Effect of electrical stimulation at auricular points combined with sound masking on the expression of CREB, BDNF and TrkB in the auditory cortex of tinnitus rats / 中国针灸

OBJECTIVE@#To explore the effect of electrical stimulation at auricular points (EAS) combined with sound masking on the expression of cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in the auditory cortex of tinnitus rats.@*METHODS@#A total of 27 adult male SD rats were randomly divided into a control group, a model group and an EAS group. The rats in the model group and the EAS group were intervened with intraperitoneal injection of sodium salicylate to induce tinnitus model, while the rats in the control group were intervened with injection of 0.9% NaCl solution. After the model was successfully established, the rats in the EAS group were treated with electrical stimulation at "Shenmen" (TF) and "Yidan" (CO), combined with sound masking; the treatment was given once a day for 15 days. The gap prepulse inhibition of acoustic startle (GPIAS) and prepulse inhibition (PPI) testing were performed using the acoustic startle reflex starter package for rats. The expression of BDNF, TrkB, CREB and p-CREB in the auditory cortex of each group were measured with Western Blot analysis.@*RESULTS@#① Compared with the control group, the GPIAS values in 12 kHz, 16 kHz, 20 kHz and 28 kHz were significantly decreased in the model group (all 0.05).@*CONCLUSION@#EAS could improve the GPIAS values of high-frequency background sound in tinnitus rats, which may be related with the upregulation of the BDNF/TrkB/CREB signaling pathway in the auditory cortex, leading to the reversion of the maladaptive plasticity.

Antidepressant activity of flavonoid ethanol extract of Abelmoschus manihot corolla with BDNF up-regulation in the hippocampus / 药学学报

Abelmoschus manihot (L.) Medic., a folk herbal medicine in China, is a flowering plant belonging to Abelmoschus L. genus and Malvaceae family, which has been reported with an antidepressant activity. The study was designed to isolate flavonoids from Abelmoschus manihot corolla and explore the action mechanism of antidepressant activities. The flavonoids were isolated and purified by D101 macroporous resin column, polyamide column and Sephadex LH-20 sequentially and identified as myricetin-3-O-β-D-glucoside (1), gossypetin-8-O-β-D-glucuronide (2, G-8-G), gossypetin-3'-O-β-D-glucoside (3), quercetin-3'-glucoside (4, Q-3-G), isoquercitrin (5, IQT), hyperoside (6, HY), myricetin (7), quercetin (8, QT). Compounds 2, 4, 5, 6 and 8 (15, 30 and 60 mg·kg-1) were orally administered to mice and the reaction was observed in tail suspension test (TST) and forced swimming test (FST). Western blot analysis was used in determination of the protein expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB) and phosphorylation eukaryotic elongation factor 2 (p-eEF2). The results revealed that only Q-3-G and G-8-G (15, 30, 60 mg·kg-1) significantly reduced the immobility time in FST and TST. Furthermore, Q-3-G and G-8-G remarkably increased the expression of BDNF and TrkB, and decreased the expression of p-eEF2. These results suggest that Q-3-G and G-8-G had an obvious antidepressant activity via up-regulation of BDNF expression. The new observation will provide a new direction in the development of antidepressant in the treatment of major depressive disorder (MDD).

Role of BDNF-trkB signaling pathway in ketamine treating diabetic neuropathic pain / 中国药理学通报

Aim Toinvestigatetheroleofbrain-de-rived neurotrophic factor(BDNF)-tyrosine receptor ki-nase B (trkB ) signaling pathway in the therapeutic effects of ketamine on diabetic neuropathic pain.Meth-ods Forty-eightWistarrats,aged3months,weighing 200~250 g,were equally randomized into 4 groups(n=12 ):control group (C group ), saline group (S group),ketamine group (K group)and ketamine +ANA-12 group (KA group ).Rats in S,K and KA groups were intraperitoneally injected with a single of streptozotocin(STZ)65 mg·kg-1 to construct diabetic neuropathic pain model.After twenty-eight days,rats in S,K and KA groups were intraperitoneally injected with saline, ketamine 10 mg·kg-1 and ketamine 10 mg·kg-1 +ANA-12 0. 5 mg·kg-1 for consecutive 7 days, respectively. On the 8th day, mechanical withdrawal threshold(MWT)of rats was measured.Af-ter that,the rats were immediately sacrificed,and dor-sal ganglion of lumbar spine and prefrontal cortex (PFC)were harvested for measuring BDNF,p-trkB/trkB,synaptophysin and spine density by Western blot andglogistaining.Results ComparedwithCgroup, rats in S group significantly decreased MWT,BDNF, p-trkB/trkB,synaptophysin and spine density in dorsal ganglion and PFC (P <0. 05 ).Compared with S group,rats in K group showed a significant increase of MWT,BDNF,p-trkB/trkB,synaptophysin and spine density in the all observed regions(P<0. 05 ).On the contrary,rats in KA group showed a significant de-crease of MWT and BDNF,p-trkB/trkB,synaptophys-in and spine density as compared with K group in all regions(P<0. 05 ).Furthermore,BDNF was positive-ly correlated with spine density in all regions (P <0.05).Conclusion BDNF-trkBsignalingpathway mediates ketamine-induced therapeutic effects in dia-betic neuropathic pain.

Protective effect of BNDF on vascular endothelial cells with H2 O2-induced oxidative injury / 中国病理生理杂志

[ABSTRACT]AIM:Tostudytheprotectiveeffectofbrain-derivedneurotrophicfactor(BDNF)onvascularendo-thelial cells with H 2 O2-induced oxidative injury .METHODS: Human umbilical vein endothelial cells ( HUVECs ) were cultured in vitro, and the oxidation injury model of HUVECs was established by treatment with H 2 O2 .The oxidatively in-jured HUVECs were cultured with different concentrations (1, 10 and 100μg/L) of BDNF.At the same time, the control group (no injury), PBS treatment after H2O2 injury group and TrkB inhibitor group (with 100 μg/L BDNF and 1∶1 000 TrkB inhibitor) were also set up.The viability of the HUVECs was detected by MTT assay .The levels of LDH, MDA, SOD and GSH were measured .The releases of NO , ET-1 and ICAM-1 were analyzed by ELISA .The changes of ROS pro-duction and cell apoptosis were evaluated by flow cytometry .The protein levels of TrkB , p-TrkB, cleaved caspase-3, Bcl-2 and Bax were determined by Western blot .RESULTS:Compared with uninjured control group , in H2 O2 oxidative injury plus PBS treatment group , the viability of the cells was decreased significantly , the LDH and MDA levels were increased significantly and the activities of SOD and GSH were decreased significantly .The NO secretion was decreased , and the ET-1 and ICAM-1 concentrations were increased significantly .The ROS content and apoptotic rate were increased significantly . The protein levels of cleaved caspase-3 and Bax were increased but Bcl-2 protein expression was decreased significantly . Compared with PBS treatment group , in H2 O2-injured HUVECs treated with different concentrations of BDNF , the cell via-bility was gradually increased , the LDH and MDA levels were decreased and the activities of SOD and GSH were increased gradually .The secretion of NO was increased but ET-1 and ICAM-1 were decreased gradually .The ROS content and apop-totic rate were decreased significantly .The TrkB and p-TrkB levels were significantly increased significantly , the protein expression of cleaved-caspase 3 and Bax was decreased gradually and the Bcl-2 protein expression increased gradually .The role of BDNF was inhibited by TrkB inhibitor .CONCLUSION:BDNF protects HUVECs from oxidative injury by binding with TrkB to activate the BDNF-TrkB signaling pathways .

Recent approach of brain-derived neurotrophic factor and signal transduction pathways in hypoxic ischemic brain damage / 国际儿科学杂志

Brain-derived neurotrophic factor(BDNF)belongs to the neurotrophin family and abundantly expressed in the nervous system.It plays an essential role in the survival,development,function,morphogenesis and plasticity of neurons by binding to the tyresine receptor kinase B(TrkB)and subsequent downstream activation of several signal transduction pathways in the nervous system. The PI3K/Akt and the MAPK/ERK DathWays ale two major intracellular signaling network activated by BDNF involved in survival of neurons.Becently.it is investigated that BDNF and TrkB are involved in the pathophysiology of hypoxic ischemic brain damage (HIBD)and in the mechanism of action of therapeutic agents.Therefore we image changing the internal or external condIitions can increase the expression of BDNF,thsu reduce the nervous system damage of HIBD.