Expression of Neurotrophic Factors in Neonatal Rats After Peripheral Inflammation

Chien, Chih Cheng; Fu, Wen‐Mei; Huang, Hsing‐I; Lai, Yeur‐Hur; Tsai, Yun‐Fang; Guo, Shu-Lin; Wu, Tzong-Jeng; Ling, Qing-Dong

doi:10.1016/j.jpain.2006.07.004

Cited by 30 publications

(26 citation statements)

References 51 publications

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“…Although numerous studies have suggested a central or peripheral role for p75 NTR after axotomy (Wakabayashi et al, 1998;Keast and Kepper, 2001;Hannila and Kawaja, 2005;Scott et al, 2005;Obata et al, 2006) or peripheral somatic inflammation (Cho et al, 1996;Pezet et al, 2001;Chien et al, 2007), few studies have examined the role of p75 NTR in normal or inflamed lower urinary tract pathways (Wakabayashi et al, 1996(Wakabayashi et al, , 1998(Wakabayashi et al, , 2002Vaidy- anathan Elsasser-Beile et al, 2000;Jahed and Kawaja, 2005;Tong and Cheng, 2005). To our knowledge, no studies have examined changes in p75 NTR expression in central or peripheral micturition reflex pathways after bladder inflammation.…”

Section: Discussionmentioning

confidence: 99%

p75^NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide‐induced cystitis

Klinger

Girard

Vizzard

2008

J of Comparative Neurology

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A role for nerve growth factor (NGF) in contributing to increased voiding frequency and altered sensation from the urinary bladder has been suggested. Previous studies have examined the expression and regulation of tyrosine kinase receptors (Trks) in micturition reflexes with urinary bladder inflammation. The present studies examine the expression and regulation of another receptor known to bind NGF, p75 NTR , after various durations of bladder inflammation induced by cyclophosphamide (CYP). CYP-induced cystitis increased (P Յ 0.001) p75NTR expression in the superficial lateral and medial dorsal horn in L1-L2 and L6 -S1 spinal segments. The number of p75 NTR -immunoreactive (-IR) cells in the lumbosacral dorsal root ganglia (DRG) also increased (P Յ 0.05) with CYP-induced cystitis (acute, intermediate, and chronic). Quantitative, real-time polymerase chain reaction also demonstrated significant increases (P Յ 0.01) in p75 NTR mRNA in DRG with intermediate and chronic CYP-induced cystitis. Retrograde dye-tracing techniques with Fastblue were used to identify presumptive bladder afferent cells in the lumbosacral DRG. In bladder afferent cells in DRG, p75 NTR -IR was also increased (P Յ 0.01) with cystitis. In addition to increases in p75 NTR -IR in DRG cell bodies, increases (P Յ 0.001) in pericellular (encircling DRG cells) p75 NTR -IR in DRG also increased. Confocal analyses demonstrated that pericellular p75 NTR -IR was not colocalized with the glial marker, glial fibrillary acidic protein (GFAP). These studies demonstrate that p75 NTR expression in micturition reflexes is present constitutively and modified by bladder inflammation. The functional significance of p75 NTR expression in micturition reflexes remains to be determined.

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Section: Discussionmentioning

confidence: 99%

p75^NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide‐induced cystitis

Klinger

Girard

Vizzard

2008

J of Comparative Neurology

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“…In addition to the role of NGF in bladder function, it has also been identified as a key molecule in the signaling of pain during inflammation (1,17,23,24,26,61). Visceral inflammation is often accompanied by an increase in sensitivity of somatic structures to noxious stimuli, commonly called referred hyperalgesia (9,75).…”

Section: Increased Somatic Sensitivity After Rvsmentioning

confidence: 99%

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

Merrill

Malley

Vizzard

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Merrill L, Malley S, Vizzard MA. Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression. Am J Physiol Regul Integr Comp Physiol 305: R147-R156, 2013. First published May 8, 2013 doi:10.1152/ajpregu.00089.2013.-Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P Յ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P Յ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P Յ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P Յ 0.01) increased at all monofilament forces tested (0.1-4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P Յ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity. micturition; stress; nerve growth factor; ELISA; somatic sensitivity STRESS CONTRIBUTES to symptom exacerbation in many disease states, including functional disorders of the urinary bladder such as overactive bladder (OAB) and interstitial cystitis (IC)/ bladder pain syndrome (BPS) (3,38,58,72). Urinary frequency is a common symptom among patients with OAB or IC/BPS, although the end result of frequent voiding may differ [reduce incontinence episodes (OAB) vs. reduce pain with bladder filling (IC/BPS)]. Patients with IC/BPS report symptom worsening during stress, as do patients with other disorders associated with IC/BPS including rheumatoid arthritis, psoriasis, and irritable bowel syndrome (47,72). Symptom worsening during stress may be due, in part, to disruption of the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol, through feedback on the HPA axis, normally acts to attenuate inflammation (47); however, abnormalities in the feedback may cause dysregulation of the inflammatory response. Therefore, patients...

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“…For example, both are involved in the regulation of inflammation as well as response to brain injury (18,24,(42)(43)(44)(45). Therefore, it is possible that p38 MAPK achieves these roles, in part, by increasing expression of p75 NTR .…”

Section: Because Induction Of P75mentioning

confidence: 99%

The p38 MAPK Pathway Mediates Aryl Propionic Acid–Induced Messenger RNA Stability of p75NTR in Prostate Cancer Cells

Quann¹,

Khwaja²,

Djakiew

2007

Cancer Research

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The p75 NTR acts as a tumor suppressor in the prostate, but its expression is lost as prostate cancer progresses and is minimal in established prostate cancer cell lines such as PC-3, DU-145, and LNCaP. Previously, we showed that treatment with R-flurbiprofen or ibuprofen induced p75 NTR expression in PC-3 and DU-145 cells leading to p75 NTR -mediated decreased survival. Here, we investigate the mechanism by which these drugs induce p75 NTR expression. We show that the observed increase in p75NTR protein due to R-flurbiprofen and ibuprofen treatment was accompanied by an increase in p75 NTR mRNA, and this increase in mRNA was the result of increased mRNA stability and not by an up-regulation of transcription. In addition, we show that treatment with R-flurbiprofen or ibuprofen led to sustained activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Furthermore, inhibition of the p38 MAPK pathway with the p38 MAPK-specific inhibitor SB202190 or by small interfering RNA (siRNA) knockdown of p38 MAPK protein prevented induction of p75 NTR by R-flurbiprofen and ibuprofen. We also observed that siRNA knockdown of MAPK-activated protein kinase (MK)-2 and MK3, the kinases downstream of p38 MAPK that are responsible for the mRNA stabilizing effects of the p38 MAPK pathway, also prevented an induction of p75 NTR by R-flurbiprofen and ibuprofen. Finally, we identify the RNA stabilizing protein HuR and the posttranscriptional regulator eukaryotic translation initiation factor 4E as two possible mechanisms by which the p38 MAPK pathway may increase p75 NTR expression. Collectively, the data suggest that R-flurbiprofen and ibuprofen induce p75 NTR expression by increased mRNA stability that is mediated through the p38 MAPK pathway. [Cancer Res 2007;67(23):11402-10]

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Expression of Neurotrophic Factors in Neonatal Rats After Peripheral Inflammation

Cited by 30 publications

References 51 publications

p75^NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide‐induced cystitis

p75^NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide‐induced cystitis

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

The p38 MAPK Pathway Mediates Aryl Propionic Acid–Induced Messenger RNA Stability of p75NTR in Prostate Cancer Cells

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Expression of Neurotrophic Factors in Neonatal Rats After Peripheral Inflammation

Cited by 30 publications

References 51 publications

p75NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide‐induced cystitis

p75NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide‐induced cystitis

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

The p38 MAPK Pathway Mediates Aryl Propionic Acid–Induced Messenger RNA Stability of p75NTR in Prostate Cancer Cells

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p75^NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide‐induced cystitis

p75^NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide‐induced cystitis