scholarly journals Balanced levels of nerve growth factor are required for normal pregnancy progression

Reproduction ◽  
2014 ◽  
Vol 148 (2) ◽  
pp. 179-189 ◽  
Author(s):  
Pierre Frank ◽  
Gabriela Barrientos ◽  
Irene Tirado-González ◽  
Marie Cohen ◽  
Petra Moschansky ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Ovarian Function ◽  
Critical Role ◽  
Fetal Loss ◽  
Placental Tissue ◽  
Normal Pregnancy ◽  
Placental Development ◽  
Local Inflammatory Response ◽  
Nerve Growth

Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P+ nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation.

scholarly journals Critical Role for Kalirin in Nerve Growth Factor Signaling through TrkA

2005 ◽  
Vol 25 (12) ◽  
pp. 5106-5118 ◽  
Author(s):  
Kausik Chakrabarti ◽  
Rong Lin ◽  
Noraisha I. Schiller ◽  
Yanping Wang ◽  
David Koubi ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Critical Role ◽  
Neuronal Morphology ◽  
Neurotrophin Receptor ◽  
General Mechanism ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Nerve Growth

ABSTRACT Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low concentration of NGF. Furthermore, elevated Kalirin expression resulted in catalytic activation of TrkA, as demonstrated by in vitro kinase assays and increased NGF-stimulated cellular activation of Rac, Mek, and CREB. Domain mapping demonstrated that the N-terminal Kalirin pleckstrin homology domain mediates the interaction with TrkA. The effects of Kalirin on TrkA provide a molecular basis for the requirement of Kalirin in process extension from PC12 cells and for previously observed effects on axonal extension and dendritic maintenance. The interaction of TrkA with the pleckstrin homology domain of Kalirin may be one example of a general mechanism whereby receptor/Rho GEF pairings play an important role in receptor tyrosine kinase activation and signal transduction.

scholarly journals The Copper(II)-Assisted Connection between NGF and BDNF by Means of Nerve Growth Factor-Mimicking Short Peptides

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 301 ◽  
Author(s):  
Irina Naletova ◽  
Cristina Satriano ◽  
Adriana Pietropaolo ◽  
Fiorenza Gianì ◽  
Giuseppe Pandini ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Noncovalent Interactions ◽  
Critical Role ◽  
Camp Response Element Binding ◽  
Copper Binding ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Nerve Growth

Nerve growth factor (NGF) is a protein necessary for development and maintenance of the sympathetic and sensory nervous systems. We have previously shown that the NGF N-terminus peptide NGF(1-14) is sufficient to activate TrkA signaling pathways essential for neuronal survival and to induce an increase in brain-derived neurotrophic factor (BDNF) expression. Cu2+ ions played a critical role in the modulation of the biological activity of NGF(1-14). Using computational, spectroscopic, and biochemical techniques, here we report on the ability of a newly synthesized peptide named d-NGF(1-15), which is the dimeric form of NGF(1-14), to interact with TrkA. We found that d-NGF(1-15) interacts with the TrkA-D5 domain and induces the activation of its signaling pathways. Copper binding to d-NGF(1-15) stabilizes the secondary structure of the peptides, suggesting a strengthening of the noncovalent interactions that allow for the molecular recognition of D5 domain of TrkA and the activation of the signaling pathways. Intriguingly, the signaling cascade induced by the NGF peptides ultimately involves cAMP response element-binding protein (CREB) activation and an increase in BDNF protein level, in keeping with our previous result showing an increase of BDNF mRNA. All these promising connections can pave the way for developing interesting novel drugs for neurodegenerative diseases.

Participation of nerve growth factor in the regulation of ovarian function

Zygote ◽  
1996 ◽  
Vol 4 (04) ◽  
pp. 309-312 ◽  
Author(s):  
Gregory A Dissen ◽  
Artur Mayerhofer ◽  
Sergio R. Ojeda
Keyword(s):  
Nervous System ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Ovarian Function ◽  
Nerve Growth ◽  
Related Target ◽  
Neuronal Populations ◽  
Survival And Development ◽  
New Evidence ◽  
Biological Actions

Nerve growth factor (NGF) belongs to a family of related target-derived proteins required for the survival and development of discrete neuronal populations in the central and peripheral nervous systems (Levi-Montalcini, 1987; Snider, 1994). Although initial observations led to the conclusion that the biological actions of neurotrophins are restricted to the nervous system (Thoenen, 1991; Raffioniet al.1993), new evidence suggests that they, and in particular NGF, can also affect non-neuronal cells.

scholarly journals Imbalance of the Nerve Growth Factor and Its Precursor as a Potential Biomarker for Diabetic Retinopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
B. A. Mysona ◽  
S. Matragoon ◽  
M. Stephens ◽  
I. N. Mohamed ◽  
A. Farooq ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Experimental Diabetes ◽  
Critical Role ◽  
Diabetic Patients ◽  
Retinal Damage ◽  
Nerve Growth ◽  
Potential Biomarker ◽  
Early Biomarker

Our previous studies have demonstrated that diabetes-induced oxidative stress alters homeostasis of retinal nerve growth factor (NGF) resulting in accumulation of its precursor, proNGF, at the expense of NGF which plays a critical role in preserving neuronal and retinal function. This imbalance coincided with retinal damage in experimental diabetes. Here we test the hypothesis that alteration of proNGF and NGF levels observed in retina and vitreous will be mirrored in serum of diabetic patients. Blood and vitreous samples were collected from patients (diabetic and nondiabetic) undergoing vitrectomy at Georgia Regents University under approved IRB. Levels of proNGF, NGF, andp75NTRshedding were detected using Western blot analysis. MMP-7 activity was also assayed. Diabetes-induced proNGF expression and impaired NGF expression were observed in vitreous and serum. Vitreous and sera from diabetic patients(n=11)showed significant 40.8-fold and 3.6-fold increases, respectively, compared to nondiabetics(n=9). In contrast, vitreous and sera from diabetic patients showed significant 44% and 64% reductions in NGF levels, respectively, compared to nondiabetics. ProNGF to NGF ratios showed significant correlation between vitreous and serum. Further characterization of diabetes-induced imbalance in the proNGF to NGF ratio will facilitate its utility as an early biomarker for diabetic complications.

scholarly journals CUMS Promotes the Development of Premature Ovarian Insufficiency Mediated by Nerve Growth Factor and Its Receptor in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xiaoyan Fu ◽  
Qun Zheng ◽  
Ning Zhang ◽  
Mingxing Ding ◽  
Xiaoming Pan ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Premature Ovarian Insufficiency ◽  
Mild Stress ◽  
Ovarian Insufficiency ◽  
Female Population ◽  
Nerve Growth

This study aimed to investigate whether chronic unpredictable mild stress (CUMS) affects follicular development in ovaries through the nerve growth factor (NGF)/high affinity nerve growth factor receptor, the Tropomyosin-related kinase A (TrkA) receptor, mediated signaling pathway and to reveal the relationship between chronic stress and premature ovarian insufficiency (POI) development. In this experiment, a CUMS rat model was constructed. It was found that serum estradiol (E2), anti-Mullerian hormone (AMH), and gonadotropin-releasing hormone (GnRH) levels decreased, while follicle-stimulating hormone (FSH) levels increased. The expression of NGF, TrkA, p75, and FSHR in ovarian tissue decreased significantly. The expression levels of TrkA and p75 protein in ovarian stroma and small follicles were observed by an immunofluorescence assay. In addition, the numbers of small follicles were significantly reduced. The expression of TrkA, p75, and FSHR in CUMS ovarian tissue was upregulated by exogenous NGF in vitro. Furthermore, after treatment with NGF combined with FSH, E2 secretion in ovarian tissue culture supernatant of CUMS rats also increased significantly. Therefore, CUMS downregulates NGF and TrkA and promotes the occurrence of POI in rats. Exogenous NGF and FSH can upregulate the NGF receptor, E2, and AMH in vitro, and improve the rat ovarian function. Future studies may associate these results with female population.

Isolation of human nerve growth factor from placental tissue

1978 ◽  
Vol 3 (2) ◽  
pp. 175-183 ◽  
Author(s):  
L. D. Goldstein ◽  
C. P. Reynolds ◽  
J. R. Perez-Polo
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Placental Tissue ◽  
Nerve Growth ◽  
Human Nerve

scholarly journals Influence of Previous COVID-19 and Mastitis Infections on the Secretion of Brain-Derived Neurotrophic Factor and Nerve Growth Factor in Human Milk

2021 ◽  
Vol 22 (8) ◽  
pp. 3846
Author(s):  
Veronique Demers-Mathieu ◽  
Dustin J. Hines ◽  
Rochelle M. Hines ◽  
Sirima Lavangnananda ◽  
Shawn Fels ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Breast Milk ◽  
Human Milk ◽  
Neurotrophic Factor ◽  
Critical Role ◽  
Brain Derived Neurotrophic Factor ◽  
Nerve Growth ◽  
Milk Samples ◽  
The Impact

Background: Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) play a critical role in neurodevelopment, where breast milk is a significant dietary source. The impact of previous COVID-19 infection and mastitis on the concentration of BDNF and NGF in human milk was investigated. Methods: Concentrations of BDNF and NGF were measured via ELISA in human milk samples collected from 12 mothers with a confirmed COVID-19 PCR, 13 mothers with viral symptoms suggestive of COVID-19, and 22 unexposed mothers (pre-pandemic Ctl-2018). These neurotrophins were also determined in 12 mothers with previous mastitis and 18 mothers without mastitis. Results: The NGF concentration in human milk was lower in the COVID-19 PCR and viral symptoms groups than in the unexposed group, but BDNF did not differ significantly. Within the COVID-19 group, BDNF was higher in mothers who reported headaches or loss of smell/taste when compared with mothers without the respective symptom. BDNF was lower in mothers with mastitis than in mothers without mastitis. Conclusions: Previous COVID-19 and mastitis infections changed differently the secretion of NGF and BDNF in human milk. Whether the changes in NGF and BDNF levels in milk from mothers with infection influence their infant’s development remains to be investigated.

scholarly journals E2F4 Actively Promotes the Initiation and Maintenance of Nerve Growth Factor-Induced Cell Differentiation

1999 ◽  
Vol 19 (9) ◽  
pp. 6048-6056 ◽  
Author(s):  
Stephan P. Persengiev ◽  
Ivanela I. Kondova ◽  
Daniel L. Kilpatrick
Keyword(s):  
Cell Differentiation ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Growth Regulation ◽  
Critical Role ◽  
Terminal Differentiation ◽  
Nerve Growth

ABSTRACT E2F transcription factors play a critical role in cell cycle progression through the regulation of genes required for G1/S transition. They are also thought to be important for growth arrest; however, their potential role in the cell differentiation process has not been previously examined. Here, we demonstrate that E2F4 is highly upregulated following the neuronal differentiation of PC12 cells with nerve growth factor (NGF), while E2F1, E2F3, and E2F5 are downregulated. Immunoprecipitation and subcellular fractionation studies demonstrated that both the nuclear localization of E2F4 and its association with the Rb family member p130 increased following neuronal differentiation. The forced expression of E2F4 markedly enhanced the rate of PC12 cell differentiation induced by NGF and also greatly lowered the rate at which cells lost their neuronal phenotype following NGF removal. Importantly, this effect occurred in the absence of any significant change in the growth regulation of PC12 cells by NGF. Further, the downregulation of E2F4 expression with antisense oligodeoxynucleotides inhibited NGF-induced neurite outgrowth, indicating an important role for this factor during PC12 cell differentiation. Finally, E2F4 expression was found to increase dramatically in the developing rat cerebral cortex and cerebellum, as neuroblasts became postmitotic and initiated terminal differentiation. These findings demonstrate that, in addition to its effects on cell proliferation, E2F4 actively promotes the neuronal differentiation of PC12 cells as well as the retention of this state. Further, this effect is independent of alterations in cell growth and may involve interactions between E2F4 and the neuronal differentiation program itself. E2F4 may be an important participant in the terminal differentiation of neuroblasts.

scholarly journals Anti-nerve growth factor monoclonal antibodies for the control of pain in dogs and cats

2018 ◽  
Vol 184 (1) ◽  
pp. 23-23 ◽  
Author(s):  
Masataka Enomoto ◽  
Patrick W Mantyh ◽  
Joanna Murrell ◽  
John F Innes ◽  
B Duncan X Lascelles
Keyword(s):  
Chronic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Sympathetic Neurons ◽  
Critical Role ◽  
Current Status ◽  
Effective Control ◽  
Novel Therapy ◽  
Nerve Growth ◽  
Species Specific

Nerve growth factor (NGF) is essential for the survival of sensory and sympathetic neurons during development. However, in the adult, NGF and its interaction with tropomyosin receptor kinase A receptor (TrkA) has been found to play a critical role in nociception and nervous system plasticity in pain conditions. Thus, various monoclonal antibody (mAb) therapies targeting this pathway have been investigated in the development of new pharmacotherapies for chronic pain. Although none of the mAbs against NGF are yet approved for use in humans, they look very promising for the effective control of pain. Recently, species-specific anti-NGF mAbs for the management of osteoarthritis (OA)-associated pain in dogs and cats has been developed, and early clinical trials have been conducted. Anti-NGF therapy looks to be both very effective and very promising as a novel therapy against chronic pain in dogs and cats. This review outlines the mechanism of action of NGF, the role of NGF in osteoarthritis, research in rodent OA models and the current status of the development of anti-NGF mAbs in humans. Furthermore, we describe and discuss the recent development of species-specific anti-NGF mAbs for the treatment of OA-associated pain in veterinary medicine.

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