain that control the tongue -- and their interactions with each other -- may hold the key as to why men suffer sleep apnea much more than women.

A University of Wisconsin research team has theorized that either the caudal raphe or the hypoglossal nucleus -- or both together -- play roles in sleep apnea. The researchers have turned their attention to these two areas of the brain because of the roles they play in controlling the tongue. Diminished tongue control is a major cause of obstructive sleep apnea, a serious condition which strikes men much more frequently than pre-menopausal women, said lead researcher Jessica R. Barker.

*Paper presentation: "Sexual dimorphism in serotonergic input to the hypoglossal nucleus," by Jessica R. Barker and Mary Behan of the University of Wisconsin-Madison School of Veterinary Medicine, will be presented 12:45 p.m.-3 p.m. Monday April 3, Control of Breathing: Central Connectivity and Neurotransmission, 479.8 /board # C566 in the Convention Center Exhibit Hall. Poster is on view 7:30 a.m. to 6 p.m.

Sleep apnea affects millions of Americans, produces loud snoring and may interfere with the sleep of other family members. It leaves sufferers drowsy during the day and places them at greater risk of getting into an automobile accident and of developing serious illnesses such as hypertension and heart disease.

Estrogen, serotonin play roles

Previous research from Behan's lab has found evidence that estrogen plays a role in respiratory control and may provide protection against hypoxia. Other research shows that post-menopausal women on hormone replacement therapy suffer less from sleep apnea than post-menopausal women not on hormones, further strengthening the theory that estrogen plays a protective role.

The unique theory could explain why men and post-menopausal women not on hormone therapy are much more likely to suffer from the condition than pre-menopausal women, Barker said.

Estrogen is associated with serotonin, a neurotransmitter that helps control the tongue. In obstructive sleep apnea, the tongue relaxes too much during sleep and blocks the upper airway, causing the individual to temporarily stop breathing. The cycle repeats throughout the sleep period, creates periods of insufficient oxygen and disrupts sleep.

The purpose of the Barker study is to determine if the difference in estrogen levels between men and women plays a role in serotonin expression in the caudal raphe and hypoglossal nucleus -- leading to a difference in tongue control.

The researchers hypothesized that females would have greater numbers of serotonin-activated neurons running between the hypoglossal nucleus and the tongue. They first looked at the caudal raphe because that is where serotonin which plays a role in preventing the tongue from relaxing and blocking the airway -- is manufactured.

Targets: serotonin, hypoglossal nucleus, caudal raphe,

The researchers used six young male rats and six females. They injected the rats' tongues under anesthesia with a tracer, Bartha pseudorabies virus (PRV). They examined the pathway of the virus into the brain and were able to "see" the path of the PRV and the serotonin-activated neurons projecting from the caudal raphe to the tongue.

They looked at the number and distribution of neurons activated by serotonin in the caudal raphe, expecting there would be differences between males and females. Instead, they found male and female rats have the same number of serotonin producing neurons in this area of the brain.

The study suggests the caudal raphe does not play a role -- at least by itself -- in obstructive sleep apnea. Researchers will next look at the neurons producing serotonin that run from the hypoglossal nucleus to the tongue, explained Barker.

Also in the future: a look at the interactions among the caudal raphe, the hypoglossal nucleus and the tongue. The key may be in how these structures interact, she said.

If this line of research eventually pans out, it may be possible to adjust hormone levels to relieve the sleep apnea and avoid the resultant health problems, Barker said.

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Funding: National Institutes of Health and National Center for Research Resources.

Editor's Note: For further information or to schedule an interview with a member of the research team, please contact Christine Guilfoy at the APS newsroom @ 415.905.1024 (March 31-April 5); 978.290.2400 (cell), 301.634.7253 (office), or cguilfoy@the-aps.org; or Mayer Resnick or 301.332.4402 (cell) or 301.634.7209 (office).

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