The neurotrophin-tyrosine receptor kinase B (TrkB) signaling pathway plays an important role in regulating the balance of excitation and inhibition in the primary visual cortex (V1). Previous studies have revealed its mechanism of regulating the level of cortical excitability by increasing the efficiency of excitatory transmission, but it has not been elucidated how TrkB receptors regulate the balance of excitation and inhibition through the inhibitory system, which in turn affects visual cortex function. Therefore, the objective of this study was to investigate how the TrkB signaling pathway specifically regulates the most important inhibitory neuron-PV neurons affects the visual cortex function of mice. The expression of TrkB receptor on PV neurons in the V1 region was specifically reduced by the virus, the functional changes of inhibitory and excitatory neurons in the primary visual cortex were recorded by multi-channel electrophysiological in vivo. The orientation discrimination ability of mice was tested by behavioral experiments, and altered orientation discrimination ability of mice was tested by behavioral experiments. The results showed that reduced expression of TrkB receptors on PV inhibitory neurons in primary visual cortex significantly increased the response intensity of excitatory neurons, reduced the orientation discrimination ability of inhibitory and excitatory neurons, and increased the signal-to-noise ratio, but the orientation discrimination ability at the individual level in mice showed a decrease. These results suggest that the TrkB signaling pathway does not modulate the function of PV neurons solely by increasing excitatory transmission targeting PV neurons, and its effect on neuronal signal-to-noise ratio is not due to enhancement of the inhibitory system.
Mice ; Animals ; Receptor, trkB/metabolism* ; Neurons/metabolism* ; Signal Transduction

OBJECTIVETo study the regulation of anoikis by tyrosine kinase receptor B (TrkB) in human nasopharyngeal carcinoma lines. METHODS; Expression levels of TrkB and brain-derived neurotrophic factor (BDNF) were evaluated by RT-PCR and Western blot. Colony formation ability of C666-1 was observed in soft agar. Proliferation rate and apoptosis, that change in cells by treating the TrkB inhibitor K252a and specificity ligand BDNF respectively under suspension culture, were measured by cell counting kit-8 (CCK-8) assay and the flow cytometry assay. The expression change of TrkB, BDNF and phosphorylation of serine threonine kinase (p-Akt) were investigated by Western blot analysis.

RESULTSTrkB and BDNF were identified in C666-1 cells. C666-1 cells could be decreased the proliferation of colony in soft agar by effect of K252a, but BDNF could make the colony prolific. K252a can inhibit the expression of TrkB in C666-1, and prevent p-Akt activation. And exogenous BDNF stimulated up-regulation TrkB and p-Akt, induced anoikis resistance.

CONCLUSIONTrkB inhibits anoikis in nasopharyngeal carcinoma cells. Inhibiton of TrkB by K252a can induce anoikis, and may prove particularly effective in treatment of nasopharyngeal carcinoma.

Anoikis ; Carcinoma ; Cell Line, Tumor ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Receptor, trkB ; metabolism

OBJECTIVE: To investigate the roles of BDNF/TrkB neurotrophic signaling in hippocampal injury for fatigue rats induced by incremental load exercise and the protective effects and mechanism of spirulina supplement. METHODS: Sixty SD rats were randomly divided into normal control group (NC), normal plus spirulina group(NS), exercise model group (EM), exercise plus spirulina group (ES), and positive control group (PC), 12 rats in each group.Group EM, Group ES and Group PC were applied by treadmill running with high-intensity increasing for three weeks, and Group NC had not any intervention measures.Group ES and Group NS were treated with spirulina at a dose of 300 mg/kg.bw.by intragastric administration.Group PC was gavaged at the same volume of ginseng extract of 1.92 g/kg for three weeks.The expressions of brain-derived neurotrophic factor (BDNF), tyrosine kinase recptor (TrkB), phospho-tyrosine kinase recptor (p-TrkB) were tested by Western blot and immunohistochemical method, and micromorphology changes of hippocampal CA1 were observed by light microscope at the end of the experiment.The general situations of rats such as body weights were recorded during the experiment. RESULTS: Compared with Group NC, Group EM showed significantly decrease in body weight and hippocampal CA1 neurons of the group loosely arrayed and disarrayed and some neurons were shrinked, and even some neurons disappeared.The expressions of BDNF, TrkB and p-TrkB in group EM were increased significantly(<0.01).Compared with Group EM, body weight of Group ES was increased significantly, and the above mentioned injuries of neurons were improved significantly:the number of neurons and nissl bodies were significantly increased and the neurons arrayed regularly and its morphology was more complete.The expressions of BDNF, TrkB and p-TrkB in the group were increased significantly(<0.05 or <0.01).And there was no difference between Group ES and Group PC. CONCLUSIONS BDNF/TrkB neurotrophic signal pathway could be involved in the repair process of hippocampal nervous damage caused by incremental load exercise for fatigue rats.Spirulina supplement had a protective effect on the damaged nervous through increasing the expressions of BDNF, TrkB and p-TrkB.
Animals ; Brain-Derived Neurotrophic Factor ; Hippocampus ; Mice ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; Spirulina

OBJECTIVETo investigate the effects of high-affinity tyrosine kinase receptors TrkB, TrkC and the low-affinity neurotrophin receptor p75 in spiral ganglion cell (SGC) of cisplatin-induced ototoxicity.

METHODSThe 50 adult Wistar rats were divided randomly into 5 groups received intraperitoneal injection of cisplatin with vary dose. Control group was received equivalent volumes of saline. The group received 1 day intraperitoneal injection was cisplatin treated at a dose of 5 mg/kg and killed at next day. The group received 3 days was cisplatin treated for 3 days at same dose daily and then killed at next day. The group A received 5 days was cisplatin treated for 5 days and killed at next day. The group B received 5 days was cisplatin treated for 5 days and then were sacrificed after 7 days. The change of mRNA level of neurotrophin receptors in cochlear tissue were examined by RT-PCR. The expressing pattern of TrkB, TrkC, P75 in damaged cochlea were study by immunochemistry using antibodies against TrkB, TrkC, P75 protein.

RESULTSThe research data showed the expression of Trk B, Trk C, p75 exhibited in SGC was dynamic along with the administration lasting. The mRNA and protein level of Trk B (x(-) +/- s) at day 1 and 3 after cisplatin treatment were 0.76 +/- 0.06, 88.78 +/- 4.28, 0.82 +/- 0.09 and 91.64 +/- 4.06, with significant difference among those and other groups (P < 0.05). The mRNA and protein level of TrkC at day 1 after cisplatin treatment were 0.80 +/- 0.06 and 89.66 +/- 2.76, with significant difference among that and other groups (P < 0.05). The mRNA and protein level of p75 at the control group and cisplatin treated groups were 0.64 +/- 0.04, 55.16 +/- 3.10, 0.77 +/- 0.04, 78.46 +/- 3.86, 1.01 +/- 0.09, 105.02 +/- 6.61, 1.18 +/- 0.09, 111.10 +/- 6.08, 0.51 +/- 0.04 and 42.74 +/- 5.20, with significant difference among the control group and cisplatin treated groups (P < 0.05).

CONCLUSIONSThe expression of Trk B increased to peak at day 1 - 3 after cisplatin treatment and decreased at day 5 early and following weeks. The expression of Trk C went up to peak at day 1 after cisplatin treatment and went down during subsequently time. P75 kept a trend of continuance increased during the drug treatment and decrease at drug stopped. The expression of Trk B, Trk C and P75 may be involved in cochlear insult with cisplatin-induced. Trk B and Trk C may play an important role in the reparative process of cochlear, especially at early stage of the damage. P75 could promote SGC apoptosis in cisplatin-induced neurotoxicity.

Animals ; Cisplatin ; toxicity ; Male ; Rats ; Rats, Wistar ; Receptor, Nerve Growth Factor ; metabolism ; Receptor, trkB ; metabolism ; Receptor, trkC ; metabolism ; Spiral Ganglion ; drug effects ; metabolism

Brain-derived neurotrophic factor (BDNF) rapidly enhances synaptic transmission among the hippocampal neurons in the resting state. This mechanism may be due to the phosphorylation of NMDA receptors through its Trkb receptors on the postsynaptic neuron. In contrast, BDNF also has a suppressing effect on the synaptic transmission via non-NMDA receptors. The activities of non-NMDA receptors are known to modulate the NMDA receptors activities. This study was to investigate, using patch clamp technique, whether the BDNF increases or decreases the glutamate-induced synaptic transmission in which glutamate acts on both NMDA- and non-NMDA receptors. When a postsynaptic neuron was previously excited by a large amount of glutamate, BDNF decreased the synaptic transmission induced by subsequently-applied glutamate. However, when the signal entered into a postsynaptic neuron was blocked by the application of tetrodotoxin, BDNF increased the glutamate-induced responses. These results show that BDNF plays a role in a protection of the neurons against hazardous or uncontrolled activation of glutamate receptors and in an accentuation of the synaptic response when the signal is inevitably diminished.
Brain-Derived Neurotrophic Factor* ; Glutamic Acid ; Neurons* ; Phosphorylation ; Receptor, trkB ; Receptors, Glutamate ; Receptors, N-Methyl-D-Aspartate ; Synaptic Transmission* ; Tetrodotoxin

OBJECTIVE: To investigate the inhibitory effect of ANA-12 that blocks brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) signaling on inflammatory pain in rats and explore the underlying mechanism. METHODS: Forty-two adult SD rats were randomized into BDNF-induced acute pain group (n=24) and CFA-induced chronic pain group. The former group were randomly divided into 4 subgroups, including a control group, ANA-12 treatment group, BDNF treatment group, and BDNF+ANA-12 treatment group; the latter group were subgrouped into control group, CFA treatment group (CFA) and CFA + ANA-12 treatment group. The effects of ANA-12 treatment on pain behaviors of the rats with BDNF-induced acute pain and CFA-induced chronic inflammatory pain were observed. Western blotting was used to examine TrkB signaling and expressions of microglia marker protein Iba1 and TNF-α in the spinal cord of the rats. RESULTS: BDNF injection into the subarachnoid space significantly increased the number of spontaneous paw withdrawal of the rats (P < 0.05), which was obviously reduced by ANA-12 treatment (P < 0.05). The rats with intraplantar injection of CFA, showed significantly increased ipsilateral mechanical stimulation sensitivity (P < 0.05), and ANA-12 treatment obviously increased the ipsilateral foot withdrawal threshold (P < 0.05). Treatment with either BDNF or CFA significantly increased the phosphorylation level of TrkB (Y705) in the spinal cord of the rats (P < 0.05), which was significantly lowered by ANA-12 treatment (P < 0.05). Treatment with BDNF and CFA both significantly up-regulated the expressions of Iba1 and TNF-α in the spinal cord (P < 0.05), but ANA-12 significantly reduced their expression levels (P < 0.05). CONCLUSION ANA-12 can reduce spinal cord inflammation and relieve acute and chronic pain in rats by targeted blocking of BDNF/TrkB signaling.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Chronic Pain/drug therapy* ; Inflammation ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB/metabolism*

OBJECTIVETo observe the effects of acute immobilization stress on the mRNA expression of tyrosine kinase B (TrkB) in rats' hippocampus.

METHODSEighteen SD rats were randomly divided into three groups, i.e., the normal control group, the model group, and the medication group, 6 in each group. The acute immobilization stress model was prepared in the model group using acute immobilization for 2 h. Ginsenoside Rb1 (40 mg/kg) was peritoneally injected to rats in the medication group 30 min before modeling, with the same procedure as those for rats in the model group. No treatment was performed to rats in the normal control group. The plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) contents were detected using ELISA. The mRNA expression of TrkB in the rats' hippocampus was detected using real-time fluorescence quantitative RT-PCR.

RESULTSBefore modeling there was no statistical difference of plasma CORT or ACTH concentrations among three groups (P >0.05). The plasma CORT and ACTH concentrations increased in the model group and the medication group more significantly after modeling than before modeling, showing statistical difference (P <0.05). Besides, they were obviously higher in the model group than in the normal control group (P <0.05). They were obviously higher in the medication group than in the model control group (P <0.05). Compared with the normal control group, the mRNA expression of TrkB significantly decreased in the model group (87.73 +/- 7.62 vs 50.65 +/- 5.19, P < 0.05), showing statistical difference. The mRNA expression of TrkB was significantly higher in the medication group (78.91 +/- 18.07) than in the model group, showing statistical difference (P <0.05).

CONCLUSIONPretreatment by ginsenoside Rb1 could increase the plasma CORT and ACTH concentrations, maintain the mRNA expression of TrkB, thus relieving injury induced by acute immobilization stress.

Adrenocorticotropic Hormone ; blood ; Animals ; Corticosterone ; blood ; Ginsenosides ; pharmacology ; Hippocampus ; metabolism ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; genetics ; metabolism ; Stress, Psychological ; metabolism

OBJECTIVETo observe the effects of Shuyu Ningxin Recipe (SNR) on the praxiology and the expressions of hippocampal brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) of model rats with chronic stress-induced depression, thus exploring its anti-depression mechanisms.

METHODSSixty adult SD rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the fluoxetine group, the high dose SNR group, the medium dose SNR group, and the low dose SNR group, 10 in each group. All rats were subjected to establish chronic stress-induced depression model for 21 consecutive days. Except those in the normal control group, rats in the rest groups received gastrogavage from the 22nd day. Mice in the model group were administered with normal saline by gastrogavage. SNR at 25.0, 7.5, and 2.5 g/kg was respectively administered to rats in the high dose SNR group, the medium dose SNR group, and the low dose SNR group by gastrogavage. Fluoxetine suspension (12 mg/kg) was given to rats in the fluoxetine group by gastro-gavage. All medication lasted for 3 successive weeks. The weight, open-field test, and the immobility time in forced swimming test were determined before modeling, 3 weeks (after successful modeling), and 6 weeks (by the end of medication). The expressions of hippocampal BDNF and TrkB were measured after the brain tissues were drawn by the end of the experiment.

RESULTSCompared with the normal control group, the body weight grew slowly, the behavior index decreased, the immobility time in forced swimming test was prolonged, and the expressions of BDNF and TrkB were weaken in the model group (P <0.05, P <0.01).The body weight increased, the behavior was improved, the immobility time in forced swimming test was shortened, and the expressions of BDNF and TrkB were enhanced in the high dose SNR group and the fluoxetine group by the and of medication, showing statistical difference when compared with the model group (P <0.05, P <0.01).

CONCLUSIONSNR could exert anti-depression by improving the expression levels of hippocampal BDNF and TrkB.

Animals ; Behavior, Animal ; Brain-Derived Neurotrophic Factor ; metabolism ; Depression ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; metabolism ; Stress, Psychological ; metabolism

OBJECTIVETo study the effect of early environment on the learning-memory ability of rats and the expression of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), and to explore the influence of early environment on development of rat brain in developing stage and possible regulation mechanisms.

METHODSForty-five newborn Sprague-Dawley rats were randomly divided into three groups (15 rats in each group): enriched environment group (EE group), isolated environment group (IE group) and normal control group (NC group). The pups were nurtured separately in their groups. The learning-memory abilities of the rats were measured by "Y"-arm maze test 28 to 29 days after birth. The number of neural cells and the expression of BDNF and TrkB in the hippocampal CA3 and frontal lobe were were detected by Nissl's staining and immunohistochemistry respectively.

RESULTSThe results of the "Y"-arm maze test showed that rats in the EE group needed less training times, and retained a higher percentage of memory than the other two groups(P<0.01). Rats in the IE group needed more training times, and retained a lower percentage of memory than the NC group (P<0.01). By Nissl's staining, the numbers of neural cells in the hippocampal CA3 and frontal lobe were highest in the EE group followed by the NC group. They were lowest in the IE group (P<0.01). By immunohistochemistry, the expression of BDNF in the hippocampal CA3 and frontal lobe were highest in the EE group followed by the NC group. It was lowest in the IE group (P<0.01). Results were similar for expression of TrkB.

CONCLUSIONSEarly environment can affect the long-term brain development and brain function of rats by influencing the expression of BDNF and its receptor TrkB in the hippocampus and frontal lobe.

Animals ; Body Weight ; Brain ; growth & development ; Brain-Derived Neurotrophic Factor ; analysis ; Female ; Hippocampus ; chemistry ; pathology ; Male ; Maze Learning ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; analysis ; Social Isolation

OBJECTIVETo study the influence of multiple myeloma cells on normal endothelial cells in co-culture system.

METHODSHuman multiple myeloma cell line RPMI8226 was co-cultured with human umbilical vein endothelial cells (HUVECs). HUVECs cultured alone were used as control. The expression of brain derived neurotrophic factor (BDNF) and its specific acceptor TrkB mRNA and protein in HUVECs were determined by RT-PCR and Western blot, respectively, BDNF levels in culture supernatant by enzyme-linked immunosorbent assay (ELISA). After transferring the co-culture, the effects RPMI8226 on HUVECs angiogenesis were studied by modified transwell migration assay and net-like formation assay.

RESULTSThe median BDNF concentration in culture supernatant was increased in co-cultured HUVECs compared with that in HUVECs cultured alone [(31.6 +/- 7.2) ng/ml vs (12.4 +/- 5.1) ng/ml, P < 0.05]. The expression of BDNF transcript demonstrated by RT-PCR did the same in the two culture systems (1.7 fold increase, P < 0.05). TrkB mRNA was hardly detected in culture of HUVECs alone but was increased in co-cultured HUVECs (4.4- fold increase, P < 0.05). The BDNF and TrkB protein expressions determined by Western blot were similar to that of their mRNAs. On the other hand, the RPMI8226 activated HUVECs showed enhanced migration and net-like formation, being increased by 99% and 72% , respectively. Addition of anti-human BDNF antibody to the culture medium partly reduced these effects.

CONCLUSIONMultiple myeloma cells activated BDNF/TrkB autocrine loops in co-cultured endothelial cells and resulted in endothelial self-activating angiogenesis.

Brain-Derived Neurotrophic Factor ; metabolism ; Cell Communication ; Cell Line, Tumor ; Coculture Techniques ; Endothelial Cells ; cytology ; metabolism ; Humans ; Multiple Myeloma ; pathology ; Neovascularization, Physiologic ; RNA, Messenger ; metabolism ; Receptor, trkB ; metabolism