With the increase in the average age of the population, there has been an increase in the number of people with balance disorders. Along with this occurrence has been an increasing awareness of the importance of the vestibular system for human well being. Our understanding of vestibular disorders is generally limited by a lack of knowledge about the function of the vestibular system. Foundational to the function of any system is its underlying chemical composition. For a part of the nervous system, this includes the chemistry of intercellular communication, via neurotransmitters, as well as the chemistry of energy metabolism and cell structure. One way to gain insight about a system is to look at its response to injury. This is of particular interest for the vestibular system because of its plasticity observed in clinical situations. It is well known that destruction of the peripheral vestibular sense organ leads immediately to loss of the ability to maintain balance, but that over time the function returns. Despite much study of this phenomenon, the underlying mechanisms remain unknown. It is our belief that a lack of systematic chemical information about the vestibular system seriously impairs reaching an understanding of vestibular compensation. We have therefore undertaken a detailed systematic study of the underlying chemistry of the vestibular system and its changes during vestibular compensation. The major focus of the study is the vestibular nuclear complex because of its pivotal position in all vestibular function. We have begun by examining amino acid chemistry, which is critical for normal brain function and includes probably the major neurotransmitters of the brain, glutamate and gamma-aminobutyrate. There is already evidence that these two transmitters have important functions in the vestibular nuclear complex. Our methods include measurement of amino acid concentrations in the vestibular nuclear complex and vestibulocerebellum and use of three methods to particularly examine glutamate and GABA receptors: receptor binding autoradiography, immunohistochemistry, and in situ hybridization. In addition, we propose to make a start at examining intracellular mechanisms of neuronal interactions by examining the changes of GAP-43 protein, a marker for some aspects of neuronal plasticity, during vestibular compensation. Finally, for comparison to the neurotransmitter changes, we propose to examine energy metabolism during vestibular compensation by measuring activity of a key enzyme of oxidative energy metabolism, malate dehydrogenase.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
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Special Emphasis Panel (ZDC1-SRB-S (03))
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University of Toledo
Schools of Medicine
United States
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Godfrey, Donald A; Sun, Yizhe; Frisch, Christopher et al. (2012) Depolarization-induced release of amino acids from the vestibular nuclear complex. Neurochem Res 37:732-9
Sun, Yizhe; Godfrey, Donald A; Godfrey, Matthew A et al. (2011) Changes of amino acid concentrations in the rat vestibular nuclei after midline lesions. J Vestib Res 21:175-91
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Godfrey, Donald A; Xu, Jiansong; Godfrey, Matthew A et al. (2004) Effects of unilateral vestibular ganglionectomy on glutaminase activity in the vestibular nerve root and vestibular nuclear complex of the rat. J Neurosci Res 77:603-12
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Sun, Yizhe; Godfrey, Donald A; Rubin, Allan M (2002) Plasticity of gamma-aminobutyrate receptors in the medial vestibular nucleus of rat after inferior cerebellar peduncle transection. J Vestib Res 12:1-14
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Li, H; Godfrey, D A; Rubin, A M (1999) Astrocyte reaction in the rat vestibular nuclei after unilateral removal of Scarpa's ganglion. Ann Otol Rhinol Laryngol 108:181-8

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