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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Methods and Model Organisms
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1497735
This article is part of the Research Topic Multi-modality tools and applications in functional and mechanistic exploration in nervous systems View all 4 articles

Sensory innervation in the prostate and a role for calcitonin gene-related peptide in prostatic epithelial proliferation

Provisionally accepted
Hanyu Xia Hanyu Xia 1,2Travis J Jerde Travis J Jerde 1,2Jill C Fehrenbacher Jill C Fehrenbacher 1,2,3,4,5*
  • 1 Department of Pharmacology and Toxicology, School of Medicine, Indiana University Bloomington, Indianapolis, Indiana, United States
  • 2 Melvin and Bren Simon Comprehensive Cancer Center, Department of Medicine, School of Medicine, Indiana University Bloomington, Indianapolis, Indiana, United States
  • 3 School of Medicine, Indiana University Bloomington, Indianapolis, Indiana, United States
  • 4 Indiana Center for Musculoskeletal Health, Department of Medicine, School of Medicine, Indiana University Bloomington, Indianapolis, Indiana, United States
  • 5 Stark Neurosciences Research Institute, School of Medicine, Indiana University Bloomington, Indianapolis, Indiana, United States

The final, formatted version of the article will be published soon.

    The prostate is densely innervated like many visceral organs and glands. However, studies to date have focused on sympathetic and parasympathetic nerves and little attention has been given to the presence or function of sensory nerves in the prostate. Recent studies have highlighted a role for sensory nerves beyond perception of noxious stimuli, as anterograde release of neuropeptides from sensory nerves can affect vascular tone and local immune responses. To identify the degree of sensory innervation in the prostate, we utilized state-of-the-art tissue clearing and microscopy to visualize sensory innervation in the different lobes of the mouse prostate. To determine whether sensory nerves have a role in regulating proliferation within the prostate, we used an intersectional genetic and toxin approach to ablate peptidergic sensory nerves systemically. We found that sensory neurons are abundant in the prostate both in nerve bundles along the vasculature and as independent nerve fibers wrapped around prostatic acini in a net-like fashion. In addition to the dense innervation of the prostate, we found that Calca haploinsufficiency, the genotype control for our intersectional ablation model, results in a diminished level of Ki67 staining in the stromal compartment of the dorsal lobe and a diminishing Ki67 trend in other lobes. These findings suggest that sensory neurons might have developmental or homeostatic effects within the prostate. Further studies are warranted to assess the role of sensory neurons and the sensory neuropeptides on prostatic development and on proliferation in the presence of pro-inflammatory stimuli such as bacterial infection or tumor cells.

    Keywords: Prostate, Sensory nerve, Neuropeptide, epithelial proliferation, tissue clearing and labeling technique, Calcitonin gene-related peptide (CGRP)

    Received: 17 Sep 2024; Accepted: 28 Nov 2024.

    Copyright: © 2024 Xia, Jerde and Fehrenbacher. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jill C Fehrenbacher, School of Medicine, Indiana University Bloomington, Indianapolis, 46202, Indiana, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.