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40 Neurite outgrowth of pelvic neurons is stimulated by the neurotrophic peptide galanin
Title
40
Neurite outgrowth of pelvic neurons is stimulated by the neurotrophic peptide galanin Eur Urol Suppl 2015;14/2;e40
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Weyne E. 1 , Hannan J.L. 2 , Liu X. 2 , De Ridder D.1 , Van Der Aa F.1 , Bivalacqua T.J.2 , Albersen M. 1 1 University
of Leuven, Dept. of Urology, Dept. of Development and Regeneration, Leuven, Belgium, 2 Johns Hopkins Medical Institutions,
James Buchanan Brady Urological Institute, Department of Urology, Baltimore, United States of America INTRODUCTION & OBJECTIVES: Erectile dysfunction remains a frequent sequela of radical prostatectomy (RP) due to neuropraxia of the cavernous nerves(CNs). Peripheral nerve regeneration is stimulated by the release of endogenous neurotrophic factors. Galanin is a neurotrophic factor transcriptionally upregulated 180-fold in major pelvic ganglions (MPG’s) of CN injured rats and also present in human CNs. Galanin has been shown to increase neurite outgrowth in sensory neurons mediated by galanin receptor 2 (galR2). In this study we investigate whether stimulation or inhibition of the galanin pathway influences regeneration of pelvic nerves in vitro. MATERIAL & METHODS: Major pelvic ganglion (MPG) and the CN were isolated from control and bilateral CN crush rats 48hrs after injury and subsequently cultured as a whole-mount explant in matrigel (Figure 1). Control MPGs were treated with culture medium(control), galanin (non-selective agonist) and M1145 (selective galR2-agonist). Injured MPGs were treated with culture medium (control), M40 (nonselective antagonist) and M871 (selective galR2-antagonist). Neurite outgrowth was measured in both experiments after 48hrs and 72hrs in culture. ANOVA was used to analyse differences in neurite outgrowth between treatments.
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/40.html[19/02/2015 08:12:39]
Title
RESULTS: Mean neurite outgrowth of MPGs from control animals showed a trend towards increased outgrowth with selective galR2-agonist treatment compared to control treatment (48h:453μm vs 367μm; 72h: 586μm vs 529μm; p>0.05). Inhibition of the galanin pathway in MPGs of injured rats with a selective galR2-antagonist resulted in decreased neurite outgrowth compared to control treatment (48h: 453μm vs 632μm; 72h: 477μm vs 708μm; p<0,05,p<0,01) (Figure 2) and this was more more pronounced than non-specific galanin inhibition. (48h: 607 μm vs 452 μm; p<0,05).
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/40.html[19/02/2015 08:12:39]
Title
CONCLUSIONS: Inhibition of the galanin pathway in pelvic ganglion neurons resulted in decreased neurite outgrowth, whereas galanin stimulation increased neurite outgrowth in vitro. The neurotrophic action of galanin is mediated through galR2. Galanin is an important component of endogenous CN regeneration and strategies increasing galanin production could be advantageous in EF recovery following RP.
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/40.html[19/02/2015 08:12:39]
40
Neurite outgrowth of pelvic neurons is stimulated by the neurotrophic peptide galanin Eur Urol Suppl 2015;14/2;e40
Print! Print!
Weyne E. 1 , Hannan J.L. 2 , Liu X. 2 , De Ridder D.1 , Van Der Aa F.1 , Bivalacqua T.J.2 , Albersen M. 1 1 University
of Leuven, Dept. of Urology, Dept. of Development and Regeneration, Leuven, Belgium, 2 Johns Hopkins Medical Institutions,
James Buchanan Brady Urological Institute, Department of Urology, Baltimore, United States of America INTRODUCTION & OBJECTIVES: Erectile dysfunction remains a frequent sequela of radical prostatectomy (RP) due to neuropraxia of the cavernous nerves(CNs). Peripheral nerve regeneration is stimulated by the release of endogenous neurotrophic factors. Galanin is a neurotrophic factor transcriptionally upregulated 180-fold in major pelvic ganglions (MPG’s) of CN injured rats and also present in human CNs. Galanin has been shown to increase neurite outgrowth in sensory neurons mediated by galanin receptor 2 (galR2). In this study we investigate whether stimulation or inhibition of the galanin pathway influences regeneration of pelvic nerves in vitro. MATERIAL & METHODS: Major pelvic ganglion (MPG) and the CN were isolated from control and bilateral CN crush rats 48hrs after injury and subsequently cultured as a whole-mount explant in matrigel (Figure 1). Control MPGs were treated with culture medium(control), galanin (non-selective agonist) and M1145 (selective galR2-agonist). Injured MPGs were treated with culture medium (control), M40 (nonselective antagonist) and M871 (selective galR2-antagonist). Neurite outgrowth was measured in both experiments after 48hrs and 72hrs in culture. ANOVA was used to analyse differences in neurite outgrowth between treatments.
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/40.html[19/02/2015 08:12:39]
Title
RESULTS: Mean neurite outgrowth of MPGs from control animals showed a trend towards increased outgrowth with selective galR2-agonist treatment compared to control treatment (48h:453μm vs 367μm; 72h: 586μm vs 529μm; p>0.05). Inhibition of the galanin pathway in MPGs of injured rats with a selective galR2-antagonist resulted in decreased neurite outgrowth compared to control treatment (48h: 453μm vs 632μm; 72h: 477μm vs 708μm; p<0,05,p<0,01) (Figure 2) and this was more more pronounced than non-specific galanin inhibition. (48h: 607 μm vs 452 μm; p<0,05).
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/40.html[19/02/2015 08:12:39]
Title
CONCLUSIONS: Inhibition of the galanin pathway in pelvic ganglion neurons resulted in decreased neurite outgrowth, whereas galanin stimulation increased neurite outgrowth in vitro. The neurotrophic action of galanin is mediated through galR2. Galanin is an important component of endogenous CN regeneration and strategies increasing galanin production could be advantageous in EF recovery following RP.
file:///S|/IM/EURSUP/2015%20EAU%20Abstracts/content/data/40.html[19/02/2015 08:12:39]