OBJECTIVETo investigate the expressions of neurotrophic factors (NTFs) and their receptors in prostate cancer.

METHODSWe detected the expressions of the nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and their receptors TrkA, TrkB and p75 in 35 specimens of prostate cancer by Western blotting, and included 10 specimens of normal prostate tissue from young males that died accidentally.

RESULTSCompared with the control group, the expressions of NGF and p75 were significantly decreased (P < 0.01), while those of BDNF, TrkA and TrkB significantly increased in prostate cancer (P < 0.05).

CONCLUSIONThe changes in the expressions of NTFs and their receptors were related with the pathogenesis and progression of prostate cancer, which may be considered as reference indexes for the diagnosis of the disease.

Adolescent ; Adult ; Aged ; Brain-Derived Neurotrophic Factor ; metabolism ; Case-Control Studies ; Humans ; Male ; Middle Aged ; Nerve Growth Factors ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; Receptor, Nerve Growth Factor ; metabolism ; Receptor, trkA ; metabolism ; Receptor, trkB ; metabolism ; Young Adult

TrkA is essential components of the high-affinity NGF receptor necessary to mediate biological effects of the neurotrophins NGF. Here we report on the expression of trkA in the cerebral cortex and diencephalon of mongolian gerbils during postnatal development. The expression of trkA was identified by immunohistochemical method. In parietal cortex and piriform cortex, higher levels of trkA-IR (immunoreactivity) were detected at 3 days postnatal (P3) and at P9. Although trkA was not expressed till P3 in the parietal cortex, it was detectable at birth in the piriform cortex. Several regions, such as Layers I, IV & VI, did not show much expression. Layer I showed especially weak labeling. In the hippocampus, thalamus, and hypothalamus, higher levels of trkA-IR were detected at P6 and P12 than earlier days. But trkA was not expressed at birth in the hippocampus, at P3 in the reticular thalamic nucleus (Rt), or neonatally in the dorsomedial hypothalamic nucleus (DM). This data shows that expression of trkA is developmentally regulated and suggests that high affinity neurotrophin-receptors mediate a transient response to neurotrophines in the cerebral cortex and diencephalon during mongolian gerbil brain ontogeny.
Animals ; Animals, Newborn ; Cerebral Cortex/*metabolism ; Diencephalon/*metabolism ; Gerbillinae/*metabolism ; Immunohistochemistry/veterinary ; Nerve Growth Factor/metabolism ; Receptor, trkA/*metabolism

OBJECTIVETo investigate the nerve growth factor (NGF) regulating the expression of calcitonin gene-related peptide (CGRP) in promoting the proliferation of osteoblast-like cell (MG-63) and thus illustrate the mechanism of the NGF in wound healing.

METHODSDifferent concentrations of NGF were used to stimulate MG-63. The expression of CGRP was detected by real-time quantitative polymerase chain reaction (RT-QPCR) and enzyme-linked immunosorbent assay after 1, 2, 3, and 4 days. The proliferation of MG-63 was detected by cell counting kit-8 (CCK-8). The expression of CGRP mRNA and the proliferation of MG-63 were then detected by RT-QPCR and CCK-8 after adding the NGF receptor blocker.

RESULTSCompared with the blank control group, the expression of CGRP significantly increased by stimulating the NGF. The expression of CGRP was positively related to the concentration of NGF (P<0.05). Moreover, the expression of CGRP increased by prolonging the NGF stimulation time. The proliferation of MG-63 increased after stimulating the NGF (P<0.05). After adding the NGF receptor blocker, the expression of CGRP and the proliferation of MG-63 correspondingly decreased (P<0.05).

CONCLUSIONNGF can up-regulate the expression of CGRP and increase the proliferation of MG-63. Therefore, NGF plays a significant role in wound healing.

Animals ; Calcitonin ; Calcitonin Gene-Related Peptide ; metabolism ; Cell Line ; Ganglia, Spinal ; Humans ; Nerve Growth Factor ; metabolism ; Rats, Sprague-Dawley ; Receptor, Nerve Growth Factor ; Signal Transduction ; Up-Regulation

Nerve growth factor (NGF) is mainly secreted by the neuroglia cells, which can exert biological effect through its receptors on the specific target cell surface. NGF is closely related to neurocyte growth, differentiation and apoptosis. As a neurotropic virus, HSV-1 an easily lead to neurocyte, neuroglia cells death or apoptosis. In this study, the U251 human glioma cells were chosen as target cells to study the change of NGF and its receptors in the apoptosis process of HSV-1 infection. Our results showed that U251 cells were permissive to HSV-1 replication. In the apoptosis process of HSV-1 infected U251 cells, the expression of both NGF and P75NTR increased and then decreased, while the expression of TrkA decreased gradually. These result indicated that HSV-1 was able to induce the abnormal expression of NGF and its receptors in U251 cells.
Apoptosis ; Cell Line, Tumor ; Gene Expression ; Glioma ; genetics ; metabolism ; physiopathology ; virology ; Herpes Simplex ; genetics ; metabolism ; physiopathology ; virology ; Herpesvirus 1, Human ; genetics ; physiology ; Humans ; Nerve Growth Factor ; genetics ; metabolism ; Receptor, Nerve Growth Factor ; genetics ; metabolism ; Receptor, trkA ; genetics ; metabolism ; Virus Replication

OBJECTIVE: To determine the expression of nerve growth factor (NGF), tyrosine kinase receptor A (trkA), and pan-neurotrophin receptor (p75) in the lung tissues in asthmatic rats, and to explore their effects on the airway inflammation. METHODS: Thirty-two SD rats were randomly divided into 4 groups: the control, asthma, NGF and anti-NGF groups. The asthmatic model was established by the inhalation and injection of ovalbumin. The total cell count and differential cell count in the bronchoalveolar lavage fluid (BALF) were performed. The pathologic changes in the lung tissues of the 4 groups was detected by HE staining. The NGF mRNA expression in the lung tissues of the asthma and control groups was determined by reverse transcription-polymerase chain reaction (RT-PCR). The changes of trkA and p75 mRNA expressions in the lung tissues in the 4 groups were also investigated by RT-PCR. RESULTS: Compared with the control group, the BALF total cell, the BALF eosinophils (Eos), and the BALF lymphocytes (Lyms) significantly increased (All P <0. 001) in the asthma group; and the lung tissues of the asthma group had more infiltrating inflammatory cells. Not only the expression of NGF mRNA, but also its receptors trkA and p75 mRNA in the lung tissues were significantly higher in the asthma group than those in the control group (All P < 0.01). Positive correlation was found between the expression of NGF mRNA and the BALF total cell, the BALF Lyms in the asthma group. Compared with the asthma group, the total cell, the Eos, and the lyms in BALF in the NGF group significantly increased (All P < 0.01), and the lungs of the NGF group had apparent inflammatory changes. The expre-ssions of p75 and trkA mRNA were enhanced significantly (All P < 0.05). Compared with the asthma group, the total cell, the Eos, and the lyms in BALF in the anti-NGF group significantly decreased (All P < 0.001), and the lungs of the anti-NGF group showed alleviative inflammatory changes. The expre-ssions of p75 and trkA mRNA significantly decreased (All P < 0.01). CONCLUSION In lungs of asthmatic rats, the elevated expression of NGF mRNA is closely related to the airway inflammation. NGF can upregulate the expressions of p75 and trkA mRNA in asthmatic rats, and then may promote their role in the airway neuronal inflammation in asthma.
Animals ; Asthma ; chemically induced ; metabolism ; Bronchitis ; metabolism ; Lung ; metabolism ; Male ; Nerve Growth Factor ; metabolism ; Ovalbumin ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, trkA ; metabolism ; Receptors, Nerve Growth Factor ; metabolism

OBJECTIVETo investigate the expressions and action mechanisms of nerve growth factor (NGF) receptors TrkA and p75NTR in the oncogenesis and progression of prostate cancer (PCa).

METHODSUsing immunohistochemistry, we detected the expressions of TrkA and p75NTR in 62 PCa and 35 benign prostatic hyperplasia (BPH) samples, and conducted statistical analysis on the basis of clinical data.

RESULTSIndependent-samples t-test showed that, along with poorer tissue differentiation or higher clinical stage of PCa, the expression of TrkA was significantly up-regulated, that of p75NTR remarkably down-regulated, and the expression ratio of TrkA to p75NTR markedly increased. The TrkA/p75NTR ratio was 0.32 in the BPH, 0.52 in the PCa tissue with Gleason score of 6, 1.65 in the PCa tissue with Gleason score of 7, 5.75 in the PCa tissue with Gleason score ≥ 8, 0.89 in the clinical stage of pT2, 1.5 in pT3 a, 3.75 in pT3b, and 7.00 in pTxN1.

CONCLUSIONThe abnormally increased expression ratio of TrkA to p75NTR might be one of the essential features of malignant transformation of prostate cells. A higher TrkA/p75NTR expression ratio may be associated with a lower tissue differentiation, a higher clinical stage or Gleason score, and therefore a poorer prognosis.

Humans ; Immunohistochemistry ; Male ; Neoplasm Grading ; Neoplasm Staging ; Nerve Tissue Proteins ; metabolism ; Prognosis ; Prostatic Hyperplasia ; pathology ; Prostatic Neoplasms ; pathology ; Receptor, trkA ; metabolism ; Receptors, Nerve Growth Factor ; metabolism ; Up-Regulation

OBJECTIVETo investigate the effect of diabetic autonomic neuropathy on the seminal vesicle and search for the theoretical evidence for the prevention and treatment of diabetic infertility by observing changes in the contents of the nerve growth factor (NGF) and muscarinic M3 receptor in the seminal vesicle of diabetic rats.

METHODSDiabetic models were established in 10 of the 15 male adult SD rats by intraperitoneal injection of streptozotocin (STZ), and the other 5 were included in a normal control group. Eight weeks after modeling, seminal vesicles were collected from the rats for HE and immunohistochemical staining.

RESULTSCompared with the normal controls, the diabetic models showed a decreased number of smooth muscle cells, thinner cytoplasm of glandular epithelial cells and disordered structure in the seminal vesicle. The intensity of NGF-positive staining was significantly enhanced, but that of M3 markedly reduced in the diabetic group. There were statistically significant differences in the mean integrated optical density (IA) of muscarinic M3 receptors and NGF between the control and diabetic groups (0.0187 +/- 0.0024 vs 0.0100 +/- 0.0015 and 0.0209 +/- 0.0085 vs 0.0412 +/- 0.0117, P<0.01).

CONCLUSIONThe changes in the expressions of NGF and M3 receptors in the seminal vesicle of diabetic rats suggest that diabetes mellitus may induce autonomic neuropathy of the seminal vesicle.

Animals ; Diabetes Mellitus, Experimental ; metabolism ; Male ; Nerve Growth Factor ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Muscarinic M3 ; metabolism ; Seminal Vesicles ; metabolism

Motor units comprise a motoneuron and the muscle fibers it innervates. Neuromuscular transmission is tightly regulated to match the activity of individual motor units. Activity-dependent release of neuromodulators at the neuromuscular junction (NMJ) determines the efficacy of transmission. The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) are produced by motoneurons and muscle fibers, and their release by skeletal muscle is regulated by muscle activity. BDNF and NT-4 enhance both spontaneous and evoked synaptic transmission at NMJs via activation of the tyrosine kinase receptor B (TrkB). Improvements in neuromuscular transmission may result from increased release of synaptic vesicles, either by presynaptic alterations in Ca(2+) transients or facilitated vesicular exocytosis. In fact, BDNF potentiates intracellular Ca(2+) release presynaptically and BDNF-induced TrkB activation also results in phosphorylation of synapsin I via mitogen activated protein kinase, which increases the number of synaptic vesicles available for release. Neurotrophins may also regulate synaptic transmission at the NMJ by increasing local release of neuregulin or other nerve-derived modulators. We review recent studies on the regulation of neuromuscular transmission, the motor unit-specific properties of NMJs and the effects of neurotrophins on synaptic efficacy at the NMJ.
Animals ; Brain-Derived Neurotrophic Factor ; physiology ; Calcium ; metabolism ; Humans ; Nerve Growth Factors ; physiology ; Neuromuscular Junction ; physiology ; Neuronal Plasticity ; Receptor, trkB ; metabolism ; Synapses ; metabolism ; Synapsins ; metabolism ; Synaptic Vesicles

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD). METHODS: Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg^-1•d^-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1β (IL-1β) in duodenum was measured by ELISA. RESULTS: Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1β in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1β in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01). CONCLUSION EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.
Acupuncture Points ; Animals ; Duodenum/metabolism* ; Dyspepsia/therapy* ; Electroacupuncture ; Ketotifen ; Mast Cells/metabolism* ; Nerve Growth Factor/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Receptor, trkA/genetics*

OBJECTIVETo study the mechanism of brain development delay in rats with intrauterine growth retardation (IUGR) by examining the expression of nerve growth factor (NGF) and tyrosine kinase receptor A (Trk A) in the brain.

METHODSThirty-two pregnant rats were randomly fed with a normal diet (control group) or lower protein diet (IUGR group) during pregnancy (n=16 each). The pup rats were sacrificed at 0, 7, 14 or 21 days after birth. The protein levels of NGF and TrkA in the brain were determined by Western blot and immunohistochemistry staining.

RESULTSThe levels of NGF and TrkA in the brain in pup rats of the IUGR group were significantly lower than those in the control group 0, 7, 14 and 21 days after birth.

CONCLUSIONSThe decreased expression of protein levels of NGF and TrkA in the brain might be one of the causes of brain development delay in IUGR rats.

Animals ; Birth Weight ; Brain Chemistry ; Female ; Fetal Death ; epidemiology ; Fetal Growth Retardation ; epidemiology ; metabolism ; Immunohistochemistry ; Nerve Growth Factor ; analysis ; Pregnancy ; Rats ; Rats, Wistar ; Receptor, trkA ; analysis