MP56-07 EXPRESSION PROFILING OF EXPERIMENTAL NEUROGENIC BLADDER REVEALS DECREASED β3-ADRENERGIC RECEPTOR EXPRESSION THAT CAN BE REVERSED BY INOSINE TREATMENT
Year: 2018
Type: article
Abstract: You have accessJournal of UrologyPediatrics: Dysfunctional Voiding & Enuresis1 Apr 2018MP56-07 EXPRESSION PROFILING OF EXPERIMENTAL NEUROGENIC BLADDER REVEALS DECREASED β3-ADRENERGIC RECEPTOR EXPRESSION THAT CAN BE REVERSED BY INOSINE TREATMENT Bryan Sack, Mary Piper, Justin Cotellessa, Claire Doyle, Mehrnaz Gharaee-Kermani, Amy Avery, Fabliha Mahmood, Vivian Cristofaro, Maryrose Sullivan, Jill Macoska, and Rosalyn Adam Bryan SackBryan Sack More articles by this author , Mary PiperMary Piper More articles by this author , Justin CotellessaJustin Cotellessa More articles by this author , Claire DoyleClaire Doyle More articles by this author , Mehrnaz Gharaee-KermaniMehrnaz Gharaee-Kermani More articles by this author , Amy AveryAmy Avery More articles by this author , Fabliha MahmoodFabliha Mahmood More articles by this author , Vivian CristofaroVivian Cristofaro More articles by this author , Maryrose SullivanMaryrose Sullivan More articles by this author , Jill MacoskaJill Macoska More articles by this author , and Rosalyn AdamRosalyn Adam More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1798AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Neurogenic detrusor overactivity (NDO) is a devastating consequence of suprasacral spinal cord injury (SCI). Prior studies in our group revealed significant improvement in NDO in rats receiving chronic, systemic administration of the purine nucleoside inosine. However the molecular pathways underlying improvement are incompletely defined. The objective of this study was to use unbiased expression profiling to assess time-dependent transcriptional changes following SCI and to determine how expression of specific genes was altered by inosine. METHODS RNAseq analysis was performed on full thickness bladder tissue from rats 2, 8 or 16 weeks after mid-thoracic spinal cord transection or from age-matched, non-injured controls. Differential gene expression and gene pattern clustering were performed using DESeq2 and DEGreport, respectively. In a separate cohort of animals, inosine was administered daily for 6 weeks by intraperitoneal injection. In each case, validation of gene expression changes was performed using real time RT-PCR. RESULTS 207, 1355, and 2493 differentially expressed genes (DEGs) were identified at the 2, 8, and 16 week timepoints, respectively, with significant enrichment for gene ontology terms associated with cytoskeletal remodeling, synapse organization, axon guidance and neuromuscular junction activity. Among the significant DEGs, the beta 3-adrenergic receptor (β3-AR) was downregulated following SCI, whereas the M3 muscarinic receptor remained unchanged, suggesting a potential imbalance between sympathetic and parasympathetic responses. Notably, inosine treatment increased β3-AR levels in bladder tissue from SCI rats ˜5-fold compared to vehicle-treated controls, and also increased β3-AR protein levels. In contrast, M3 mRNA levels were unaffected by inosine treatment. CONCLUSIONS Expression profiling of bladder tissue following SCI reveals perturbations in a variety of physiologically relevant gene clusters including those associated with innervation and cytoskeletal remodeling. Decreased β3-AR levels may reduce responses to sympathetic activity in the bladder leading to the development of NDO following SCI, whereas β3-AR levels can be reversed by treatment with inosine. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e758-e759 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Bryan Sack More articles by this author Mary Piper More articles by this author Justin Cotellessa More articles by this author Claire Doyle More articles by this author Mehrnaz Gharaee-Kermani More articles by this author Amy Avery More articles by this author Fabliha Mahmood More articles by this author Vivian Cristofaro More articles by this author Maryrose Sullivan More articles by this author Jill Macoska More articles by this author Rosalyn Adam More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Language: English
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2795722132