Increased Expression of the Neuroregenerative Peptide Galanin in the Major Pelvic Ganglion Following Cavernous Nerve Injury

Abstract

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.

Lumbar spinal cord neurons putatively involved in ejaculation are sexually dimorphic in early postnatal mice

“…We also found many fluorescent DRG neurons (Figure ), a result consistent with the notion that galanin accumulation in pseudo‐unipolar neuron somas reaches a peak after birth (Marti et al, ) then decreasing to low levels in the adult (Xu, Shi, & Hökfelt, ). Interestingly, galanin expression in the ganglia can be markedly upregulated after injury (Xu et al, ), a phenomenon also occurring in the autonomic nervous system (Weyne et al, ).…”

Crosstalk between exercise and galanin system alleviates insulin resistance

“…Contrarily, the galanin knock-out postnatal mice showed significantly increase in the number of apoptotic cells in a subset of dorsal root ganglion neurons at postnatal day 3-4 as compared with wild controls (Holmes et al, 2000). Lastly, it has been demonstrated that galanin can promote regeneration of neurons, including proliferation and migration of cells in the peripheral and central nervous system (Vrontakis, 2002;Weyne et al, 2014). Approximate one-third of neurite out growth in dorsal root ganglion cultures is dependent on the tonic release of galanin in the adult rats after peripheral nerve injury (Holmes et al, 2000).…”

Beneficial effects of neuropeptide galanin on reinstatement of exercise‐induced somatic and psychological trauma

“…It has been demonstrated that galanin can promote proliferation, migration, nutrition, and regeneration of neurons in the peripheral and central nervous systems after injury (Vrontakis, ; Wilson‐Gerwing and Verge, ; Weyne et al, ). Approximately one‐third of neurite outgrowth in DRG cells was dependent on the galanin release after injury of the peripheral nerve in adult rats (Holmes et al, ).…”

“…It has been demonstrated that galanin can promote proliferation, migration, nutrition, and regeneration of neurons in the peripheral and central nervous systems after injury (Vrontakis, 2002;Wilson-Gerwing and Verge, 2006;Weyne et al, 2014). Approximately one- (Holmes et al, 2000).…”