Photomicrograph of serotonin containing axons (green) in close
proximity to hypoglossal nerve cells (red).
little is known about the effects of age on regions of the brain
and spinal cord that are involved in the control of respiration.
We believe that aging results in structural and functional changes
in these respiratory control areas that may predispose people to
breathing disorders. Moreover, we hypothesize that age-associated
changes in respiratory areas of the brain and spinal cord are quite
different in men and women.
am particularly interested in the role of the neurotransmitter serotonin
in the control of breathing. We have found that in male rats with
increasing age, serotonin levels decrease in areas of the brain
that help to keep the upper airway functioning normally. In contrast,
these changes are not seen in aging female rats. In other studies
on rats, we have recorded an age-associated decline in the normal
response to episodes of hypoxia in male rats. Once again, similar
changes were not seen in female rats. These data led us to conclude
that aging has a gender-specific effect on how serotonin can modulate
the respiratory control system. For
over a century it has been known that fluctuations in female hormone
levels associated with the estrus cycle and with pregnancy have
profound effects on breathing, and recent evidence supports a role
for the female gonadal hormones, estrogen and progesterone in the
neural control of breathing. The male gonadal hormone testosterone
may also be involved in the control of breathing, as it can be converted
to estrogen in the brain. Gonadal hormone levels decline with age.
We believe that there is a link between increasing age, levels of
gonadal hormones, serotonin, and the neural control of breathing.
Recent results from our laboratory show that levels of serotonin
in brain regions involved in the control of breathing fluctuate
during the rat estrus cycle, and decrease following gonadectomy.
The responses of the respiratory system to episodes of hypoxia also
change with hormone levels in both male and female rats. Taken together,
our data support the hypothesis that gonadal hormones play a critical
role in the maintenance of respiratory function with increasing
age through their action on the serotonergic system in the brain.
Preliminary studies suggest that manipulations of gonadal hormone
levels can reverse or delay the age-associated changes in the neural
control of breathing. These studies provide a better understanding
of the age and gender-related contributions of the serotonergic
system to sleep-associated breathing disorders such as obstructive
sleep apnea (OSA). OSA is an age-associated disease that is far
more prevalent in men than women, and also more prevalent in women
after menopause who are not taking hormone replacement therapy.
Related to This Topic:
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