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

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 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

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

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

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

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

OBJECTIVE: This study was to explore the expression and clinicopathologic features of Tyrosine kinase receptors B (TrkB) and its ligand brain-derived neurotrophic factor (BDNF) in nasopharyngeal carcinoma (NPC). METHOD: Immunohistochemistry was adopted to detect the expression level of TrkB and BDNF in NPC patients. RESULT: Both TrkB and BDNF were expressed in NPC as well as in chronic inflammation. The active expression rate of TrkB in NPC was 82.5% (47/57) and BDNF was 52.6% (30/57), both of which were higher than those in chronic inflammation (P < 0.05). The degree of TrkB expression was more marked in T3 + T4, III + IV stage NPC than that in T1 +T2, I + II stage NPC (P < 0.05). TrkB abnormal expression rate of nasopharyngeal carcinoma with lymph node metastasis was higher than that of NPC without lymph node metastasis (P < 0.05). No statistical significance for degrees of TrkB expression in pathologic type grades was found (P > 0.05). There were no statistical significance for degrees of BDNF expression in T stage, clinical stage and lymph node metastasis in NPC (P > 0.05). The expression of TrkB was unrelated to the expression of BDNF (r = 0.049, P > 0.05). CONCLUSION The high expression rate of TrkB and BDNF maybe plays an important role in development of NPC. It is suggested that TrkB and its ligand BDNF may act as an important index for forecasting the development and metastasis of NPC.
Adolescent ; Adult ; Aged ; Brain-Derived Neurotrophic Factor ; metabolism ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Staging ; Receptor, trkB ; metabolism ; Young Adult

OBJECTIVETo study the effect o f Bushen Huoxue Decoction (BHD) on neurobiochemical markers in the hippocampus of female rats with repeated immobilization stress.

METHODSSixty female rats were randomly divided into the normal group, the model group, the positive control group (treated with Liuwei Dihuang Pill at the dose of 3.3 g crude drug/kg), and the high, middle, and low BHD treated groups (at the dose of 8, 4, 2 g crude drug/kg), ten in each group. Chronic psychological stress was induced using repeated immobilization stress in rats. Medication was conducted by gastrogavage while modeling once a day for twenty successive days. The hippocampal neurohumoral levels were detected with high-performance liquid chromatography. The expression levels of BDNF and its receptor in the hippocampus were detected by Westem blot. Effect of BHD on neurobiochemical markers in the hippocampus of rats with repeated immobilization stress was observed.

RESULTSThe levels of Glu, GABA, and BDNF in the hippocampus of the normal group were 1280.0 +/- 258.3 ng/mg, 588.3 +/- 115.1 ng/mg, and 13.26 +/- 2.57 gray value, respectively. But the hippocampal neurohumoral levels and the expression of BDNF in the model group obviously decreased when compared with the normal group, being 1016.9 +/- 215.9 ng/mg, 485.1 +/- 71.0 ng/mg, and 7.23 +/- 0.61 gray value, respectively. The levels of Glu (ng/mg) in hippocampus of the three BHD treated groups were 1459.1 +/- 413.5, 1894.7 +/- 542.8, and 1373.3 +/- 345.7, respectively. GABA levels (ng/mg) inthe hippocampus were 631.6 +/- 161.4, 899.1 +/- 262.1, and 656.4 +/- 140.8, respectively. BDNF levels (gray value) were 16.57 +/- 1.52, 29.85 +/- 1.37, and 24.44 +/- 3.81, respectively, significantly higher than that of the model group (P<0.05, P<0.01). The level of Glu in the positive control group (1216.5 +/- 193.8 ng/mg) was significantly higher than that of model group (P<0.05).

CONCLUSIONBHD showed significant accommodation on the hippocampal neurohumoral levels and the expression of BDNF in the female rats with repeated immobilization stress.

Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Glutamic Acid ; metabolism ; Hippocampus ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; metabolism ; Restraint, Physical ; Stress, Psychological ; metabolism ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo investigate the effects of Chaihu Shugan Powder (CHSGP) on the behavior and the expressions of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase receptors B (TrkB) in the hippocampus, amygdala, and the frontal lobe of depression model rats.

METHODSSixty adult Sprague-Dawley rats were randomly divided into 6 groups, i. e., the normal control group (NC), the model control group (MC), the CHSGP group, the disassembly 1 group (CI), the disassembly 2 group (CII), and the Fluoxetine control group (FC), 10 in each group. Except those in the NC, the rest rats were singly housed and exposed on an unpredicted sequence of mild stressor. From the fifteenth day, all rats were administered with equal volume of normal saline (to the NC group and the MC group) and of corresponding medicinal liquid (5.9 g/kg to the CHSGP group, 3.3 g/kg to the CI group, 2.6 g/kg to the CII group, and 1.8 mg/kg to the FC group) by gastrogavage for 2 successive weeks. The rats' body weight, sucrose consumption volume in the sucrose preference test, and times of grooming in the open field test were detected on the 0, 7th, 14th, 21st, 28th day, respectively. The mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe were detected by immunohistochemical assay and Real-time fluorescent quantitation PCR.

RESULTSCompared with the NC group, the rats' body weight was put up slowly in the MC group. The scores in the open field test decreased. The times of grooming and sucrose consumption volume were both reduced. The time of staying in central square was postponed. The mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe decreased with statistical significance (P<0.05, P<0.01). Compared with the MC group, the behavior indices of rats in the CHSGP, CI, CII, and FC groups were significantly improved. The mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe were obviously enhanced with statistical significance (P<0.05, P<0.01).

CONCLUSIONSCHSGP could obviously improve the depressive state of the model rats. Its mechanism might be correlated with increasing the mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe.

Amygdala ; metabolism ; Animals ; Behavior, Animal ; drug effects ; Brain-Derived Neurotrophic Factor ; metabolism ; Depression ; drug therapy ; metabolism ; Frontal Lobe ; metabolism ; Hippocampus ; metabolism ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; metabolism