MP89-20 BDNF OVEREXPRESSION ALTERS THE PHENOTYPE OF CHOLINERGIC NEURONS IN RAT BLADDER

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Non-Neurogenic Voiding Dysfunction1 Apr 2015MP89-20 BDNF OVEREXPRESSION ALTERS THE PHENOTYPE OF CHOLINERGIC NEURONS IN RAT BLADDER Mahendra Kashyap, Subrata Pore, Willam C. Degroat, Christopher J. Chermansky, Naoki Yoshimura, and Pradeep Tyagi Mahendra KashyapMahendra Kashyap More articles by this author , Subrata PoreSubrata Pore More articles by this author , Willam C. DegroatWillam C. Degroat More articles by this author , Christopher J. ChermanskyChristopher J. Chermansky More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and Pradeep TyagiPradeep Tyagi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1819AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Evidence for Brain-derived neurotrophic factor (BDNF) overexpression in OAB is indicated by urine analysis of OAB patients and from animal studies involving detrusor overactivity induced by chemicals or by spinal cord injury. Studies in cardiac field indicate that BDNF signaling enhances parasympathetic tone, but the effect of BDNF overexpression on the phenotype of cholinergic neurons in bladder remain to be investigated. Since spinal cord injury and chemicals induces several other chemicals besides BDNF, we investigated its effect on cholinergic neurons in rat bladder transfected with exogenous BDNF plasmid. METHODS Under isoflurane anesthesia, the bladder wall of adult female Sprague-Dawley rats were non-virally transfected with either 10μg of plasmid DNA encoding the rat BDNF transgene or luciferase plasmid. A week later, bladder tissue was harvested to analyze the expression by immunoreactivity, qPCR and Western blot for BDNF and the proteins involved in neuroexocytosis of acetylcholine. RESULTS 10 fold higher expression of cholinergic neuron specific proteins such as choline acetyltransferase (ChAT) red stain merged with green immunoreactivity for BDNF expression in rat injected with BDNF transgene, compared to rat group injected with luciferase (LUCI). Lumen is indicated by arrow and blue DAPI stains the nucleus in image. Significant upregulation (P<0.05) in high-affinity and low affinity receptor for BDNF namely, TrkB and P75NTR by 4.2 fold and 3.6 fold, respectively was observed. There was 14 fold increase in expression of □1 receptors along with modest rise in Vesicular ACh transporter (VAChT) for facilitating ACh release. Expression of molecules involved in downstream signaling pathways namely, phospholipase C-γ (PLCγ2) and PLCγ1 was increased 51 and 5.5 fold, respectively. CONCLUSIONS Our findings reveal a previously unknown role for BDNF in enhancing the Ach release in bladder through altered phenotype of cholinergic neurons innervating bladder. BDNF induced alterations in the expressions of proteins involved in neuroexocytosis of ACh, especially ChAT, VAChT and α1 adrenergic receptors in bladder establish a mechanistic link between detrusor overactivity and BDNF overexpression induced by chemical or by genetic means. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1108 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mahendra Kashyap More articles by this author Subrata Pore More articles by this author Willam C. Degroat More articles by this author Christopher J. Chermansky More articles by this author Naoki Yoshimura More articles by this author Pradeep Tyagi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...