title: Constitutive expression Of NGF And P75(NTR) affected by bladder distension and NGF antisense treatment.
abstract: OBJECTIVE
  It is known that bladder exposure to noxious stimuli elicits nerve growth factor (NGF) expression with region wise differences. Here, we investigated the effect of bladder distension (cystometry) and bladder wall injection of NGF antisense oligonucleotide (ODN) together as well as separately on spontaneous (constitutive) expression of NGF and its cognate p75 neurotrophin receptor (p75(NTR)).
  
  
  METHODS
  Under isoflurane anesthesia, either 15μg of protamine sulfate (vehicle) alone or complexed with 1.5μg of NGF antisense or scrambled ODN was injected (10μL) at 4 sites in bladder wall of 24 adult female Sprague-Dawley rats and 6 rats were left untreated (n=30). Under urethane anesthesia, cystometry (CMG) was performed in treated and control rats. Fluorescent ODN and NGF/p75(NTR) expression was localized in harvested tissue.
  
  
  RESULTS
  Complexation of ODN with protamine was essential for the retention of ODN in bladder tissue as the uncomplexed ODN was untraceable after injection. Bladder distension from CMG raised the expression of NGF and p75(NTR) relative to CMG naïve rats. The groups treated with vehicle, scrambled and antisense ODN were indistinct with regard to CMG parameters, but the intense immunoreactivity of NGF and p75(NTR) seen in the vehicle and scrambled ODN groups was reduced following treatment with NGF antisense.
  
  
  CONCLUSIONS
  The constitutive expression of NGF and p75(NTR) is responsive to bladder distension and administration of NGF antisense. Complexation with protamine reduces the clearance of ODN and demonstrates the potential of ODN nanoparticles as an option for reducing the inducible NGF expression in OAB patients following intradetrusor injection.
authors: Department of Urology, University of Pittsburgh, Pittsburgh, United States.
authors: Mahendra
authors: M
authors: Kashyap
authors: Department of Urology, University of Pittsburgh, Pittsburgh, United States.
authors: Subrata
authors: S
authors: Pore
authors: Department of Urology, University of Pittsburgh, Pittsburgh, United States.
authors: Naoki
authors: N
authors: Yoshimura
authors: Department of Urology, University of Pittsburgh, Pittsburgh, United States. Electronic address: prt18@pitt.edu.
authors: Pradeep
authors: P
authors: Tyagi
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis*; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D001745:Urinary Bladder Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat; D020932:Nerve Growth Factor
keywords: Constitutive; NGF; Protamine; Reflex voiding; p75(NTR)