Untitled Document

Research

Mary Behan

Ph.D., University College Dublin, Ireland
Professor, Dept. of Comparative Biosciences
Associate Dean for Research & Graduate Training, School of Veterinary Medicine,
behanm@svm.vetmed.wisc.edu
http://www.vetmed.wisc.edu/people/behanm

The Role of Age and Gender in the Neural Control of Breathing

My research involves how aging effects the neural control of breathing. Very 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.

I 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. In males, testosterone may also play a role in the control of breathing as it can be converted to estrogen in the brain. Levels of gonadal hormones decline with age. We hypothesize that age-associated decreases in gonadal hormones can have a negative impact on the control of breathing, especially in response to respiratory challenges such as people experience in 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.

Recently we have begun to study the role of tongue muscle exercise in preventing the age-associated changes that take place in brain regions that are involved in upper airway patency during breathing and swallowing. We hypothesize that tongue exercise augments serotonergic modulation of respiratory motoneurons, and can thereby improve airway patency in the elderly.

Representative Publications
Barker, J., Thomas, C.F., & Behan, M. (In Press) Serotonergic input to the hypoglossal nucleus in male and female rats. Resp. Phys. Neurobiol.

Schwarz, E.C., Thompson, J. M., Connor, N.P., & Behan, M. (2009). The effects of aging on hypoglossal motoneurons in rats. Dysphagia, 24(1), 40-48.

Behan, M., & Wenninger, J. (2008). Sex hormones and modulation of respiratory motoneurons. Resp. Phys. Neurobiol., 164, 213-221.

Sample, S.J., Behan, M., Smith, L., Oldenhoff, W.E., Markel, M.D., Kalscheur, V.L., Hao, Z., Miletic, V., & Muir, P. (2008). Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones. J. Bone Miner. Res., 23, 1372-1381.

Seebart, B.R., Stoffel, R.T., & Behan, M. (2007). Age-related changes in the serotonin 2A receptor in the hypoglossal nucleus of male and female rats. Resp. Phys. Neurobiol., 158(1), 14-2.

Behan, M., & Thomas, C.F. (2005). Sex hormone receptors are expressed in identified respiratory motoneurons in male and female rats. Neuroscience, 130, 725-734.

Behan, M., Zabka, A.G., Thomas, C.F., & Mitchell., G.S. (2003). Sex steroid hormones and the neural control of breathing. Respiration Physiology and Neurobiology, 136, 249-263.

Zabka, A.G., Mitchell, G.S., Olson, Jr., E.B., & Behan, M. (2003). Chronic intermittent hypoxia enhances respiratory long term facilitation in geriatric female rats. J. Appl. Physiol., 95, 2614-2623.

Behan, M., Zabka, A.G., & Mitchell, G.S. (2002). Age and gender effects on serotonin-dependent plasticity in respiratory motor control. Respiration Physiology & Neurobiology, 131, 65-77.

Fuller, D.D., Baker, T.L., Behan, M., & Mitchell, G.S. (2001). Expression of hypoglossal long term facilitation differs between sub-strains of Sprague-Dawley rat. Physiol. Genomics, 4, 175-181.

Meredith, M.A., Miller, L.F., Ramoa, A.S., Clemo, H.R.H., & Behan, M. (2001). Organization of neurons of origin of the descending output pathways from the ferret superior colliculus. Neurosci. Res., 40, 301-313.

Parsons, M.J., Benca, R.M., Brownfield, M.S., & Behan, M. (2001). Age-associated changes in the serotonergic system in rat superior colliculus and pretectum. Brain Res. Bull., 55, 435-444.

Zabka, A.G., Behan, M., & Mitchell, G.S. (2001). Long term facilitation (LTF) of phrenic and hypoglossal motor output decreases with age in male rats. J. Physiol., 531, 509-514.

Zabka, A.G., Behan, M., & Mitchell, G.S. (2001). Time dependent hypoxic respiratory responses in female rats are influenced by age and by the estrus cycle. J. Appl. Physiol., 91, 2831-2838.

Behan, M., & Haberly, L.B. (1999). Intrinsic and efferent connections of the endopiriform nucleus in rat. J. Comp. Neurol., 408, 532-548.

Behan, M., & Brownfield, M.S. (1999). Age-related changes in serotonin in the hypoglossal nucleus of rat: Implications for sleep-disordered breathing. Neurosci. Lett., 267, 133-136.

Miller, A.M., Obermeyer, W.H., Behan, M., & Benca, R.M. (1998). Effects of superior colliculus-pretectal lesions on sleep: a novel site for mediating light induced sleep-behaviors. Proc. Natl. Acad. Sci., 95, 8957-8962.

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