Developing a functional urinary bladder: a neuronal context

Abstract

The development of organs occurs in parallel with the formation of their nerve supply. The innervation of pelvic organs (lower urinary tract, hindgut, and sexual organs) is complex and we know remarkably little about the mechanisms that form these neural pathways. The goal of this short review is to use the urinary bladder as an example to stimulate interest in this question. The bladder requires a healthy mature nervous system to store urine and release it at behaviorally appropriate times. Understanding the mechanisms underlying the construction of these neural circuits is not only relevant to defining the basis of developmental problems but may also suggest strategies to restore connectivity and function following injury or disease in adults. The bladder nerve supply comprises multiple classes of sensory, and parasympathetic or sympathetic autonomic effector (motor) neurons. First, we define the developmental endpoint by describing this circuitry in adult rodents. Next we discuss the innervation of the developing bladder, identifying challenges posed by this area of research. Last we provide examples of genetically modified mice with bladder dysfunction and suggest potential neural contributors to this state.

Innervation of internal female genital organs in the pig during prenatal development

“…The current results correspond with observations concerning the development of the innervation of the urinary bladder in human foetuses (Keast et al. ), which revealed that DβH‐ or VAChT‐positive nerve structures appear much earlier than those expressing CGRP and/or SP (Keast et al. ).…”

“…), urinary bladder (Keast et al. ) and gut in human (Faussone‐Pellegrini et al. ) and urinary tract in the dog foetuses (Arrighi et al.…”

Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides

“…Bladder afferents contain a variety of neuropeptides, including: CGRP, Sub P, vasoactive intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide, cholecystokinin and enkephalins (Arms and Vizzard, 2011; de Groat et al, 1983; Keast and De Groat, 1992; Vizzard, 2000d, 2001). The innervation of the urinary bladder arises primarily from neuronal cell bodies located at a distance from the urinary bladder; however, some neuronal cell bodies appear transiently in the bladder wall during development and early postnatal life, with few remaining by adulthood (Keast et al, 2015; Zvarova and Vizzard, 2005). The functions of these intramural ganglion neurons are not known but their chemical phenotype more closely resembles autonomic rather than sensory neurons (Forrest et al, 2014; Keast et al, 2015; Zvarova and Vizzard, 2005).…”

“…The innervation of the urinary bladder arises primarily from neuronal cell bodies located at a distance from the urinary bladder; however, some neuronal cell bodies appear transiently in the bladder wall during development and early postnatal life, with few remaining by adulthood (Keast et al, 2015; Zvarova and Vizzard, 2005). The functions of these intramural ganglion neurons are not known but their chemical phenotype more closely resembles autonomic rather than sensory neurons (Forrest et al, 2014; Keast et al, 2015; Zvarova and Vizzard, 2005). …”

“…In addition, studies of the development of micturition reflexes may provide insights into the management of neurogenic disorders of micturition. For example, injuries or disorders of the adult spinal cord that lead to the reemergence of primitive functions (reflex voiding and incontinence), prominent during early development, may represent a return to early voiding patterns (de Groat et al, 1998; de Groat and Yoshimura, 2012; Keast et al, 2015). Thus, the study of the maturation of voiding reflexes not only has merit on its own but also has the potential to improve our understanding of OAB and neurogenic voiding disorders.…”