Whole genome microarray of the major pelvic ganglion after cavernous nerve injury: new insights into molecular profile changes after nerve injury.
What's known on the subject? and What does the study add? With the present study, we aimed to provide a global picture of the molecular processes that are activated by CN injury. The present study used genomic expression profiling to identify candidate genes that might be useful targets in the CN recovery process and, thus, the ultimate preservation of penile erection. Regeneration of the CN and axonal outgrowth clearly involve changes in multiple biochemical pathways that have never been investigated by microarray analysis. We analyzed global gene expression in the major pelvic ganglion at early stages (48 h and 14 days) after CN injury and focused on the detection of changes in genes related to nervous tissue repair and proliferation. The findings of the present study provide important insight into the molecular systems affected by CN injury and identify candidate genes that may be utilized for novel molecular-based therapies for the preservation and protection of the CN during RP.


OBJECTIVE
To to examine the complexity of the many molecular systems involved in supporting cavernous nerve (CN) repair and regeneration in a rat model of bilateral crush injury utilizing a microarray analysis approach. Erectile dysfunction (ED) is a common clinical complication after prostate cancer treatment by radical prostatectomy, and recovery of erectile function can take as long as 2 years. There are gaps in our understanding of the autonomic pelvic innervation of the penis that still need to be addressed for the development of an adequate treatment strategy for post-prostatectomy ED. The molecular mechanisms of the intrinsic ability of CN to regenerate after an injury have not been elucidated.


METHODS
We analyzed global gene expression in the major pelvic ganglion 48 h and 14 days after CN injury. Overall, a comparative analysis showed that 325 genes changed at the 48-h time point and 114 genes changed at 14 days. There were 60 changed genes in common with both time points. Using the Ingenuity Pathway Analysis® system (Ingenuity Systems, Inc., Redwood City, CA, USA), we were able to analyze the significantly changed genes that were unique and common to each time point by biological function. We focused on the detection of changes related to nervous tissue repair and proliferation, molecular networks of neurotrophic factors, stem cell regulation and synaptic transmission.


RESULTS
There was strong evidence of the early mobilization of genes involved in repair and neuroprotection mechanisms (SERPINF1, IGF1, PLAU/PLAUR, ARG1). Genes related to nervous system development (ATF3 GJA1, PLAU, SERPINE1), nerve regeneration (SERPINE2, IGF1, ATF3, ARG1) and synaptic transmission (GJC1, GAL) were changed. Several genes related to proliferation as well as apoptosis (A2M, ATF3, C3, EGR4, FN1, GJA1, GAL) were also changed, possibly as part of a protective mechanism or the initiation of remodelling.


CONCLUSIONS
The results obtained show that multiple biological processes are associated with injury and repair of the CN and provide a systematic genome-wide screen for neurotrophic and/or inhibitory pathways of nerve regeneration. These data identify the candidate genes that may be utilized in novel molecular-based therapies for the preservation and protection of the CN during radical prostatectomy.
Albert Einstein College of Medicine, Bronx, NY, USA.
Giulia
G
Calenda
Travis D
TD
Strong
Christian P
CP
Pavlovich
Edward M
EM
Schaeffer
Arthur L
AL
Burnett
Wayne
W
Yu
Kelvin P
KP
Davies
Trinity J
TJ
Bivalacqua
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005724:Ganglia / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D007001:Hypogastric Plexus / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009416:Nerve Regeneration / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010410:Penile Erection; D010413:Penis / Q000293:injuries / Q000294:innervation* / Q000378:metabolism; D012313:RNA / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020196:Trauma, Nervous System / Q000150:complications / Q000378:metabolism / Q000503:physiopathology
D015415:Biomarkers; D012313:RNA