Null mutations for exon III and exon IV of the p75 neurotrophin receptor gene enhance sympathetic sprouting in response to elevated levels of nerve growth factor in transgenic mice

Dhanoa, Navnish K.; Krol, Karmen M.; Jahed, Ali; Crutcher, Keith A.; Kawaja, Michael D.

doi:10.1016/j.expneurol.2005.12.022

Cited by 20 publications

(16 citation statements)

References 60 publications

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“…Whereas it is known that p75 NTR expression can enhance TrkA-NGF binding in some systems (1,9), p75 NTR may also reduce NGF-TrkA signaling by sequestering NGF (19,31,46). In the latter instance, any decrease or perturbation in NGF/ p75 NTR binding may tip the homeostatic equilibrium, resulting in increased NGF bioavailability to enhance NGF/TrkA signaling.…”

Section: Discussionmentioning

confidence: 94%

Role of p75^NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

Klinger

Vizzard²

2008

American Journal of Physiology-Renal Physiology

106

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NTR in bladder function in control and CYP-treated rats was determined using conscious cystometry and immunoneutralization or PD90780, a compound known to specifically block NGF binding to p75NTR . An anti-p75 NTR monoclonal antibody or PD90780 was infused intravesically and cystometric parameters were evaluated. Both methods of p75 NTR blockade significantly (P Յ 0.05) decreased the intercontraction interval and void volume in control and CYP-treated rats. Intravesical infusion of PD90780 also significantly (P Յ 0.001) increased intravesical pressure and increased the number of nonvoiding contractions during the filling phase. Control intravesical infusions of isotype-matched IgG and vehicle were without effect. Intravesical instillation of PD90780 significantly (P Յ 0.01) reduced the volume threshold to elicit a micturition contraction in control rats (no inflammation) and CYP-treated in a closed urinary bladder system. These studies demonstrate 1) ubiquitous p75 NTR expression in urinary bladder and increased expression with CYP-induced cystitis and 2) p75 NTR blockade at the level of the urinary bladder produces bladder hyperreflexia in control and CYP-treated rats. The overall activity of the urinary bladder reflects the balance of NGF-p75 NTR and NGF-TrkA signaling. NTR belongs to the tumor necrosis factor-␣ family of receptors (1, 4, 8). p75 NTR binds all neurotrophins, including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4/5. NGF-TrkA signaling is involved in some inflammatory effects of NGF (50), including sensitization of nociceptive afferents and the release of neuropeptides. TrkA expression is increased in bladder afferent cells in lumbosacral dorsal root ganglia (DRG) with acute and chronic cyclophosphamide (CYP)-induced bladder inflammation (51). In addition, p75 NTR expression is also significantly upregulated in bladder afferent cells (2.4-to 2.8-fold) in lumbosacral DRG after CYP-induced cystitis (39).The pan-neurotrophin receptor p75 NTR exhibits a ubiquitous distribution and has many functions and multiple binding partners and ligands (4,8). In the absence of Trk expression, p75NTR is suggested to be involved in apoptosis and regulation of neuronal growth (4, 27); however, in the presence of TrkA, p75 NTR is suggested to function by enhancing Trk binding to neurotrophins (3,4,70). p75 NTR expression has previously been identified in the urinary bladder (61,66,67) but few studies have examined the role of p75 NTR in bladder function or in the context of urinary bladder inflammation (66). Although we do know that p75NTR expression is present in micturition reflex pathways in control rats and is regulated with CYP-induced cystitis (39), the potential role(s) of p75 NTR in urinary bladder reflexes have not been explored. In this study, we determined 1) expression of p75 NTR in the urinary bladder with immunohistochemistry and Western blot and regulation of p75 NTR expression after CYP-induced cystitis, 2) the effect of immunoneutralization with an anti-p75 NTR monoc...

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Section: Discussionmentioning

confidence: 94%

Role of p75^NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

Klinger

Vizzard²

2008

American Journal of Physiology-Renal Physiology

106

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“…1B). This faint, residual staining may be attributed to the presence of readthrough transcripts (Lee et al, 1992) as well as the minor expression of a truncated protein product (Dhanoa et al, 2006) …”

Section: Antibody Characterizationmentioning

confidence: 94%

“…The p75 Ϫ/Ϫ mice were generated by placing a Neo-polyA cassette into the Bk site in exon 3, resulting in termination of most of the mRNAs at that point (Lee et al, 1992). Although there was some evidence for readthrough transcripts (Lee et al, 1992), as well as minor expression of a truncated protein product (Dhanoa et al, 2006), p75 Ϫ/Ϫ mice do not bind radio-iodinated NGF or have functional NGF receptors (Lee et al, 1992).…”

Section: P75mentioning

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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“…This antibody, developed in rabbit, was raised against a synthetic peptide (K-QRADIVESLCSESTATSPV) corresponding to the C-terminal of the rat p757NTR (amino acids 407-425 with N-terminally added lysine) conjugated to KLH. We have previously shown that while this antibody stains other smaller bands in addition to the 75 kDa form of this molecule on Western blot, specific immunostaining with this antibody was absent in sympathetic ganglia of mice lacking either exonIII or exonIV of this receptor (see Dhanoa et al, 2006).…”

Section: Immunofluorescencementioning

confidence: 95%

Olfactory ensheathing cells express smooth muscle α‐actin in vitro and in vivo

Jahed

Rowland

McDonald

et al. 2007

J of Comparative Neurology

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One strategy for spinal cord repair after injury that has moved quickly from the research laboratory to the clinic is the implantation of olfactory ensheathing cells (OECs). These unique glial cells of the olfactory system have been associated with axonal remyelination and regeneration after grafting into spinalized animals. Despite these promising observations, there remains a lack of direct empirical evidence of the exact fate of OECs after intraspinal implantation, in large part because of a surprising paucity of defined biomarkers that unequivocally distinguish these cells from phenotypically similar Schwann cells. Here we provide direct neurochemical proof that OECs, both in vitro and in vivo, express smooth muscle alpha-actin. That OECs synthesize this contractile protein (and a variety of actin-binding proteins including caldesmon) provides compelling evidence that these cells are, in fact, quite different from Schwann cells. The identification of several smooth muscle-related proteins in OECs points to a new appreciation of the structural and functional features of this population of olfactory glia. These biomarkers can now be used to elucidate the fate of OECs after intraspinal implantation, in particular assessing whether smooth muscle alpha-actin-expressing OECs are capable of facilitating axon remyelination and regeneration.

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Null mutations for exon III and exon IV of the p75 neurotrophin receptor gene enhance sympathetic sprouting in response to elevated levels of nerve growth factor in transgenic mice

Cited by 20 publications

References 60 publications

Role of p75^NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

Role of p75^NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

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

Olfactory ensheathing cells express smooth muscle α‐actin in vitro and in vivo

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Null mutations for exon III and exon IV of the p75 neurotrophin receptor gene enhance sympathetic sprouting in response to elevated levels of nerve growth factor in transgenic mice

Cited by 20 publications

References 60 publications

Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

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

Olfactory ensheathing cells express smooth muscle α‐actin in vitro and in vivo

Contact Info

Product

Resources

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Role of p75^NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

Role of p75^NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

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