UNIVERSITY OF KENTUCKY
Grant: $33,413 - National Institutes of Health - May. 28, 2009
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Award Description: As individuals age, muscle weakness and neuromuscular disorders have the potential to diminish the quality of life, increase health care costs, and lead to institutionalization. The larynx is part of a complex motor system that serves dually as the vibratory source of phonation and as a valve that separates and protects the airway from the digestive tract. In the elderly, age-related changes in the intrinsic laryngeal muscles may compromise voice quality, thus, impair the ability to communicate and diminish the ability to remain socially engaged. Laryngeal dysfunction may also cause dysphagia and increase the risk of aspiration which may translate to higher mortality and morbidity. Our preliminary findings indicate that the intrinsic laryngeal muscles have a unique phenotype that is significantly altered by age; however, the biology of these small muscles remains largely unexplored. This project, in response to the NIDCD Small Grant (R03) Program, will achieve two objectives: (1) it will determine how age alters neuromuscular junction organization and function in the intrinsic laryngeal muscles; (2) it will provide a mechanism to further the professional development of the PI, leading to scientific independence. The studies will test the central hypothesis that aging disrupts the organization and stability of the neuromuscular junction in the intrinsic laryngeal muscles. Using the Fischer 344-Brown Norway F1 hybrid rat model of aging, the studies will examine to what extent aging alters NMJ organization in the posterior cricoarytenoid (PCA, vocal fold abductor) and thyroarytenoid (TA, vocal fold adductor) muscles. Three Specific Aims will be accomplished. Specific Aim 1 will test whether age changes NMJ ultrastructure and the expression of acetylcholine receptor subunits in the intrinsic laryngeal muscles. Specific Aim 2 will evaluate if aging represses cellular signaling pathways that initiate and sustain NMJ organization in the intrinsic laryngeal muscles. Specific Aim 3 will assess to what extent age alters the acetylcholine vesicle release system in the presynaptic terminals of the intrinsic laryngeal NMJs. This project will generate novel data on how age disrupts NMJ organization in the intrinsic laryngeal muscles, and will provide the bases for interventions aimed at preventing or reversing age-related neuromuscular dysfunction in these small muscles. In addition, the anticipated results will be of relevance to diseases not associated with aging but that affect NMJ structure and function such as myasthenia gravis and the Lambert- Eaton myasthenic syndrome.
Project Description: As defined in the Award Description field.Studies supported by the parent grant have demonstrated that the aging posterior cricoarytenoid (PCA) and thyroarytenoid (TA) become weaker and slower. Moreover neuromuscular junctions (NMJs) become smaller and less abundant in the aging rat laryngeal muscles. There is also functional evidence of denervation as aging PCA and TA become significantly more sensitive to neuromuscular transmission block. This project will be now extended to test the hypothesis that age related laryngeal muscle dysfunction is due to a decrease in cytoskeltal proteins necessary for muscle maintanence. Specific Aim I will examine the effect of age on the dystrophin -glycoprotein complex in rat PCA and TA muscles. This project will generate novel data on how aging induces the loss of cytoskeletal proteins in the intrinsic laryngeal muscles, and will provide insights into the mechanisms of neuromuscular and contractile dysfunction in these small muscles. The project also serves as an ideal short-term research experience for a science educator. The identified individual will develop new skills and ideas to take back to the classroom, enhancing science education and encouraging students to pursue research careers in health-related fields.
Jobs Summary: A Temporary Professional Non-Administrative (trainee) position was created for summer employment due to ARRA funds. This job will allow the middle school science school educator to incorporate his research experience into his middle school teaching. (Total jobs reported: 0)
Project Status: More than 50% Completed
This award's data was last updated on May. 28, 2009. Help expand these official descriptions using the wiki below.
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