Serotonin Receptor 5-HT3A Affects Development of Bladder Innervation and Urinary Bladder Function

Wang, Zunyi; Vezina, Chad M.; Bjorling, Dale E.; Southard‐Smith, E. Michelle

doi:10.3389/fnins.2017.00690

Cited by 17 publications

(20 citation statements)

References 49 publications

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“…Specifically, TF and K channels were upregulated in lumbar DRG, while LGIC, GPCR, NTFR, Ca, and TRP channels were upregulated in sacral DRG. One of the genes in the LGIC group (Htr3a) has been previously implicated in bladder sensory dysfunction (Ritter et al, 2017), but to our knowledge the various glutamate and GABA receptor transcripts upregulated in sacral DRG (Grin3a, Gabra3, Gabrg3) have not yet been examined in this context. LGIC receptors for the neurotransmitter acetylcholine showed a diverse expression pattern, with Chrna3 and Chrnb4 upregulated in sacral DRG, Chrna7 upregulated in lumbar DRG and other subunits not differentially expressed between spinal levels.…”

Section: Resultsmentioning

confidence: 99%

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Smith-Anttila

Mason

Wells

et al. 2020

eNeuro

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Visceral sensory neurons encode distinct sensations from healthy organs and initiate pain states that are resistant to common analgesics. Transcriptome analysis is transforming our understanding of sensory neuron subtypes but has generally focused on somatic sensory neurons or the total population of neurons in which visceral neurons form the minority. Our aim was to define transcripts specifically expressed by sacral visceral sensory neurons, as a step towards understanding the unique biology of these neurons and potentially leading to identification of new analgesic targets for pelvic visceral pain. Our strategy was to identify genes differentially expressed between sacral dorsal root ganglia (DRG) that include somatic neurons and sacral visceral neurons, and adjacent lumbar DRG that comprise exclusively of somatic sensory neurons. This was performed in adult and E18.5 male and female mice. By developing a method to restrict analyses to nociceptive Trpv1 neurons, a larger group of genes were detected as differentially expressed between spinal levels. We identified many novel genes that had not previously been associated with pelvic visceral sensation or nociception. Limited sex differences were detected across the transcriptome of sensory ganglia, but more were revealed in sacral levels and especially in Trpv1 nociceptive neurons. These data will facilitate development of new tools to modify mature and developing sensory neurons and nociceptive pathways.In this study of mouse dorsal root ganglia (DRG), we have identified numerous features of sensory neurons that vary between lumbar and sacral spinal levels and that are potentially involved in unique physiology and pathophysiology of visceral sensation and pain. We further identify maturational components of this sacral visceral transcriptome by comparing data from embryonic and adult mice. There are limited sex differences across the transcriptome of embryonic or adult sensory ganglia, but in adults these can be revealed in sacral levels and especially in Trpv1 nociceptive neurons. These datasets will encourage identification of new tools to modify mature or developing sensory neurons and adult nociceptive pathways.

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Section: Resultsmentioning

confidence: 99%

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Smith-Anttila

Mason

Wells

et al. 2020

eNeuro

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“…Anesthetized CMG. CMG was performed with minimal alterations to previously published protocols (4,34). Mice were anesthetized with urethane (1.43 g/kg sc).…”

Section: Methodsmentioning

confidence: 99%

Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment

Ruetten

Wegner

Zhang

et al. 2019

American Journal of Physiology-Renal Physiology

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Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of lower urinary tract symptoms. Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomic, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multiparameter “baseline” of voiding function in intact male and female 9-wk-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrated male mice, male (and female) mice treated with the steroid 5α-reductase inhibitor finasteride, or male mice harboring alleles ( Pbsn4cre/+; R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female mice) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male mice). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.

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“…If the experiment requires selective denervation by interruption of one or more nerves, it is recommended to ligate the severed nerve to prevent reinnervation and confounding of analyses. This dissection protocol could also be utilized for the mouse, where there is also an MPG with comparable function 26,27,28 .…”

Section: Discussionmentioning

confidence: 99%

Dissection of Pelvic Autonomic Ganglia and Associated Nerves in Male and Female Rats

Bertrand

Keast

2020

JoVE

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The bilateral major pelvic ganglia (MPG; synonym, pelvic ganglia) are the primary source of postganglionic sympathetic and parasympathetic neurons innervating pelvic organs of rodents; the functionally equivalent structure in humans is the inferior hypogastric plexus. The major pelvic ganglia also provide the route by which lumbar and sacral sensory axons reach the pelvic organs. These complex, mixed ganglia can prove challenging to identify and dissect for further experimental study of normal autonomic mechanisms or to establish preclinical models of disease, injury or visceral pain. Here we describe a protocol to access and visualize these ganglia and their associated nerve tracts. We provide this protocol with schematics for both male and female rats, as the ganglion size and landmarks for identification differ between sexes. The protocol describes removal of the ganglion for in vitro studies, but this method can be integrated into a surgical recovery protocol for experimental interventions (e.g., nerve crush, nerve resection) or for mapping neuronal circuits (e.g., by microinjection of neural tracers). We also demonstrate the primary structures of the ganglion and its associated nerves immediately following dissection and following immunohistochemical staining.

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Serotonin Receptor 5-HT3A Affects Development of Bladder Innervation and Urinary Bladder Function

Cited by 17 publications

References 49 publications

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Identification of a Sacral, Visceral Sensory Transcriptome in Embryonic and Adult Mice

Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment

Dissection of Pelvic Autonomic Ganglia and Associated Nerves in Male and Female Rats

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