Overactive bladder phenotype induced by chronic activation of hypothalamic neuroendocrine stress pathways in rats...

Overactive urinary bladder (OAB) negatively impacts quality of life, and stress is known to play a key role in its development. However, the mechanisms linking stress to OAB are not yet fully understood. This study examined how chronic activation of neuroendocrine stress pathways, independently of environmental or psychological stressors, affects bladder function and the control of micturition. Utilizing the central role of brain-derived-neurotrophic factor (BDNF) in orchestrating the neuroendocrine stress response within the paraventricular nucleus of the hypothalamus (PVN), our novel experimental model subjected 10-week-old male Sprague Dawley rats to bilateral PVN injections of AAV2 viral vectors expressing either BDNF or GFP (for control). Urine voiding behavior was assessed in UroVoid metabolic cages over 14 weeks post-injections. Bladder strip myography, assessment of bladder wall mechanics, and histology were also conducted to determine any BDNF-induced differences in bladder contractility, capacity and morphology. Prolonged activation of neuroendocrine stress mechanisms with BDNF overexpression in the PVN significantly reduced intermicturition intervals and voided volumes, lowered bladder capacity, and induced relative bladder wall hypertrophy but had no effect on bladder wall mechanics or detrusor contractility. These results indicate that chronic activation of neuroendocrine stress pathways, even without additional environmental or psychological influences of stress, lead to a significant OAB phenotype and reduced bladder capacity.