Role Of Nerve Growth Factor Research Articles

Clinicopathological Insights to the Nerve Growth Factor NGF Associated Stress Response in Pregnancy and Therapeutic Potential in Fetal Neurodevelopment

The nerve growth factor has a significant role in fetal neurogenesis and sustaining pregnancy. Objectives: To investigate the effects of nerve growth factor in stress response during pregnancy on developing fetus to bring clinicopathological correlation on the role of nerve growth factor in maternal stress markers (cortisol levels, glucocorticoids, depression, anxiety, and brain-derived neurotrophic factor levels) and fetal brain development. Methods: Following PRISMA guidelines, this study was extracted from PubMed, ScienceDirect, Nature, and Google Scholar articles from January 2014 to April 2024. The examination of pregnant women in published research gave a possibility to understand the application of nerve growth factor as a suitable biomarker for brain stress and fetal neuronal development. To exclude studies with lower ranks, each of the selected studies was assessed for adherence to evidence-based research methodology. The studies were taken from China, Europe, America and South Asia (including Pakistan). Results: Increased nerve growth factor levels were associated with maternal stress reactions which caused changes in cortisol levels and the amygdaloidal complex area. However, the increased nerve growth factor level was linked to changes in the fetal brain such as the weight of the fetal brain and stress biomarkers in the amniotic fluid sample inferring a critical role in the modulation of maternal stress on the fetal neurodevelopmental spheres. Conclusions: It was concluded that it is important to note how stress and nerve growth factors interact during pregnancy to create effective interventions to reduce stress dependence for the better health of both the mother and child.

Effect of New Antidiabetics on Steatosis in Nerve Tissues and Nerve Conduction Velocity: Possible Role of Nerve Growth Factor (NGF)/Synaptophysin and Nrf2/HO-1 Pathways.

The current study aims to investigate the impact of the GLP1 analog (semaglutide) and SGLT2 inhibitor (dapagliflozin) on nerve functions, morphology, and the underlying mechanisms involving nerve growth factor (NGF)/synaptophysin and Nrf2/HO-1 pathways in obese rats. Forty male Sprague Dawley rats, aged six to eight weeks, were classified into five groups; normal group (high-fat diet {HFD} for 12 weeks, metformin group (HFD for 12 weeks + metformin in last four weeks), dapagliflozin group (HFD for 12 weeks +dapagliflozin in last four weeks, semaglutide group (HFD for 12 weeks + semaglutide in last four weeks). At the end of the experiment, the sciatic nerve was collected for nerve conduction study, oxidative stress marker (malondialdehyde, i.e., MDA), real-time polymerase chain reaction (PCR) study (for HO-1 and Nrf2), oil red O staining, electron microscopic examination and immunohistochemistry for NGF and synaptophysin. The HFD group showed a significant rise in blood glucose, serum lipids, homeostatic model assessment (HOMA) index, lipid deposition in nerve tissues, and lipid peroxidation (MDA) in nerve tissues with significant attenuation in nerve conduction velocity (NCV), the expression of Nrf2 and HO-1 genes and significant attenuation in area stained with NGF and synaptophysin. On the other hand, pretreatment with either dapagliflozin or semaglutide led to considerable enhancement in the deteriorated serum and nerve tissue parameters and reversed the pathological changes. New antidiabetic drugs like SGLT2 inhibitors (more powerful) and GLP1 analog might have neuroprotective beneficial effects besides controlling the glycemic state in obese rats. This effect may result from reduced oxidative stress and increased Nrf2 levels, HO-1, synaptophysin, and NGF in the nerve tissues of obese rats.

Multifaceted Roles of Nerve Growth Factor: A Comprehensive Review with a Special Insight into Pediatric Perspectives.

Nerve growth factor (NGF) is a neurotrophic peptide largely revealed for its ability to regulate the growth and survival of peripheral sensory, sympathetic, and central cholinergic neurons. The pro-survival and regenerative properties of neurotrophic factors propose a therapeutic potential in a wide range of brain diseases, and NGF, in particular, has appeared as an encouraging potential treatment. In this review, a summary of clinical studies regarding NGF and its therapeutic effects published to date, with a specific interest in the pediatric context, will be attempted. NGF has been studied in neurological disorders such as hypoxic-ischemic encephalopathy, traumatic brain injury, neurobehavioral and neurodevelopmental diseases, congenital malformations, cerebral infections, and in oncological and ocular diseases. The potential of NGF to support neuronal survival, repair, and plasticity in these contexts is highlighted. Emerging therapeutic strategies for NGF delivery, including intranasal administration as well as advanced nanotechnology-based methods, are discussed. These techniques aim to enhance NGF bioavailability and target specificity, optimizing therapeutic outcomes while minimizing systemic side effects. By synthesizing current research, this review underscores the promise and challenges of NGF-based therapies in pediatric neurology, advocating for continued innovation in delivery methods to fully harness NGF's therapeutic potential.

The role of nerve growth factor in traumatic brain injury

Nerve growth factor (NGF), a crucial member of neurotrophic factors (NTFs), plays a significant role in various diseases, including spinal cord injury, brain ischemia, and Alzheimer's disease. Research indicates NGF's pivotal involvement in traumatic brain injury (TBI). Animal models such as fluid percussion and weight-drop impact models were employed to explore TBI pathology, pathophysiology, and treatment. In these models, NGF, in correlation with other NTFs, significantly increased post-TBI, sustained by glucocorticoids and neuroactive steroid progesterone but inhibited by hypothermia. NGF exhibits neuroprotective effects in TBI, attenuating brain edema, activating antioxidants, inhibiting neuron loss, and alleviating amyloid β42 (Aβ42) deposition. Early up-regulation of NGF in children's cerebral spinal fluid (CSF) 2 hours post-TBI correlates with injury severity and improved functional outcomes. Various TBI treatments, such as marrow stem cells (MSCs), NT2N implantation, and hyperbaric oxygen (HBO) treatment, correlate with changes in NGF expression. Additionally, NGF and Brain-Derived Neurotrophic Factor (BDNF) promote MSC migration and differentiation in vivo. Despite two decades of research on NGF in TBI models, there is a lack of persuasive evidence regarding its function and mechanism. The limited use of transgenic animals or RNA interference for NGF hinders investigations. Effective treatment of TBI with NGF-related strategies is still a significant challenge.

Serum levels of soluble receptor activator of NF-κβ ligand are under dual, immune and neural effects in postmenopausal women

Background: The receptor activator of NF-κβ (RANK)/RANK ligand/ osteoprotegerin system is essential for osteoclast maturation and activation to induce bone loss, which plays a role in postmenopausal osteoporosis. Estrogen deficiency in postmenopausal women is associated with T-cell mediated inflammation with increased proinflammatory cytokines, such as IL-17A, IL-1, IL-6 and tumor necrosis factor alpha. Bone repair and remodeling processes highlight the role of nerve growth factor β (NGFβ), whose non-neural production is associated with T-cell mediated inflammation. Aims: To investigate the involvement of IL-17A and NGFβ cytokines in the elevation of serum soluble RANK ligand levels in postmenopausal and control women. Methods: Fifty-two postmenopausal and 37 control women were studied for age, body mass index, homeostasis model assessment (HOMA) index, serum levels of IL-17A, NGFβ, soluble RANK ligand (measured by indirect enzyme-linked immunosorbent assay) and estrogen (measured by chemiluminescence assay). Two- and three-way ANOVA (expressed as median with Q1 to Q3) and linear regression analysis were used to evaluate the strength of relationship between soluble RANK ligand levels as dependent and age, serum IL-17A and NGFβ levels as independent variables. Results: A significant difference in age, serum NGFβ and estrogen levels could be demonstrated between postmenopausal and control women (with borderline significance in HOMA indices). The differences in serum IL-17A and NGFβ levels were relevant between categories for body mass index in postmenopausal and control women, but in soluble RANK ligand levels only in postmenopausal women. The increase in soluble RANK ligand levels was greater in elevated IL-17A [101(291.75 to 39.92) vs. 45.24(95.56 to 25.34) ng/ml, p<0.015] and elevated NGFβ [222.2(142.75 to 1086.87) vs. 52.44(25.87 to 76.88) ng/ml, p<0.0001] categories compared to low categories in postmenopause, but not in controls. Both elevated IL-17A and NGFβ levels resulted in the greatest increase in serum levels of soluble RANK ligand [252.27(159.9 to 1099.64) vs. 41.4(35.91 to 59.94) ng/ml, p<0.0001] compared to elevated IL-17A levels alone. Conclusion: Both IL-17A and NGFβ cytokines were involved in the increased serum levels of soluble RANK ligand in postmenopausal women. Their joint involvement in postmenopausal osteoporosis highlighted that neurogenic inflammation may play a critical role in bone loss via greater elevated soluble RANK ligand levels induced by concomitant elevated IL-17A and NGFβ levels.

Nerve Growth Factor/Tyrosine Kinase A Receptor Pathway Enhances Analgesia in an Experimental Mouse Model of Bone Cancer Pain by Increasing Membrane Levels of δ-Opioid Receptors.

The role of nerve growth factor (NGF)/tyrosine kinase A receptor (TrKA) signaling, which is activated in a variety of pain states, in regulating membrane-associated δ-opioid receptor (mDOR) expression is poorly understood. The hypothesis was that elevated NGF in bone cancer tumors could upregulate mDOR expression in spinal cord neurons and that mDOR agonism might alleviate bone cancer pain. Bone cancer pain (BCP) was induced by inoculating Lewis lung carcinoma cells into the femoral marrow cavity of adult C57BL/6J mice of both sexes. Nociceptive behaviors were evaluated by the von Frey and Hargreaves tests. Protein expression in the spinal dorsal horn of animals was measured by biochemical analyses, and excitatory synaptic transmission was recorded in miniature excitatory synaptic currents. The authors found that mDOR expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.18 ± 0.01 g vs. mean ± SD: 0.13 ± 0.01 g, n = 4, P < 0.001) and that administration of the DOR agonist deltorphin 2 (Del2) increased nociceptive thresholds (Del2 vs. vehicle, median [25th, 75th percentiles]: 1.00 [0.60, 1.40] g vs. median [25th, 75th percentiles]: 0.40 [0.16, 0.45] g, n = 10, P = 0.001) and reduced miniature excitatory synaptic current frequency in lamina II outer neurons (Del2 vs. baseline, mean ± SD: 2.21 ± 0.81 Hz vs. mean ± SD: 2.43 ± 0.90 Hz, n = 12, P < 0.001). Additionally, NGF expression was increased in BCP mice (BCP vs. sham, mean ± SD: 0.36 ± 0.03 vs. mean ± SD: 0.16 ± 0.02, n = 4, P < 0.001), and elevated NGF was associated with enhanced mDOR expression via TrKA signaling. Activation of mDOR produces analgesia that is dependent on the upregulation of the NGF/TrKA pathway by increasing mDOR levels under conditions of BCP in mice.

Role of nerve growth factor on cognitive impairment in patients with Alzheimer's disease carrying apolipoprotein E ε4.

To investigate the roles of neurotrophic factors on cognition in patients with Alzheimer's disease (AD) carrying Apolipoprotein E (APOE) ε4. Totals of 173 patients with AD were divided into APOE ε4 carrier and non-carrier groups, and their demographics, cognition, and neurotrophic factors in cerebrospinal fluid (CSF) were compared. Multiple linear regression analyses were performed to assess correlations among APOE ε4, neurotrophic factors and cognition. Mediation analyses were conducted to assess the sequential associations among APOE ε4, nerve growth factor (NGF), and cognition. Global cognition and multiple domains were impaired in the APOE ε4 carrier group (all p < 0.05). NGF level in the APOE ε4 carrier group was lower than that in the non-carrier group (p = 0.016). NGF level showed significant correlations with both global and multiple domains cognitions. Specifically, NGF mediated the association between APOE ε4 and Animal Fluency Test score (β, -0.45; 95% CI [-0.96, -0.07]; p < 0.001) and Trail Making Test-A (time) (β, 0.15; 95% CI [0.01, 0.33]; p < 0.001). APOE ε4 is associated with cognitive impairment, and those carrying APOE ε4 have decreased NGF level in CSF. Declined NGF level is correlated with compromised cognition. NGF mediates APOE ε4-associated cognitive impairment.

A Possible Role for Nerve Growth Factor and Its Receptors in Human Sperm Pathology.

Nerve growth factor (NGF) signalling affects spermatogenesis and mature sperm traits. In this paper, we aimed to evaluate the distribution and the role of NGF and its receptors (p75NTR and TrKA) on the reproductive apparatus (testis and epididymis) and sperm of fertile men (F) and men with different pathologies, namely varicocele (V) and urogenital infections (UGIs). We collected semen samples from 21 individuals (31-40 years old) subdivided as follows: V (n = 7), UGIs (n = 7), and F (n = 7). We submitted the semen samples to bacteriological analysis, leucocyte identification, and analysis of sperm parameters (concentration, motility, morphology, and viability). We determined the seminal plasma levels of NGF, interleukin 1β (IL-1β), and F2-isoprostanes (F2-IsoPs), and the gene and protein expression of NGF receptors on sperm. We also used immunofluorescence to examine NGF receptors on ejaculated sperm, testis, and epididymis. As expected, fertile men showed better sperm parameters as well as lower levels of NGF, F2-IsoPs, and IL-1β compared with men with infertility. Notably, in normal sperm, p75NTR and TrKA were localised throughout the entire tail. TrKA was also found in the post-acrosomal sheath. This localisation appeared different in patients with infertility: in particular, there was a strong p75NTR signal in the midpiece and the cytoplasmic residue or coiled tails of altered ejaculated sperm. In line with these findings, NGF receptors were intensely expressed in the epididymis and interstitial tissue of the testis. These data suggest the distinctive involvement of NGF and its receptors in the physiology of sperm from fertile men and men with infertility, indicating a possible role for new targeted treatment strategies.

THE NOOTROPIC EFFECT OF A DIPEPTIDE MIMETIC OF NGF IN AN EXPERIMENTAL MODEL OF ALZHEIMER'S DISEASE

Relevance. The role of nerve growth factor (NGF) deficiency in the pathogenesis of Alzheimer's disease (AD) is well-known. The clinical application of full-size neurotrophin is limited due to its low bioavailability and the risk of adverse effects. At the V.V. Zakusov Institute of Pharmacology, a dimeric di-peptide mimetic of the 4th loop of NGF, compound GK-2 (hexamethylenediamide bis-(N-monosuccinyl-L-glutamyl-L-lysine), was created. It selectively activates specific TrkA receptors and possesses neuroprotective and neuroregenerative properties. Additionally, GK-2 lacks the main side effects of NGF, namely hyperalgesia and weight loss. The aim of the current study was to investigate the influence of GK-2 on rat memory under the conditions of the scopolamine-induced model of AD. Material and Methods. Scopolamine was administered intraperitoneally to rats at a dose of 2 mg/kg for 32 days. Simultaneously with scopolamine, animals were intraperitoneally injected with GK-2 at doses of 0.5 and 1 mg/kg. Following the administration of the compounds, a novel object recogni-tion test was conducted to assess both short-term and long-term memory. Results. Rats receiving scopolamine exhibited a statistically significant decline in long-term memory. The dipeptide GK-2 at a dose of 1 mg/kg com-pletely counteracted the development of this impairment. Conclusion. The dipeptide mimetic of nerve growth factor, GK-2, shows promise for further investigation as a potential therapeutic agent for the treatment of AD.

The role of nerve growth factor (NGF) in the pathogenesis of leprosy

Leprosy is a chronic infectious disease caused by M. leprae with a primary lesion of the skin and peripheral nervous system. Currently, clinicians using bacterioscopic studies of scarification and skin biopsy mainly diagnose leprosy. However, the development and application of new diagnostic criteria, especially those associated with damage to nerve fibers, remains an urgent task of modern leprology. This review considers the important role of neurotrophic factor (nerve growth factor, NGF) in the pathogenesis of nervous system damage in leprosy and establishes the relationship between NGF levels and forms of the disease. The review includes data from foreign and domestic articles; the search was carried out using the “Scopus”, “PubMed”, “Web of Science”, “elIBRARY” databases.

Vortioxetine attenuates pain hypersensitivity in female rats with monoiodoacetate-induced osteoarthritis: role of nerve growth factor

Vortioxetine attenuates pain hypersensitivity in female rats with monoiodoacetate-induced osteoarthritis: role of nerve growth factor

NGF and the Male Reproductive System: Potential Clinical Applications in Infertility.

Infertility is a worldwide health issue defined by the World Health Organization (WHO) as the inability to establish a pregnancy after 12 months or more of regular and unprotected sexual intercourse. Male infertility etiology can be related to either congenital or acquired factors. The therapeutical approach to male infertility depends on the underlying causes and includes medical and surgical treatments. In recent studies, the potential role of nerve growth factor (NGF) in male reproductive physiology has been proposed. It has been hypothesized that neurotrophins might be involved in testis morphogenesis and regulation of several aspects of spermatogenesis. Moreover, it has been shown that NGF exerts its role on gonadotropin-releasing hormone (GnRH) neurons through the activation of the PKC/p-ERK1/2/p-CREB cascade, which leads to the activation of hypothalamic cells and the consequent activation of hypothalamus-pituitary-gonadal axis (HPG) with the secretion of GnRH. Lastly, it has been shown that the physiology of mature sperm is affected by both exogenous and endogenous NGF. The NGF impact on the HPG axis and its effect on GnRH neurons might be exploited in the therapy of male hypogonadism or used as a protective strategy against gonadal dysfunction related to chemotherapeutic agents. Moreover, the improving effect of NGF on sperm motility and vitality could be useful to enhance assisted reproduction outcomes. NGF could be supplemented to cryopreserved sperm samples to counteract the oxidative stress induced by the frozen and thawing processes. Indeed, the potential clinical applications of NGF in male infertility treatment have been discussed.

NGF/TrkA promotes the vitality, migration and adhesion of bone marrow stromal cells in hypoxia by regulating the Nrf2 pathway.

Bone marrow stromal cells (BMSCs) transplantation is a treatment strategy for ischemic stroke (IS) with great potential. However, the vitality, migration and adhesion of BMSCs are greatly impaired due to the harsh environment of the ischemic area, which affects the therapeutic effects. Herein, we aimed to investigate the roles of nerve growth factor (NGF) in regulating cell behaviors of BMSCs in IS. The mRNA and protein expressions were assessed using qRT-PCR and western blot, respectively. To simulate ischemic-like conditions in vitro, Brain microvascular (bEnd.3) cells were exposed to oxygen and glucose deprivation (OGD). Cell viability and cell proliferation were evaluated by MTT assay and BrdU assay, respectively. Transwell migration and cell adhesion assays were carried out to determine cell migration and adhesion of BMSCs, respectively, coupled with flow cytometry to evaluate cell apoptosis of bEnd.3 cells. Finally, angiogenesis assay was performed to assess the angiogenesis ability of bEnd.3 cells. NGF overexpression resulted in increased cell vitality, adhesion and migration of BMSCs, while NGF knockdown presented the opposite effects. We subsequently discovered that TrkA was a receptor for NGF, and TrkA knockdown significantly inhibited the cell viability, migration and adhesion of BMSCs. Besides, Nrf2 was confirmed as the downstream target of NGF/TrkA to promote the viability, adhesion and migration of BMSC cells. Finally, NGF-silenced BMSCs could not effectively restore the OGD-induced brain microvascular cell damage. NGF/TrkA promoted the viability, migration and adhesion of BMSCs in IS via activating Nrf2 pathway.

The Role of Nerve Growth Factor in Alergic Reactions and Healing Process of Tissues

Nerve growth factor is a protein which regulates the differentiation and survival of nerve system. It is produced in neurons and in several non-nervous cells which are involved in some inflammatory and immunological states. These cells include mast cells, lymphocytes, macrophages and fibroblasts. Mast cells play a crucial role in the inflammatory and allergic reactions. Inflammatory cells express specific receptors for binding NGF, tyrosine kinase (TrkA) receptor. Binding of nerve growth factor to this receptor activates the immune cells. Activation of the cells leads to secretion of many inflammatory mediators from them. The mediators (histamine, serotonin, tryptase and some interlevkines) are involved in the early response of inflammatory cells. The cytokines and growth factors produced later in the inflammatory process activate fibroblasts and other cells, which participate in healing process of tissues.

CLOSING THE GAP FOR PHARMACOLOGICAL TREATMENT OF PAINFUL DIABETIC NEUROPATHY : THE POTENTIAL ROLE OF VITAMIN D

Painful neuropathic pain is a challenging chronic pain to treat. It is heterogeneous in symptoms and could be resistant to the available treatments regimen. Current pharmacological treatments fail to achieve adequate pain relief in a most patients. The previous review showed that only less than 50% of patients can achieve good pain reduction with standard adjuvant treatment. The available adjuvants analgesic only focus in the symptom control, and do not interfere with the progressing damage of the nerve. Vit D insufficiency is quite frequent in type 2 diabetes patients.diabetes, particularly those with symptoms of DPN. The studies also showed that low serum vitamin D levels are an independent predictor of DPN development. Vitamin D supplementation is necessary for diabetic neuropathy patients since it promotes the synthesis of neurotrophins and neurotransmitters. Additional vitamin D therapy have big role in nerve growth factor and the regulation of neurotrophin and Ca2+ homeostasis in neurons, and provides protection for neurons in the peripheral nervous system. In this review, we do systematically search the studies about Vitamin D for the treatment of painful diabetic neuropathic condition. We used PubMed, Cochrane, Clinical Key, and search Google Scholar for papers that used vitamin D phrases. and painful diabetic neuropathy as our major database for this review and we make a systematic table to explain our review. However, there is still an unmet need in the management of neuropathic pain. The unmet needs maybe caused by the gap between pharmacological treatmnet in pain reduction in painful diabetic neuropathy patients. Therefore, in this review we discuss about the potential use of vitamin D as an add-on therapy to closing the gap in the management of neuropathic pain.

Ultrasound delivery of a TrkA agonist confers neuroprotection to Alzheimer-associated pathologies.

Early degeneration of basal forebrain cholinergic neurons contributes substantially to cognitive decline in Alzheimer’s disease. Evidence from preclinical models of neuronal injury and aging support a pivotal role for nerve growth factor (NGF) in neuroprotection, resilience, and cognitive function. However, whether NGF can provide therapeutic benefit in the presence of Alzheimer’s disease-related pathologies still unresolved. Perturbations in the NGF signalling system in Alzheimer’s disease may render neurons unable to benefit from NGF administration. Additionally, challenges related to brain delivery remain for clinical translation of NGF-based therapies in Alzheimer’s disease. To be safe and efficient, NGF-related agents should stimulate the NGF receptor, tropomyosin receptor kinase A (TrkA), avoid activation through the p75 neurotrophin receptor (p75NTR), and be delivered non-invasively to targeted brain areas using real-time monitoring. We addressed these limitations using MRI-guided focused ultrasound (MRIgFUS) to increase blood–brain barrier permeability locally and transiently, allowing an intravenously administered TrkA agonist that does not activate p75NTR, termed D3, to enter targeted brain areas. Here, we report the therapeutic potential of selective TrkA activation in a transgenic mouse model that recapitulates numerous Alzheimer’s disease-associated pathologies. Repeated MRIgFUS-mediated delivery of D3 (D3/FUS) improved cognitive function in the TgCRND8 model of Alzheimer’s disease. Mechanistically, D3/FUS treatment effectively attenuated cholinergic degeneration and promoted functional recovery. D3/FUS treatment also resulted in widespread reduction of brain amyloid pathology and dystrophic neurites surrounding amyloid plaques. Furthermore, D3/FUS markedly enhanced hippocampal neurogenesis in TgCRND8 mice, implicating TrkA agonism as a novel therapeutic target to promote neurogenesis in the context of Alzheimer’s disease-related pathology. Thus, this study provides evidence that selective TrkA agonism confers neuroprotection to effectively counteract Alzheimer’s disease-related vulnerability. Recent clinical trials demonstrate that non-invasive blood–brain barrier modulation using MRIgFUS is safe, feasible and reversible in Alzheimer’s disease patients. TrkA receptor agonists coupled with MRIgFUS delivery constitute a promising disease-modifying strategy to foster brain health and counteract cognitive decline in Alzheimer’s disease.

CS nerve growth factor regulates sevoflurane anesthesiainduced nerve injury in nerve cells

Purpose: Sevoflurane is the most commonly used anesthetic agent for surgery. However, it is associated with deficiency in learning and memory abilities. The study was aimed at investigating the role of nerve growth factor (NGF) in sevoflurane anesthesia-induced nerve injury.Methods: RT-qPCR assay was applied to measure expressions of NGF, miR-98-5p and other factors related to apoptosis. CCK-8 assay was used for detecting cell viability while luciferase reporter assay was employed to measure binding condition between miR-98-5p and NGF. Expressions of proteins in PI3K/AKT/mTOR signaling pathway was measured with western blot.Results: Sevoflurane reduced cell viability of RGC-5 cells, promoted apoptosis and reduced the expression of NGF. In sevoflurane-induced RGC-5 cells, over-expression of NGF promoted cell viability with reduced apoptosis. Also, there was reduction in the protein expression of PI3K/AKT/mTOR signaling pathway by sevoflurane, while up-regulation of NGF promoted the expressions of these proteins. In the presence of PI3K inhibitor, reduction cell viability was reduced but apoptosis increased. Luciferase reporter assay detected MiR-98-5p as the target gene of NGF and its overexpression restored high cell viability in the over-expressed NGF. The rate of apoptosis and expressions of proteins was also restored with up-regulation of miR-98-5p.Conclusion: Sevoflurane caused damage to nerve cells, while over-expression of NGF reduced the injury through PI3K/AKT/mTOR signaling pathway and suppression of miR-98-5p.&#x0D; Keywords: Nerve growth factor, Sevoflurane, Nerve injury, Anesthesia, miR-98-5p

The Versatile Roles of Nerve Growth Factor in Neuronal Attraction, Odontoblast Differentiation, and Mineral Deposition in Human Teeth.

Nerve growth factor (NGF) is an important molecule for the development and differentiation of neuronal and non-neuronal cells. Here we analyze by immunohistochemistry the distribution of NGF in the dental pulp mesenchyme of embryonic and functional human teeth. In the dental pulp of both embryonic and healthy functional teeth, NGF is mainly expressed in the odontoblasts that are responsible for dentine formation, while in functional teeth NGF is also expressed in nerve fibers innervating the dental pulp. In injured teeth, NGF is expressed in the newly formed odontoblastic-like cells, which replace the dying odontoblasts. In these teeth, NGF expression is also upregulated in the intact odontoblasts, suggesting a role for this molecule in dental tissue repair. Similarly, in cultures of human dental pulp cells, NGF expression is strongly upregulated during their differentiation into odontoblasts as well as during the mineralization process. In microfluidic devices, release of NGF from cultured human dental pulp cells induced neuronal growth from trigeminal ganglia toward the NGF secreting cells. These results show that NGF is closely linked to the various functions of odontoblasts, including secretory and neuronal attraction processes.

Role of nerve growth factor in the reproductive physiology of female rabbits: A review

Rabbit does are reflex ovulators such that coitus is needed to release GnRH and elicit the LH surge that triggers the ovulation of mature oocytes. However, the mechanisms eliciting ovulation in this species remain unclear. One of the most promising recently discovered candidates with a role in female reproductive physiology is nerve growth factor beta (β-NGF). This neurotrophin and its high-affinity receptor TrkA and low affinity receptor p75, is present in all compartments of the ovary, oviduct and uterus suggesting a physiologic role in ovarian folliculogenesis, steroidogenesis, ovulation, luteogenesis and embryo development. Besides, evidence exists that β-NGF found in seminal plasma could exert a modulatory role in the female hypothalamus-pituitary-ovarian axis contributing to the adrenergic and cholinergic neuronal stimulus of GnRH neurons in an endocrine manner during natural mating. Probably, the paracrine and local roles of the neurotrophin in steroidogenesis and ovulation reinforce the neuroendocrine pathway that leads to ovulation. This review updates knowledge of the role of β-NGF in rabbit reproduction, including its possible contribution to the mechanisms of action that induce ovulation, and discusses perspectives for the future applications of this neurotrophin on rabbit farms.

Hypomethylation of nerve growth factor (NGF) promotes binding of C/EBP\u03b1 and contributes to inflammatory hyperalgesia in rats

BackgroundChronic pain usually accompanied by tissue damage and inflammation. However, the pathogenesis of chronic pain remains unclear.MethodsWe investigated the role of nerve growth factor (NGF) in chronic inflammatory pain induced by complete Freund’s adjuvant (CFA), explored the methylation status of CpG islands in the promoter region of the NGF gene, and clarified the function and mechanism of C/EBPα-NGF signaling pathway from epigenetic perspective in the chronic inflammatory pain model.ResultsCFA induced significant hyperalgesia and continuous upregulation of NGF mRNA and protein levels in the L4–6 dorsal root ganglions (DRGs) in rats. Hypomethylation of CpG islands occurred in the NGF gene promoter region after CFA treatment. At the same time, the miR-29b expression level was significantly increased, while the DNA methyltransferase 3b (DNMT3b) level reduced significantly. Moreover, CFA treatment promoted binding of C/EBPα to the NGF gene promoter region and C/EBPα siRNA treatment obviously decreased expression of NGF levels and also alleviate inflammatory hyperalgesia significantly in rats.ConclusionCollectively, the results indicated that CFA leads to the upregulation of miR-29b level, which represses the expression of DNMT3b, enhances the demethylation of the NGF gene promoter region, and promotes the binding of C/EBPα with the NGF gene promoter, thus results in the upregulation of NGF gene expression and maintenance of chronic inflammatory pain.