PD62-03 SCHWANN CELL CO-CULTURE PROMOTES NEURITOGENESIS AND SURVIVAL IN IRRADIATED PELVIC NEURONS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (PD62)1 Sep 2021PD62-03 SCHWANN CELL CO-CULTURE PROMOTES NEURITOGENESIS AND SURVIVAL IN IRRADIATED PELVIC NEURONS Joshua Randolph, Elena Pak, Bridget Koontz, and Johanna Hannan Joshua RandolphJoshua Randolph More articles by this author , Elena PakElena Pak More articles by this author , Bridget KoontzBridget Koontz More articles by this author , and Johanna HannanJohanna Hannan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002099.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostatic radiation therapy (RT) damages the major pelvic ganglia (MPG) and nerves leading to erectile dysfunction (ED). Schwann cells (SCs) are known to facilitate neuron repair following mechanical injury, but their role in RT-induced neuron injury and repair has not been established. This study investigates the effects of co-culturing MPG neurons with SCs after ex vivo RT. METHODS: SCs were isolated by collecting MPGs from male Sprague-Dawley rats (n=12) which were digested in collagenase/dispase, and grown in SC medium. SCs were plated on poly-L lysine-coated coverslips and incubated to confluence for 24 hours. Confluent SCs were irradiated (0 or 8 Gy) prior to plating of neurons. Additional MPGs (n=18) were irradiated (0 or 8 Gy) and digested to isolate neurons. Dissociated neurons were plated alone or on SC-coated coverslips to create 6 experimental groups (n=3/grp): 1) CON MPG, 2) RT MPG, 3) CON SC+CON MPG, 4) RT MPG+CON SC, 5) CON MPG+RT SC, and 6) RT MPG+RT SC. After 72 hours, coverslips were fixed and stained for beta-tubulin (neuron marker), S100 protein (myelinating SC marker), neuronal nitric oxide synthase (nNOS; nitrergic marker), tyrosine hydroxylase (TH; sympathetic marker), and TUNEL to assess neurite length, branching, specific neuron populations and apoptosis. RESULTS: As previously demonstrated, ex vivo RT decreased MPG neuron length, increased apoptosis and decreased nitrergic neurons. In the current study, co-culturing RT MPG+CON SC increased neurite outgrowth compared to all other groups (p<0.001). Neurite branching was markedly reduced in the RT MPG+RT SC co-culture, but unchanged in other groups. The proportion of apoptotic neurons was markedly greater in RT MPG neurons, but when co-cultured with CON SC RT-induced neuronal apoptosis was prevented (p<0.01). The proportion of adrenergic TH positive neurons was unchanged while nitrergic neurons were significantly lower in RT neurons and co-culture with CON SCs was unable to prevent nitrergic loss. CONCLUSIONS: RT increases MPG neuron death and decreases pro-erectile nitrergic neurons. CON SC co-culture appears to stimulate neurite growth and restore branching networks in RT MPGs. While CON SCs significantly reduced apoptosis in RT MPG neurons, they were unable to prevent RT-induced nitrergic neuron loss. These data suggest that healthy SCs may promote survival and growth in RT-injured MPG neurons. Further in vivo studies are required to confirm whether administration or activation of SCs can help prevent RT-induced neuronal injury and ED. Source of Funding: Urology Care Foundation’s Herbert Brendler, MD., Summer Medical Student Fellowship; Sexual Medicine Society of North America, Research Grant © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1073-e1073 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Randolph More articles by this author Elena Pak More articles by this author Bridget Koontz More articles by this author Johanna Hannan More articles by this author Expand All Advertisement Loading ...