Objective:Based on the BDNF/TrkB/CREB pathway,to explore the mechanism of neuronal apoptosis and brain developmental injury in the hippocampus of hypoxic-ischemic neonatal rats.Methods:Wistar young rats were ligated o...Objective:Based on the BDNF/TrkB/CREB pathway,to explore the mechanism of neuronal apoptosis and brain developmental injury in the hippocampus of hypoxic-ischemic neonatal rats.Methods:Wistar young rats were ligated on one side of the common carotid artery and placed in an 8%oxygen and 92%nitrogen hypoxia box for 2 h to prepare hypoxic-ischemic brain injury models.Healthy rats were used as the control group.Control group and model group were selected,with 10 rats in each group,and the learning and memory ability was tested by Y-maze;2,3,5-triphenyltetrazolium chloride(TTC)staining was used to detect brain tissue damage;Western blot was performed to determine the expression of brain-derived neurotrophic factor(BDNF),tyrosine protein kinase B(TrKB)and cAMP-response element binding protein(CREB)in hippocampal tissue.Another 15 mice in the control group and 60 mice in the model group were divided into negative control group(NC),BDNF overexpression group(LV-BDNF),TrkB overexpression group(LV-TrkB),and CREB overexpression group(LV-CREB),blank vector,BDNF,TrkB,CREB adenovirus overexpression vector was injected into the tail vein.Y-maze test for learning and memory ability;TTC staining method to detect brain tissue damage;neuronal apoptosis in the hippocampus were detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling;Western blot to detect the level of neuronal apoptosis in the hippocampus.Apoptosis-related protein B-cell lymphoma-2(Bcl-2),BCL2associated X protein(Bcl-2 Assaciated X,Bax)and nuclear factor kappaB(NFκB)expression.Results:The learning and memory ability of the young mice in the model group was significantly reduced,the brain infarct volume was significantly increased,the expressions of BDNF and TrkB proteins in the hippocampus were significantly increased,and the expression of CREB proteins was significantly decreased;After overexpression of BDNF and TrkB CREB,in the LVBDNF,LVTrkB,and LVCREB group,the learning and memory ability of young mice were significantly improved,the brain infarct volume were significantly reduced,the hippocampal neuronal apoptosis were significantly reduced,The protein expression of Bax and NFκB were significantly decreased and the protein expression of Bcl2 were significantly enhanced.Conclusion:The expression of BDNF/TrkB/CREB is abnormal in HIBI model young mice.Overexpression of BDNF/TrkB/CREB can improve the learning and memory ability of young mice,repair brain tissue damage,and inhibit neuronal apoptosis.Therefore,the mechanism of HIBI may be related to BDNF/TrkB/CREB pathways.展开更多
Objective:To investigate the effect of electroacupuncture on CREB/BDNF/TrkB signaling pathway in hippocampus of depressed rats.Methods:The depression rat model was established by chronic unpredictable stress(CUMS)comb...Objective:To investigate the effect of electroacupuncture on CREB/BDNF/TrkB signaling pathway in hippocampus of depressed rats.Methods:The depression rat model was established by chronic unpredictable stress(CUMS)combined with solitary rearing.The rats were randomly divided into blank group,model group,electroacupuncture group and fluoxetine group,with 10 rats in each group.In the electroacupuncture group,‘Baihui',‘Shenting',‘Hegu'and‘Taichong'were selected.Acupuncture was performed 1 h before modeling every day,and the needles were retained for 20 min,once a day for 21 d.Fluoxetine group:Fluoxetine(10 mg/kg,1 mg/mL)was intragastrically administered 1 h before modeling for 21 d.The changes of body weight,the number of standing and the distance of movement in open field test,the immobility time of forced swimming test were observed.The contents of 5-HT,DA and NE in serum were detected by ELISA.The expression of BDNF,CREB and TrkB in hippocampus was detected by Western blot.The expression of BDNF and CREB mRNA in hippocampus was detected by real-time fluorescence quantitative PCR.Results:After modeling intervention:Compared with the blank group,the body weight,the number of standing,the distance of movement,the content of serum 5-HT,DA and NE,the expression of BDNF,CREB and TrkB in the hippocampus of the model group were significantly decreased(all P<0.01),and the immobility time was significantly increased(P<0.01).Compared with the model group,the body weight,the number of standing,the distance of movement,the content of 5-HT,DA and NE in serum,the expression of BDNF,CREB and TrkB in hippocampus were significantly increased(all P<0.05),and the immobility time was significantly decreased(P<0.05)in the EA group and fluoxetine group.There was no significant difference between the electroacupuncture group and the fluoxetine group(P>0.05).Conclusion:EA can significantly improve the symptoms of depression in rats,and its mechanism may be related to the regulation of BDNF/TrkB/CREB signaling pathway-related proteins in hippocampus,increase the content of monoamine neurotransmitters 5-HT,NE and DA,resulting in antidepressant effect.展开更多
[Objectives] To investigate the effects of ginseng protein on gut microbiota and BDNF/TrkB signaling pathway in Alzheimer s disease (AD) mice. [Methods] D-galactose/AlCl 3 co-induction was used to establish AD model, ...[Objectives] To investigate the effects of ginseng protein on gut microbiota and BDNF/TrkB signaling pathway in Alzheimer s disease (AD) mice. [Methods] D-galactose/AlCl 3 co-induction was used to establish AD model, and mice were randomly divided into normal group 1, normal group 2, model group 1, model group 2, ginseng protein group, and microbiota transplantation group. Morris water maze experiment was used to evaluate learning and memory ability, and Western blot method was used to detect the expression of APP, p-Tau, BDNF, TrkB, p-TrkB proteins in brain tissue, and 16S rDNA was used to detect diversity of fecal microbiota. [Results] Ginseng protein and microbiota transplantation can shorten the escape latency of mice ( P <0.05), increase the number of crossing platforms ( P <0.05), reduce the expression of APP and p-Tau proteins in brain tissue ( P <0.05, P <0.01), increase the expression of BDNF, p-TrkB, p-TrkB/TrkB proteins ( P <0.05, P <0.01), and reduce the abundance of Alloprevotella, Ruminococcaceae _UCG-014, Prevotellaceae _UCG-001, and Ruminococcus _1 ( P <0.05, P <0.01). [Conclusions] The action mechanism of ginseng protein anti AD may be through regulating gut microbiota diversity and activating the BDNF/TrkB signaling pathway.展开更多
This study was to determine the protective effect of ω-3 polyunsaturated fatty acids（ω-3PUFAs） on MK-801-induced cognitive impairment in schizophrenia（SZ） rats and the underlying mechanism. A rat model of schizo...This study was to determine the protective effect of ω-3 polyunsaturated fatty acids（ω-3PUFAs） on MK-801-induced cognitive impairment in schizophrenia（SZ） rats and the underlying mechanism. A rat model of schizophrenia was induced by MK-801. The cognitive function of rats was assessed using a Morris water maze. The number of hippocampal neurons was measured by Nissl staining. The expression of CREB, p-CREB, BDNF, TrkB, p-TrkB, AKT, p-AKT, ERK, and p-ERK in the hippocampus of rats was detected by Western blotting. The results showed that ω-3PUFAs attenuated MK-801-induced cognitive impairment and hippocampal neurons loss, reversed the injury of the CREB/BDNF/TrkB pathway induced by MK-801, and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats. In conclusion, ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT, thereby increasing the synaptic plasticity and decreasing neuron loss, and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.展开更多
Objective:To observe the effect of Anshen Dingzhi Decoction on tau phosphorylation in hippocampus of Alzheimer's disease rat model and its related mechanism.Methods:SD rats were randomly divided into control group...Objective:To observe the effect of Anshen Dingzhi Decoction on tau phosphorylation in hippocampus of Alzheimer's disease rat model and its related mechanism.Methods:SD rats were randomly divided into control group,model group,Anshen Dingzhi Decoction(low,medium and high dose group)and Dopazide group.Except for the control group,the rats in the other groups were injected with streptozotocin into the lateral ventricle to replicate the model of Alzheimer's disease and then given corresponding drugs for 2 weeks.orris water maze test was used to detect learning and memory ability of rats,HE staining was used to detect hippocampal histological morphology,Western-blot was used to detect tau phosphorylation level and expression abundance of BDNF and TrkB protein in hippocampal tissue of rats.Results:The escape latency of the model group was significantly increased,the number of crossing platforms and effective residence time were significantly reduced,the phosphorylation level of tau protein was significantly increased,and the phosphorylation levels of BDNF and TrkB protein were significantly decreased when compared with the control group,the difference has statistically significant(P<0.05).Anshen Dingzhi Fang could significantly reduce the escape latency of AD rats,increase the number of crossing platforms and effective residence time,inhibit the phosphorylation of tau protein,and up-regulate the phosphorylation of BDNF and TrkB protein,the difference was statistically significant when compared with the model group(P<0.05).Conclusion:Anshen Dingzhi Fang can inhibit the phosphorylation of tau protein by activating BDNF/TrkB signaling pathway and promote the learning and memory ability of AD rats.展开更多
基金Hainan Provincial Natural Science Foundation of China(NO.819QN388)。
文摘Objective:Based on the BDNF/TrkB/CREB pathway,to explore the mechanism of neuronal apoptosis and brain developmental injury in the hippocampus of hypoxic-ischemic neonatal rats.Methods:Wistar young rats were ligated on one side of the common carotid artery and placed in an 8%oxygen and 92%nitrogen hypoxia box for 2 h to prepare hypoxic-ischemic brain injury models.Healthy rats were used as the control group.Control group and model group were selected,with 10 rats in each group,and the learning and memory ability was tested by Y-maze;2,3,5-triphenyltetrazolium chloride(TTC)staining was used to detect brain tissue damage;Western blot was performed to determine the expression of brain-derived neurotrophic factor(BDNF),tyrosine protein kinase B(TrKB)and cAMP-response element binding protein(CREB)in hippocampal tissue.Another 15 mice in the control group and 60 mice in the model group were divided into negative control group(NC),BDNF overexpression group(LV-BDNF),TrkB overexpression group(LV-TrkB),and CREB overexpression group(LV-CREB),blank vector,BDNF,TrkB,CREB adenovirus overexpression vector was injected into the tail vein.Y-maze test for learning and memory ability;TTC staining method to detect brain tissue damage;neuronal apoptosis in the hippocampus were detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling;Western blot to detect the level of neuronal apoptosis in the hippocampus.Apoptosis-related protein B-cell lymphoma-2(Bcl-2),BCL2associated X protein(Bcl-2 Assaciated X,Bax)and nuclear factor kappaB(NFκB)expression.Results:The learning and memory ability of the young mice in the model group was significantly reduced,the brain infarct volume was significantly increased,the expressions of BDNF and TrkB proteins in the hippocampus were significantly increased,and the expression of CREB proteins was significantly decreased;After overexpression of BDNF and TrkB CREB,in the LVBDNF,LVTrkB,and LVCREB group,the learning and memory ability of young mice were significantly improved,the brain infarct volume were significantly reduced,the hippocampal neuronal apoptosis were significantly reduced,The protein expression of Bax and NFκB were significantly decreased and the protein expression of Bcl2 were significantly enhanced.Conclusion:The expression of BDNF/TrkB/CREB is abnormal in HIBI model young mice.Overexpression of BDNF/TrkB/CREB can improve the learning and memory ability of young mice,repair brain tissue damage,and inhibit neuronal apoptosis.Therefore,the mechanism of HIBI may be related to BDNF/TrkB/CREB pathways.
基金supported by Scientific Research Project of Traditional Chinese Medicine Administration of Shanxi Province(2019ZYYC036)。
文摘Objective:To investigate the effect of electroacupuncture on CREB/BDNF/TrkB signaling pathway in hippocampus of depressed rats.Methods:The depression rat model was established by chronic unpredictable stress(CUMS)combined with solitary rearing.The rats were randomly divided into blank group,model group,electroacupuncture group and fluoxetine group,with 10 rats in each group.In the electroacupuncture group,‘Baihui',‘Shenting',‘Hegu'and‘Taichong'were selected.Acupuncture was performed 1 h before modeling every day,and the needles were retained for 20 min,once a day for 21 d.Fluoxetine group:Fluoxetine(10 mg/kg,1 mg/mL)was intragastrically administered 1 h before modeling for 21 d.The changes of body weight,the number of standing and the distance of movement in open field test,the immobility time of forced swimming test were observed.The contents of 5-HT,DA and NE in serum were detected by ELISA.The expression of BDNF,CREB and TrkB in hippocampus was detected by Western blot.The expression of BDNF and CREB mRNA in hippocampus was detected by real-time fluorescence quantitative PCR.Results:After modeling intervention:Compared with the blank group,the body weight,the number of standing,the distance of movement,the content of serum 5-HT,DA and NE,the expression of BDNF,CREB and TrkB in the hippocampus of the model group were significantly decreased(all P<0.01),and the immobility time was significantly increased(P<0.01).Compared with the model group,the body weight,the number of standing,the distance of movement,the content of 5-HT,DA and NE in serum,the expression of BDNF,CREB and TrkB in hippocampus were significantly increased(all P<0.05),and the immobility time was significantly decreased(P<0.05)in the EA group and fluoxetine group.There was no significant difference between the electroacupuncture group and the fluoxetine group(P>0.05).Conclusion:EA can significantly improve the symptoms of depression in rats,and its mechanism may be related to the regulation of BDNF/TrkB/CREB signaling pathway-related proteins in hippocampus,increase the content of monoamine neurotransmitters 5-HT,NE and DA,resulting in antidepressant effect.
基金Supported by Liaoning Province Science and Technology Department Project(20180530033,2022-MS-281)Liaoning Provincial Department of Education Project(LJKZZ20220105)Liaoning University of Traditional Chinese Medicine Project(2021LZY042).
文摘[Objectives] To investigate the effects of ginseng protein on gut microbiota and BDNF/TrkB signaling pathway in Alzheimer s disease (AD) mice. [Methods] D-galactose/AlCl 3 co-induction was used to establish AD model, and mice were randomly divided into normal group 1, normal group 2, model group 1, model group 2, ginseng protein group, and microbiota transplantation group. Morris water maze experiment was used to evaluate learning and memory ability, and Western blot method was used to detect the expression of APP, p-Tau, BDNF, TrkB, p-TrkB proteins in brain tissue, and 16S rDNA was used to detect diversity of fecal microbiota. [Results] Ginseng protein and microbiota transplantation can shorten the escape latency of mice ( P <0.05), increase the number of crossing platforms ( P <0.05), reduce the expression of APP and p-Tau proteins in brain tissue ( P <0.05, P <0.01), increase the expression of BDNF, p-TrkB, p-TrkB/TrkB proteins ( P <0.05, P <0.01), and reduce the abundance of Alloprevotella, Ruminococcaceae _UCG-014, Prevotellaceae _UCG-001, and Ruminococcus _1 ( P <0.05, P <0.01). [Conclusions] The action mechanism of ginseng protein anti AD may be through regulating gut microbiota diversity and activating the BDNF/TrkB signaling pathway.
基金supported in parts by grants from the Hubei Province Key Technology R&D Program(No.2015BCE094)Wuhan Science and Technology Bureau Dawn Plan Project(No.201507040410216)+1 种基金Clinical Research Physician Program of Tongji Medical CollegeHUST and the Academic Frontier Youth Team Project of HUST
文摘This study was to determine the protective effect of ω-3 polyunsaturated fatty acids（ω-3PUFAs） on MK-801-induced cognitive impairment in schizophrenia（SZ） rats and the underlying mechanism. A rat model of schizophrenia was induced by MK-801. The cognitive function of rats was assessed using a Morris water maze. The number of hippocampal neurons was measured by Nissl staining. The expression of CREB, p-CREB, BDNF, TrkB, p-TrkB, AKT, p-AKT, ERK, and p-ERK in the hippocampus of rats was detected by Western blotting. The results showed that ω-3PUFAs attenuated MK-801-induced cognitive impairment and hippocampal neurons loss, reversed the injury of the CREB/BDNF/TrkB pathway induced by MK-801, and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats. In conclusion, ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT, thereby increasing the synaptic plasticity and decreasing neuron loss, and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.
基金Natural science fund of Heilongjiang province(No.H2018063).
文摘Objective:To observe the effect of Anshen Dingzhi Decoction on tau phosphorylation in hippocampus of Alzheimer's disease rat model and its related mechanism.Methods:SD rats were randomly divided into control group,model group,Anshen Dingzhi Decoction(low,medium and high dose group)and Dopazide group.Except for the control group,the rats in the other groups were injected with streptozotocin into the lateral ventricle to replicate the model of Alzheimer's disease and then given corresponding drugs for 2 weeks.orris water maze test was used to detect learning and memory ability of rats,HE staining was used to detect hippocampal histological morphology,Western-blot was used to detect tau phosphorylation level and expression abundance of BDNF and TrkB protein in hippocampal tissue of rats.Results:The escape latency of the model group was significantly increased,the number of crossing platforms and effective residence time were significantly reduced,the phosphorylation level of tau protein was significantly increased,and the phosphorylation levels of BDNF and TrkB protein were significantly decreased when compared with the control group,the difference has statistically significant(P<0.05).Anshen Dingzhi Fang could significantly reduce the escape latency of AD rats,increase the number of crossing platforms and effective residence time,inhibit the phosphorylation of tau protein,and up-regulate the phosphorylation of BDNF and TrkB protein,the difference was statistically significant when compared with the model group(P<0.05).Conclusion:Anshen Dingzhi Fang can inhibit the phosphorylation of tau protein by activating BDNF/TrkB signaling pathway and promote the learning and memory ability of AD rats.
