You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research I1 Apr 2012811 CAVERNOUS NERVE INJURY INCREASES STORE OPERATED CALCIUM CHANNELS AND APOPTOTIC MARKERS IN THE MAJOR PELVIC GANGLION Johanna L. Hannan, Omer Kutlu, Xiaopu Liu, Arthur L. Burnett, Petter Hedlund, and Trinity J. Bivalacqua Johanna L. HannanJohanna L. Hannan Baltimore, MD More articles by this author , Omer KutluOmer Kutlu Baltimore, MD More articles by this author , Xiaopu LiuXiaopu Liu Baltimore, MD More articles by this author , Arthur L. BurnettArthur L. Burnett Baltimore, MD More articles by this author , Petter HedlundPetter Hedlund Lund, Sweden More articles by this author , and Trinity J. BivalacquaTrinity J. Bivalacqua Baltimore, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.900AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The mechanism of neurodegeneration following radical prostatectomy remains unknown. Neuropraxia can result in “calcium overload” of intracellular stores and initiate neuronal cell death. Store-operated calcium (SOC) channels, such as STIM and Orai, are responsible for the replenishment of calcium stores following depletion and have been implicated in neurodegenerative diseases such as stroke. We hypothesize that cavernous nerve injury leads to increased expression of STIM and Orai which contributes to excess intracellular calcium leading to neuronal cell death. The purpose of this study was to: 1) characterize the time course of changes in STIM and Orai isoforms, and 2) apoptotic markers in the major pelvic ganglion (MPG), and correlate with in vivo erectile responses to cavernous nerve stimulation (CNS) after cavernous nerve injury (CNI). METHODS Male Sprague-Dawley rats (8-10wks) were divided into the following groups: sham or 48 hours, 7, 14, or 30 days after bilateral CNI (n=10/group). In vivo erectile responses to CNS, MPG protein expression via Western blots of STIM 1, 2 and Orai 1, 2, 3 and MPG gene expression by quantitative real-time polymerase chain reaction of STIM 1, 2, Orai 1, 2, 3 and caspase 1, 3 were evaluated following CNI at specified time points. RESULTS In vivo erectile responses to CNS were significantly decreased in all bilateral CNI groups compared to sham (p<0.05). Overall STIM 1 and 2 MPG protein expression increased however there were no significant differences in Orai isoforms. Gene expression in all SOC channels is increased 48 hours, 7 and 14 days following CNI with significant 2-fold increases in STIM 1, 2 and Orai 1, 3 14 days after CNI (p<0.05). Gene expression of apoptotic markers caspase 1 and 3 were significantly increased 48 hours, 7 and 14 days following CNI and returned to sham levels by 30 days. CONCLUSIONS CNI significantly impaired neurogenic-mediated erectile responses and was associated with a time-dependent increase in MPG caspase 1 and 3 gene expression. Increases in these MPG apoptotic cell markers correlated with an upregulation in gene expression of neuronal SOC channels suggesting a possible molecular mechanism of cavernous nerve degeneration after CNI. Elucidating the role of SOC channels in nerve injury and repair/regeneration may provide important insight into the molecular mechanisms of post-radical prostatectomy erectile dysfunction. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e331 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Johanna L. Hannan Baltimore, MD More articles by this author Omer Kutlu Baltimore, MD More articles by this author Xiaopu Liu Baltimore, MD More articles by this author Arthur L. Burnett Baltimore, MD More articles by this author Petter Hedlund Lund, Sweden More articles by this author Trinity J. Bivalacqua Baltimore, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...