Increased levels of nerve growth factor in the urinary bladder and hypertrophy of dorsal root ganglion neurons in the diabetic rat

Steinbacher, B. C.; Nadelhaft, Irving

doi:10.1016/s0006-8993(97)01287-0

Cited by 49 publications

(29 citation statements)

References 20 publications

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“…Previous studies have also revealed that diabetic rats exhibited decreased NGF pro- duction in target organs, as well as reduced axonal transport of NGF in afferent pathways (5,26). We have also recently found that the time-dependent reduction in tissue NGF levels in the bladder and lumbosacral DRGs, which contain bladder afferent neurons, is well correlated with bladder dysfunction in diabetic rats up to 12 weeks after STZ injection (4), although early increases in NGF levels in the diabetic rat bladder have also been reported (27). In addition, it has also been shown that change in the levels of other neurotrophic factors, such as tissue neurotro-…”

Section: Discussionmentioning

confidence: 93%

Gene Therapy Using Replication-Defective Herpes Simplex Virus Vectors Expressing Nerve Growth Factor in a Rat Model of Diabetic Cystopathy

et al. 2004

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Diabetic cystopathy is one of the common complications of diabetes and current therapy is limited. In the present study, the effects of gene therapy, using replication-defective herpes simplex virus type 1 (HSV-1) vectors to deliver and express the nerve growth factor (NGF) gene (HSV-NGF) on tissue NGF levels and bladder function, were evaluated in streptozotocin (STZ)-induced diabetic rats. Diabetic rats exhibited a significant decrease in NGF levels in the bladder and lumbosacral dorsal root ganglia (DRG) detected by enzyme-linked immunosorbent assay and displayed marked bladder dysfunction 12 weeks after STZ injection. In contrast, rats with bladder wall injection of the NGF expression vector 8 weeks after STZ treatment exhibited a significant increase of NGF levels in the bladder and L6 DRG 4 weeks after HSV-NGF injection. Along with the restoration of tissue NGF expression, in metabolic cage studies and cystometry, HSV-NGF-injected rats also showed significantly reduced bladder capacity and postvoid residual volume than diabetic rats injected with the control vector (HSV-lacZ), indicating that voiding function was improved after HSV vector-mediated NGF gene delivery. Thus, HSV vectormediated NGF gene therapy may prove useful to restore decreased NGF expression in the bladder and bladder afferent pathways, thereby improving hypoactive bladder function in diabetes. Diabetes 53

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Section: Discussionmentioning

confidence: 93%

Gene Therapy Using Replication-Defective Herpes Simplex Virus Vectors Expressing Nerve Growth Factor in a Rat Model of Diabetic Cystopathy

et al. 2004

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“…mTOR is a component of one of three major NGF signaling pathways, the well-established prosurvival pathway: PI3K/Akt/mTOR pathway (36); it both suppresses apoptosis and promotes cellular growth (17). Studies to date have focused on whole bladder expression of NGF in animal models of DM (45,67,74). A temporal decline (9 -12 wk post-STZ-DM induction in rat) in whole bladder NGF levels has been proposed to be a permissive/causative factor in DBD by affecting A␦-and c-fiber bladder afferent pathways (67).…”

Section: J-l)mentioning

confidence: 99%

Impact of diabetes mellitus on bladder uroepithelial cells

Hanna-Mitchell

Ruiz

Daneshgari

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes mellitus (DM), is characterized by a broad spectrum of symptoms including urinary urgency, frequency, and incontinence. As DBD is commonly diagnosed late, it is important to understand the chronic impact of DM on bladder tissues. While changes in bladder smooth muscle and innervation have been reported in diabetic patients, the impact of DM on the specialized epithelial lining of the urinary bladder, the urothelium (UT), is largely unknown. Quantitative polymerase chain reaction analysis and electron microscopy were used to evaluate UT gene expression and cell morphology 3, 9, and 20 wk following streptozotocin (STZ) induction of DM in female SpragueDawley rats compared with age-matched control tissue. Desquamation of superficial (umbrella) cells was noted at 9 wk DM, indicating a possible breach in barrier function. One causative factor may be metabolic burden due to chronic hyperglycemia, suggested by upregulation of the polyol pathway and glucose transport genes in DM UT. While superficial UT repopulation occurred by 20 wk DM, the phenotype was different, with significant upregulation of receptors associated with UT mechanosensation (transient receptor potential vanilloid subfamily member 1; TRPV1) and UT autocrine/paracrine signaling (acetylcholine receptors AChR-M2 and -M3, purinergic receptors P2X2 and P2X3). Compromised barrier function and alterations in UT mechanosensitivity and cell signaling could contribute to bladder instability, hyperactivity, and altered bladder sensation by modulating activity of afferent nerve endings, which appose the urothelium. Our results show that DM impacts urothelial homeostasis and may contribute to the underlying mechanisms of DBD. streptozotocin; urothelium; barrier; sensory; diabetic bladder dysfunction IN THE UNITED STATES alone it is estimated that approximately 19 million individuals, comprising both men and women, suffer from diabetes mellitus (DM) (13). DM is characterized by defects in the secretion of the hormone insulin by the pancreas and/or insulin signaling (53), which causes a dysregulation of cellular glucose uptake. Glucose is a large hydrophilic molecule that depends on specific glucose transporter (GLUT) proteins, present on the cell membrane, for cellular entry (12). From the GLUT family (13 cloned to date), GLUT4 is regulated by insulin and controls glucose uptake by skeletal muscle [which accounts for ϳ40% of total body mass (70)], cardiac muscle, and adipose tissue (75). Thus Type 1 and 2 diabetics are unable to efficiently transport glucose from the blood into these tissue groups (66) resulting in a state of hyperglycemia. Consequently, glucose inundates cells that express insulinindependent glucose transporters (such as GLUT1). Chronic elevation in cytosolic glucose leads to metabolic abnormalities such as osmotic and oxidative stress, thought to be factors that contribute to tissue injury and dysfunction associated with long-term DM (15, 61).The urinary bladder is one of th...

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“…Ischemic condition in the bladder involves partial denervation and a compensatory increase in nerve growth factor expression [4][5][6] . An increase in nerve growth factor leads to neuronal hypertrophy and bladder nerve sensitization [7,8] . Although ischemia induces denervation as a morphological change, sensitization of nerves in the bladder is evoked phenotypically.…”

Section: Introductionmentioning

confidence: 99%

Silodosin, an α<sub>1A</sub>-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow

Goi

Tomiyama²,

Maruyama³

et al. 2016

Pharmacology

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Background/Aims: This study was performed to investigate the detailed mechanism underlying the effects of the selective α_1A-adrenoceptor antagonist, silodosin, on bladder function in a rat model of atherosclerosis-induced chronic bladder ischemia (CBI). Methods: The CBI model was prepared by balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, the CBI rats received either silodosin or vehicle alone subcutaneously for 8 weeks. Rats received a 2% cholesterol diet throughout the experiment. Bladder blood flow (BBF) was measured. Immunohistochemical staining was performed to determine the nerve distribution and nerve growth factor expression in the bladder. Bladders were used for muscle strip contraction analysis. The expression levels of muscarinic M2 and M3 receptors were measured. Results: Silodosin abrogated the decrease in BBF in CBI rats. Silodosin prevented the decrease in nerve distribution and increase in nerve growth factor expression in the CBI model. Bladder contractile response was reduced in the CBI group. Silodosin ameliorated the effect on the bladder contractile response. The level of muscarinic M3 receptor mRNA present in the bladder of CBI rats was increased by silodosin. Conclusion: The results of this study suggest that silodosin ameliorates the denervation of the bladder and effects on detrusor contractile function under ischemic conditions by restoring BBF.

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Increased levels of nerve growth factor in the urinary bladder and hypertrophy of dorsal root ganglion neurons in the diabetic rat

Cited by 49 publications

References 20 publications

Gene Therapy Using Replication-Defective Herpes Simplex Virus Vectors Expressing Nerve Growth Factor in a Rat Model of Diabetic Cystopathy

Gene Therapy Using Replication-Defective Herpes Simplex Virus Vectors Expressing Nerve Growth Factor in a Rat Model of Diabetic Cystopathy

Impact of diabetes mellitus on bladder uroepithelial cells

Silodosin, an α<sub>1A</sub>-Adrenoceptor Antagonist, May Ameliorate Ischemia-Induced Bladder Denervation and Detrusor Dysfunction by Improving Bladder Blood Flow

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