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Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury
Journal article   Open access   Peer reviewed

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

Shaoping Hou, David M Carson, Di Wu, Michelle C Klaw, John D Houlé and Veronica J Tom
Experimental neurology, v 285(Pt B)
Nov 2016
DOI: https://doi.org/10.1016/j.expneurol.2015.12.001
PMID: 26655672
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc4889553View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Animals Animals, Newborn Choline O-Acetyltransferase - metabolism Disease Models, Animal Dopamine - analogs & derivatives Dopamine - metabolism Dopamine Agents - pharmacology Enzyme-Linked Immunosorbent Assay Female Ganglia, Parasympathetic - pathology Ganglia, Sympathetic - pathology Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Herpesvirus 1, Suid - genetics Herpesvirus 1, Suid - metabolism Neurons - metabolism Oxidopamine - toxicity Rats Rats, Inbred F344 Rats, Sprague-Dawley Rats, Wistar Reflex - physiology Spinal Cord - metabolism Spinal Cord - physiopathology Spinal Cord Injuries - chemically induced Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology Stilbamidines - pharmacokinetics Thiocarbamates - metabolism Transduction, Genetic Tyrosine 3-Monooxygenase - metabolism Urinary Bladder - innervation Urinary Bladder - physiopathology
Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH) neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH) and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D -like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI.

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35 citations in Web of Science
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Web of Science research areas
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