Browsing by Subject "Calcitonin Gene-Related Peptide (CGRP)"

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    Understanding the Structure-Function Relationship of Peptidergic Sensory Nerves in the Prostate
    (2024-12) Xia, Hanyu; Jerde, Travis J.; Fehrenbacher, Jill C.; Yeh, Elizabeth S.; Fishel, Melissa L.; Pierchala, Brian A.
    The prostate, like many other organs, is densely innervated. However, studies to date have largely focused on sympathetic and parasympathetic nerves with little attention given to the presence or function of sensory nerves in the prostate. Recent studies have suggested that the physiological function of sensory innervation extends beyond the detection of noxious stimuli, as anterograde release of neuropeptides from sensory nerves can affect vascular tone and local immune responses. Still, the broader role of peptidergic sensory innervation of the prostate remains unknown, and the research described herein fills this void in current prostate knowledge. Utilizing state-of-the-art tissue clearing and 3D immunofluorescence imaging, this study provides unprecedented visualizations of prostatic innervation, revealing an extensive network of peptidergic sensory nerves throughout the mouse prostate. Sensory nerves were observed in abundance accompanying vasculature and as independent nerve fibers wrapped around prostatic acini in a net-like fashion. To investigate the functional significance of this newly revealed sensory network, an intersectional genetic approach was employed to ablate peptidergic sensory nerves systemically. We found that Calca haploinsufficiency, the genotype control for the ablation model, diminished proliferating cells as determined by K-i67 positivity in the stromal compartment of the dorsal lobe and trended to decrease proliferation in other lobes. These findings suggest that sensory neurons might have developmental or homeostatic effects within the prostate. This work establishes a new foundation for understanding the complex roles of sensory innervation in normal prostate function and in prostatic diseases. Further studies are warranted to assess the role of sensory neurons and their neuropeptides on prostatic development and on proliferation in the presence of pro-inflammatory stimuli such as bacterial infection or tumor cells, which could lead to innovative approaches in prostate health management.