BLADDER OUTLET OBSTRUCTION INDUCED NEUROPLASTICITY

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DESCRIPTION (provided by applicant) Benign prostatic hyperplasia (BPH) is the most common cause of bladder outflow obstruction (BOO). This condition is commonly associated with uninhibited urinary bladder contractions. Irritative voiding symptoms, a consequence of uninhibited bladder contractions are very bothersome to a large population of aging men, adversely affecting their quality of life. The overall hypothesis for this research proposal is that the marked changes in the neural control of voiding function that occur following BPH are mediated by multiple factors, including: (1) changes in the properties of urinary bladder afferent neurons induced by peripheral organ (bladder) dysfunction and (2) changes in the properties of interneuronal populations in the spinal cord. Thus, we propose that reorganization of spinal micturition circuitry occurs in response to changes in neural-target organ interactions. We plan to examine the effects of BOO on the neurochemical, organizational and morphological properties of afferent and spinal neurons involved in the micturition reflex pathway. This research proposal aims to provide a more thorough understanding of the wiring diagram for lower urinary tract reflexes and the functions of neurotransmitters in these reflexes. In the first part of our study we will assess neurochemical changes in neurons involved in the micturition reflex that project to the periphery following BOO. Peripheral and spinal neurons projecting to the bladder will be identified following injection of the tracer into the urinary bladder. Subsequently, immunohistochemical techniques will be used to determine changes in the expression of neuroactive compounds in these neurons. A second group of experiments will use pharmacological techniques to evaluate the role of neuroactive compounds in the central micturition pathway following chronic BOO. The effect of selective inhibitors of these neuroactive compounds on the micturition reflexes following BOO and in sham-operated controls will be determined with the use of the cystometrography (recording pressure changes in the urinary bladder during filling and micturition). In the third part of this research project, we propose to determine the organization of urinary bladder interneurons and parasympathetic preganglionic neurons in the. lumbosacral spinal cord. Changes in connectivity between the various spinal elements will be assessed following BOO.