Social-Stress-Induced Urinary Dysfunction: A Model of Dysfunctional Voiding
(PI, Rita J. Valentino, Ph.D.).
Dysfunctional voiding is a prevalent childhood disorder with potentially severe medical consequences and is also a cause of severe emotional and social distress. The lack of an animal model of dysfunctional voiding has hampered therapeutic advances in this area. In Project 1, we take advantage of the finding that rodents exposed to social stress, such as defeat in a conflict, develop bladder hypertrophy in the absence of an obstruction and so the characteristics and underlying mechanisms of social stress-induced bladder hypertrophy in rat may model dysfunctional voiding in children. The proposed experiments will characterize the urinary dysfunction associated with social stress at the functional and structural levels and compare this to the dysfunction produced by PBOO. The proposed studies will optimize behavioral aspects of the model and use in vivo cystometry to characterize and compare stress-induced urodynamic dysfunction with that produced by PBOO. In addition, by using electrophysiological recordings of specific neurons in the pontine micturition circuit and cortical electroencephalographic (EEG) recordings, we will determine whether alterations in brain-bladder communication produced by social stress contribute to the urinary dysfunction. Finally, we will use molecular and biochemical techniques to identify brain and/or bladder substrates that contribute to urinary dysfunction and bladder hypertrophy. Here our studies will integrate with those of other investigators in the Center, who investigate the cellular/ molecular basis of bladder remodeling in PBOO.