Case Western Reserve University
Grant: $400,620 - National Institutes of Health - Jul. 16, 2009
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Award Description: In response to changing afferent input, neural pathways may undergo both short term (minutes) and long term (days, weeks) adjustments within the pathway in order to maintain physiological output within an appropriate range. The underlying cellular mechanisms responsible for this homeostatic adaptation are generally unknown but may include changes in gene expression and subsequent protein distribution/function. In this study four independent research groups are bringing their collective expertise in different areas to a collaboration to define the mechanisms that underlie the long term changes in the central neural component of a cardio-respiratory reflex response to chronic intermittent hypoxia (CIH), a model of sleep apnea. We are using a combination of electrophysiological, molecular, genetic and imaging techniques to understand the adaptations (over days/weeks) to CIH that produce sustained changes in chemosensory synaptic transmission in the nucleus of the solitary tract leading to an elevated level of information transfer that is partially restrained by what we propose is a secondary homeostatic adaptation. These changes are thought to contribute to elevated arterial pressure and exaggerated chemoreflexes in CIH. We believe this study is important not only because it provides insight to potential mechanisms for manipulating respiratory and cardiovascular reflexes at specific sites but also because it provides insight to adaptations in neuronal transmission that may be universal in application. This study is designed to understand the changes that occur in the nervous system that may cause a patient with sleep apnea to develop hypertension and exaggerated hypoxic respiratory responses.
Project Description: We are asking how sleep apnea affects our ability to regulate respiration, blood pressure and heart rate. We are using a rat that is intermittently exposed to hypoxia as a model for sleep apnea. We have found that after 10 days of intermittent hypoxia, changes occur in regions of the brain that regulate blood pressure and breathing. Some (but not all) of these changes occur as early as three days. We propose that changes include an increase in the number of calcium channels in neurons that sense the low oxygen which may lead to, among other changes, hypertension. In the first quarter of this study we have identified using several different techniques, several specific types of calcium channels in the oxygen sensing neurons. We are now attempting to modify these to determine whether they are responsible for increased transmitter release.
Jobs Summary: Not Applicable (Total jobs reported: 0)
Project Status: Less Than 50% Completed
This award's data was last updated on Jul. 16, 2009. Help expand these official descriptions using the wiki below.
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