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Publication
Serotonin Receptor 5-HT3A Affects Development of Bladder Innervation and Urinary
Bladder Function.
Authors Ritter KE, Wang Z, Vezina CM, Bjorling DE, Southard-Smith EM
Submitted By Submitted Externally on 1/25/2018
Status Published
Journal Frontiers in neuroscience
Year 2017
Date Published
Volume : Pages 11 : 690
PubMed Reference 29311772
Abstract The autonomic and sensory nervous systems are required for proper function of
all visceral organs, including the lower urinary tract (LUT). Despite the wide
prevalence of bladder dysfunction, effective treatment options remain limited.
Pelvic innervation regenerative strategies are promising, but surprisingly
little is known about the molecular factors driving the development of bladder
innervation. Given prior evidence that serotonin receptor 5-HT3A is expressed
early in LUT development and is an important mediator of adult bladder function,
we sought to determine if 5-HT3A is required for the development of autonomic
innervation of the bladder. We found that 5-HT3A is expressed early in fetal
mouse pelvic ganglia and is maintained through adulthood. Htr3a knockout male
mice, but not females, exhibit increased urinary voiding frequency compared to
wild type littermates. Analysis of LUT function via anesthetized cystometry
revealed decreased voiding efficiency in male Htr3a mutants. Htr3a-/- mutant
animals exhibit a transient disturbance of autonomic neuronal subtype markers
(tyrosine hydroxylase and choline acetyl transferase) within the fetal pelvic
ganglia, although the imbalance of neuronal subtype markers assayed is no longer
apparent in adulthood. Loss of 5-HT3A activity results in a higher density of
autonomic and sensory neuronal fibers supplying bladder smooth muscle in both
fetal and adult mice. Collectively, our findings highlight 5-HT3A as a critical
component in the autonomic control of micturition and identify a novel role for
this serotonin receptor in peripheral nervous system development.




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