TY - JOUR
T1 - Increased expression of the neuroregenerative peptide galanin in the major pelvic ganglion following cavernous nerve injury
AU - Weyne, Emmanuel
AU - Albersen, Maarten
AU - Hannan, Johanna L.
AU - Castiglione, Fabio
AU - Hedlund, Petter
AU - Verbist, Godelieve
AU - De Ridder, Dirk
AU - Bivalacqua, Trinity J.
AU - Van der Aa, Frank
N1 - Funding Information:
This study was supported in part by grant funding from the National Institutes of Health (K08DK090370). J.L.H. was funded Urology Care Foundation Research Fellowship and T.J.B the Urological Care Foundation Rising Star. MA and FC were funded by a Grant for Medical Research from the European Society of Sexual Medicine (ESSM). Further we would like to thank Xiaopu Liu for the excellent technical assistance.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2014/7
Y1 - 2014/7
N2 - Introduction: Erectile dysfunction (ED) remains a frequent complication of radical prostatectomy due to injury to the cavernous nerves (CNs). A recent microarray showed the neuropeptide galanin to be one of the most strikingly upregulated genes in the rat major pelvic ganglion (MPG) after bilateral CN crush injury (BCNI). Aim: The aim of this study is to evaluate the temporal regulation of galanin in the MPG after BCNI and its relationship to functional nerve regeneration. Methods: Changes in galanin, galanin receptor (galR), and c-JUN mRNA expression were assessed in Sprague-Dawley rats after sham operation (n=10) and at 48 hours (n=10), 7 (n=10), 14 (n=5), 21 (n=5), 30 (n=5), and 60 (n=5) days after BCNI using quantitative PCR. Erectile function was assessed by measuring intracavernous pressure (ICP) divided by mean arterial pressure (MAP) during CN electrostimulation. Immunohistochemistry was performed on the MPG in sham-operated animals and 5 days after BCNI. Main Outcome Measures: ICP/MAP upon CN stimulation; galanin, galR1, -2, -3, and c-JUN mRNA expression at various time points after BCNI; and nNOS, galanin, and galR distribution in the MPG of sham-operated rats and after BCNI. Results: After BCNI, ICP/MAP values quickly deteriorate, while after 60 days, spontaneous restoration of erectile responses to CN stimulation is observed, reflecting CN regeneration. Galanin mRNA in the MPG is up to 186-fold upregulated compared with sham-operated rats at 48 hours and 7 days after BCNI and gradually declines with increasing time from injury, whereas galanin receptor expressions decrease and c-JUN gradually increases. Galanin expression shows a strong inverse correlation with erectile responses to CN stimulation with time from injury. Injured MPGs show a colocalization between galanin- and nNOS-positive neuronal cell population in the MPG. Conclusions: Galanin is upregulated in the MPG in the early phase after CN injury after which it gradually decreases and is present in nNOS-positive neurons of the ganglion. We hypothesize that galanin upregulation is an important factor in the endogenous neuroregenerative response to CN injury.
AB - Introduction: Erectile dysfunction (ED) remains a frequent complication of radical prostatectomy due to injury to the cavernous nerves (CNs). A recent microarray showed the neuropeptide galanin to be one of the most strikingly upregulated genes in the rat major pelvic ganglion (MPG) after bilateral CN crush injury (BCNI). Aim: The aim of this study is to evaluate the temporal regulation of galanin in the MPG after BCNI and its relationship to functional nerve regeneration. Methods: Changes in galanin, galanin receptor (galR), and c-JUN mRNA expression were assessed in Sprague-Dawley rats after sham operation (n=10) and at 48 hours (n=10), 7 (n=10), 14 (n=5), 21 (n=5), 30 (n=5), and 60 (n=5) days after BCNI using quantitative PCR. Erectile function was assessed by measuring intracavernous pressure (ICP) divided by mean arterial pressure (MAP) during CN electrostimulation. Immunohistochemistry was performed on the MPG in sham-operated animals and 5 days after BCNI. Main Outcome Measures: ICP/MAP upon CN stimulation; galanin, galR1, -2, -3, and c-JUN mRNA expression at various time points after BCNI; and nNOS, galanin, and galR distribution in the MPG of sham-operated rats and after BCNI. Results: After BCNI, ICP/MAP values quickly deteriorate, while after 60 days, spontaneous restoration of erectile responses to CN stimulation is observed, reflecting CN regeneration. Galanin mRNA in the MPG is up to 186-fold upregulated compared with sham-operated rats at 48 hours and 7 days after BCNI and gradually declines with increasing time from injury, whereas galanin receptor expressions decrease and c-JUN gradually increases. Galanin expression shows a strong inverse correlation with erectile responses to CN stimulation with time from injury. Injured MPGs show a colocalization between galanin- and nNOS-positive neuronal cell population in the MPG. Conclusions: Galanin is upregulated in the MPG in the early phase after CN injury after which it gradually decreases and is present in nNOS-positive neurons of the ganglion. We hypothesize that galanin upregulation is an important factor in the endogenous neuroregenerative response to CN injury.
KW - Autonomic nerve regeneration
KW - C-JUN
KW - Cavernous nerve injury
KW - Galanin receptor
KW - Major pelvic ganglion
KW - Neurogenic erectile dysfunction
KW - Neuronal nitric oxide synthase
KW - Neuroregeneration
KW - Parasympathetic
KW - Radical prostatectomy
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U2 - 10.1111/jsm.12570
DO - 10.1111/jsm.12570
M3 - Article
C2 - 24831646
AN - SCOPUS:84903814278
VL - 11
SP - 1685
EP - 1693
JO - Journal of Sexual Medicine
JF - Journal of Sexual Medicine
SN - 1743-6095
IS - 7
ER -