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The hypothesis guiding this research is that aging causes gender-specific structural, neurochemical and functional alterations in serotonergic modulation of respiratory motoneurons. There appears to be a selective decrease in serotonergic innervation of respiratory motoneurons with increasing age in male (but not female) rats, leading to functional deficits in respiratory motor output, particularly the output to upper airway muscles. Because of gender-related differences in the serotonergic modulation of the respiratory control system, aging males may be uniquely susceptible to sleep-associated breathing disorders.
Ongoing studys in the laboratory are testing the hypothesis that gonadal hormones have a neuroprotective role in the maintenance of serotonergic modulation of respiratory motoneurons in female rats, and can reverse or delay the age-associated changes in male rats. The results of these studies should 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. Specifically, the results may help explain why obstructive sleep apnea is more prevalent in men than in women, and increases dramatically in women following menopause.
Future work in the laboratory will explore the capacity for plasticity in respiratory control in aged male and female rats. We are particularily interested in the effects of chronic intermittent hypoxia. These studies will use physiological and molecular biological approaches.
Behan, M. and M. S. Brownfield. 1999 Age-related changes in serotonin in the hypoglossal nucleus of rat: Implications for sleep-disordered breathing. Neurosci. Lett. 267:133-136. [Abstract]
Fuller, D.D., Baker, T.L., Behan, M. and G.S. Mitchell, 2001.
Expression of hypoglossal long term facilitation differs between sub-strains of Sprague-Dawley rat. Physiol. Genomics 4;175-181 [Full text]Zabka, A.G., Behan, M. and G.S. Mitchell, 2001.
Long term facilitation (LTF) of phrenic and hypoglossal motor output decreases with age in male rats. J. Physiol. 531:509-514 [Full text ]Zabka, A.G., Behan, M. and G.S. Mitchell, 2001. Time dependent hypoxic respiratory responses in female rats are influenced by age and by the estrus cycle. J. Appl. Physiol. 91:2831-2838 [Full text]
Behan, M., Zabka, A.G., and G.S. Mitchell. 2002. Age and gender effects on serotonin-dependent plasticity in respiratory motor control. Respir. Physiol. and Neurobio. 131:65-77. [Abstract]
Behan, M., Zabka, A.G., Thomas, C.F., and G.S. Mitchell, 2003. Sex steroid hormones and the neural control of breathing. Respir. Physiology. and Neurobio. 136:249-263. [Abstract]
Behan, M., and C.F. Thomas. 2005. Sex hormone receptors are expressed in identified respiratory motoneurons in male and female rats. Neuroscience 130:725-734. [Abstract]
Zabka, A.G., Mitchell, G.S. and M. Behan. 2005. Aging and gonadectomy have similar effects on hypoglossal long-term facilitation in male Fisher rats. J. Physiol. Mar 1;563(Pt 2):557-68. [Abstract]
Zabka, A.G., Mitchell, G.S., and M. Behan. 2006. Conversion from testosterone to estradiol is required to modulates respiratory long-term facilitation in male rats. J. Physiol. 576: 903-912. [Abstract]
Seebart B.R., Stoffel, R. T. and M. Behan. 2007. Age-related Changes in the Serotonin 2A Receptor in the Hypoglossal Nucleus of Male and Female Rats. Resp. Phys. Neurobiol. 158: 14-21. [Abstract]
NIH RO1 AG18760
Dr. M. Behan (P.I.)
(2007 - 2012)
Age, Gender, Serotonin and Respiratory Control
NIMH RO1 DC008149
Dr. N. Connor (P.I.)
Dr. M. Behan (Co-I)
(2006 - 2011)
Aging, Exercise and Mechanisms of Altered Tongue Function
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Updated 06/29/2007