Neurotrophins in the Lower Urinary Tract: Becoming of Age

Barbara      Frias; Tiago      Lopes; Rui      Pinto; Francisco      Cruz; Celia      Duarte Cruz

doi:10.2174/157015911798376253

Abstract

The lower urinary tract (LUT) comprises a storage unit, the urinary bladder, and an outlet, the urethra. The coordination between the two structures is tightly controlled by the nervous system and, therefore, LUT function is highly susceptible to injuries to the neuronal pathways involved in micturition control. These injuries may include lesions to the spinal cord or to nerve fibres and result in micturition dysfunction. A common trait of micturition pathologies, irrespective of its origin, is an upregulation in synthesis and secretion of neurotrophins, most notably Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF). These neurotrophins are produced by neuronal and non-neuronal cells and exert their effects upon binding to their high-affinity receptors abundantly expressed in the neuronal circuits regulating LUT function. In addition, NGF and BDNF are present in detectable amounts in the urine of patients suffering from various LUT pathologies, suggesting that analysis of urinary NGF and BDNF may serve as likely biomarkers to be studied in tandem with other factors when diagnosing patients. Studies with experimental models of bladder dysfunction using antagonists of NGF and BDNF receptors as well as scavenging agents suggest that those NTs may be key elements in the pathophysiology of bladder dysfunctions. In addition, available data indicates that NGF and BDNF might constitute future targets for designing new drugs for better treatment of bladder dysfunction.

Keywords: NGF, BDNF, Trk receptors, bladder, LUT, NEUROTROPHINS (NTs), Brain-Derived Neurotrophic Factor (BDNF), NTs family, NERVE GROWTH FACTOR (NGF)