Constitutive expression Of NGF And P75NTR affected by bladder distension and NGF antisense treatment

Abstract

Aims 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 (p75NTR). Method 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/p75NTR expression was localized in harvested tissue. Key findings 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 p75NTR 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 p75NTR seen in the vehicle and scrambled ODN groups was reduced following treatment with NGF antisense. Significance The constitutive expression of NGF and p75NTR 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.

Expression of Low Affinity Nerve Growth Factor Receptor p75 in Classic Bladder Exstrophy

“…First, because of the staining for NGFR p75 used in this study, the results have to be interpreted carefully when drawing any conclusions on NGF itself. However, other studies have indicated a correlation between the expression of NGF and its low-affinity receptor p75 ( 18 , 30 ).…”

“…NGF can activate two specific receptors: the tyrosine kinase receptor A (Trk-A) and the p75 neurotrophin receptor (NGFR p75). NGFR p75, which is present in many different types of bladder cells, is well-established in animal models and also used in clinical studies ( 16 – 18 ). Whether and to what extent peri- and postoperative pain might be caused by structural or functional changes in the exstrophic bladder wall is yet unknown.…”

Caffeine improves bladder function in diabetic rats via a neuroprotective effect

“…NGF is a member of the neurotrophic factor family and is found primarily in sympathetic, partial sensory nerves and distributed target organs. Previous studies have demonstrated that NGF is associated with the pathogenesis of bladder dysfunction caused by multiple etiologies (11)(12)(13). NGF expression levels in tissues have been significantly decreased in clinical animal models and the promotion of NGF expression may improve the function of the bladder to a certain extent (11)(12)(13).…”

“…Previous studies have demonstrated that NGF is associated with the pathogenesis of bladder dysfunction caused by multiple etiologies ( 11-13 ). NGF expression levels in tissues have been significantly decreased in clinical animal models and the promotion of NGF expression may improve the function of the bladder to a certain extent ( 11-13 ). Additionally, BDNF is another important neurotrophic factor.…”

As neurotrofinas e a dor visceral: o caso particular do fator de crescimento neuronal e do fator neurotr�fico derivado do c�rebro

“…Além destes trabalhos com administração exógena, os efeitos da sobre-expressão do NGF têm sido bastante explorados em estudos recorrendo a modelos animais que tentam replicar patologias do trato urinário observadas em humano [58][59][60] . Os modelos de disfunção urinária mais utilizados incluem os modelos de inflamação da bexiga, maioritariamente induzidos pela administração intraperitonial de irritantes químicos como a ciclofosfamida 36,45,[61][62][63][64][65] , ou pela administração intravesical de polissacarídeos 66 , acido acético ou hidroclorídrico 67,68 , acetona 69 e terebentina 70 , entre outros 71 . Outros modelos focam-se na obstrução da uretra (BOO, do inglês bladder outlet obstruction) 25,72,73 , ou na indução de lesões na medula espinhal, que provocam a longo prazo hiperatividade da bexiga [74][75][76] .…”