The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical...The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical and non-canonical signaling mechanisms relevant to brain damage.We explore how ErbB signaling is dynamically regulated following injury and how it orchestrates processes such as neuroinflammation,gliosis,and neural repair.Special attention is given to its interplay with other critical pathways,including Notch signaling,and its roles within adult neurogenic niches,where it modulates neural stem cell behavior in response to damage.Based on accumulating preclinical evidence,we propose two therapeutic strategies for targeting ErbB signaling in brain injury:(1)dampening neuroinflammation through ErbB inhibition and(2)promoting neuroprotection and neurogenesis via neuregulin-1-mediated activation.The first strategy is supported by studies,which demonstrate that inhibition of ErbB1 limits neuroinflammation and supports neural repair in preclinical models.The latter strategy is supported by emerging studies demonstrating the significant potential of novel protein kinase C activating diterpenes in modulating ErbB signaling pathways through the regulation of neuregulin-1 release.Diterpenes,by influencing the ErbB pathway,may uniquely bridge the gap between neuroprotection and regeneration.Their potential to modulate inflammation and promote pro-regenerative cellular environments positions them as promising tools in the development of targeted therapies.By dissecting these mechanisms,we aim to shed light on the translational potential of ErbB-targeted therapies and their capacity to enhance endogenous repair processes in the injured brain.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
[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
Aging affects the nervous system as well as other organs.In our study,we aimed to study the pharmacological effects and mechanism of porcine placental peptides(PPP)in aging process,and to observe the changes of neurob...Aging affects the nervous system as well as other organs.In our study,we aimed to study the pharmacological effects and mechanism of porcine placental peptides(PPP)in aging process,and to observe the changes of neuroblast proliferation and differentiation as well as partial gene expression in hippocampus of D-galactose-induced aged mouse.Based on the analysis of experimental results,it was confirmed that PPP significantly improved neurobalst proliferation and differentiation in the mouse hippocampal DG by ki-67 and DCX immunohistochemistry.This result showed that PPP had anti-aging effects on D-galactoseinduced aging mouse model.Moreover,we observed up-regulated expressions of BDNF and TrkB proteins and down-regulated expressions of Caspase 3,8,and 9 proteins in the PPP-treated mouse hippocampus.Therefore,our results showed that PPP obviously improved neuroblast proliferation and differentiation,and its anti-aging effect might berelated to down-regulation of apoptosis-related proteins,including Caspase 3,8,and 9,via BDNF/TrkB pathway.Our findings provided valuable evidence for its applications in the health and medicine sectors.展开更多
Objective To explore the mechanism of electroacupuncture(EA)at"Fengchi"(GB20)and“Sishencong”(EX-HN 1)on learning and memory impairment in vascular dementia(VD)rats by observing the influences on the N-meth...Objective To explore the mechanism of electroacupuncture(EA)at"Fengchi"(GB20)and“Sishencong”(EX-HN 1)on learning and memory impairment in vascular dementia(VD)rats by observing the influences on the N-methyl-D-aspartate receptor(NMDAR)/cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway and the excitotoxicity induced by hippocampal calcium overload.Methods Thirty-two male SD rats of SPF grade were selected and randomized into a normal group(6 rats),a shamoperation group(6 rats)and an operation group(20 rats).VD model was established with the modified Pulsinelli's four-vessel occlusion(4-VO)method.Twelve rats after successfully modeled were assigned randomly into a model group and an EA group,6 rats in each one.In the EA group,EA was delivered at bilateral"Fengchi"(GB 20)and"Sishencong"(EX-HN 1),with the continuous wave,the frequency of 2 Hz and the electric current of 1 mA.Stimulation intensity was adjusted depending on the slightly trembling of rat head.EA was given once daily,30 min each time;and EA intervention was delivered for 21 days continuously.Using Morris water maze test,the learning and memory functionwas assessed.The neuronal morphology in the hippocampal CAl was observed with HE staining;the level of glutamate(GLU)in serum and hippocampal tissue,as well as the activity of calcium pump(Ca^(2+)-ATP)in the hippocampus were detected using colorimetric method.Theprotein expression ofNMDAR,calmodulindependent protein kinase II(CaMK I),phosphorylated calmodulin-dependent protein kinase I(p-CaMK II),phosphorylated cyclic phosphoradenosine effector element binding proteins(p-CREB),CREB,,and BDNF in the hippocampal CA1 was detected using immunohistochemistry.The protein expression of NMDAR,CREB,p-CREB and BDNF in the hippocampal tissue was detected using Western blot method.Results Compared to the shamoperation group,in the model group,the escape latency was prolonged and the platform crossing times of rats were reduced(P<0.01),the hippocampal neuron structure was damaged to different degrees,the structure in hippocampal CA1 was loosened,the arrangement disorganized,with clear grid-like structure;the neuronal morphology was irregular,pyknosis and even dissolution occurred,glial cells increased,blood capillarywas dilated and the inflammatory cells were infiltrated and scattered.Thelevel of GLUintheserum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated(P<0.01),the activity of Ca^(2+)-ATP and the protein expression of CaMK I,p-CaMK I,CREB,p-CREB and BDNFwere reduced(P<0.01,P<0.05);and the ratio of p-CaMK II/CaMK II and that of p-CREB/CREB were dropped(P<0.05).In comparison with the model group,in the EA group,the escape latency was shortened and the platform crossing times of rats rose(P<0.01),the arrangement was improved in the hippocampal CA1,the neuronal morphology was intact,the nucleoli were relatively clear and the pyknosis or dissolution were attenuated,the numbers of glial cells reduced relatively,the dilation of blood capillary was alleviated.The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue(P<0.01),the activity of Ca^(2+)-ATP and the protein expression of CaMK II,p-CaMK I,CREB,p-CREB and BDNF were elevated(P<0.05,P<0.01);the ratio of p-CaMK II/CaMK II and that of p-CREB/CREB increased(P<0.05).Conclusion EA at"Fengchi"(GB 20)and"Sishencong"(EX-HN 1)can attenuate learning and memory impairment in VD rats,which may be obtained by reducing GLU level in hippocampal tissue,inhibiting hippocampal excitotoxicity,mediating protein expression related to the NMDAR/CREB/BDNFsignalingpathway,and maintaining neuronal survival and growth.展开更多
基金supported by the I+D+i(PID2022-142418OB-C21)grant funded by MICIU/AEI/10.13039/501100011033 and by ERDF/UE.
文摘The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical and non-canonical signaling mechanisms relevant to brain damage.We explore how ErbB signaling is dynamically regulated following injury and how it orchestrates processes such as neuroinflammation,gliosis,and neural repair.Special attention is given to its interplay with other critical pathways,including Notch signaling,and its roles within adult neurogenic niches,where it modulates neural stem cell behavior in response to damage.Based on accumulating preclinical evidence,we propose two therapeutic strategies for targeting ErbB signaling in brain injury:(1)dampening neuroinflammation through ErbB inhibition and(2)promoting neuroprotection and neurogenesis via neuregulin-1-mediated activation.The first strategy is supported by studies,which demonstrate that inhibition of ErbB1 limits neuroinflammation and supports neural repair in preclinical models.The latter strategy is supported by emerging studies demonstrating the significant potential of novel protein kinase C activating diterpenes in modulating ErbB signaling pathways through the regulation of neuregulin-1 release.Diterpenes,by influencing the ErbB pathway,may uniquely bridge the gap between neuroprotection and regeneration.Their potential to modulate inflammation and promote pro-regenerative cellular environments positions them as promising tools in the development of targeted therapies.By dissecting these mechanisms,we aim to shed light on the translational potential of ErbB-targeted therapies and their capacity to enhance endogenous repair processes in the injured brain.
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The University Natural Science Research major Project of Jiangsu Province(Grant No.16KJA310006)
文摘Aging affects the nervous system as well as other organs.In our study,we aimed to study the pharmacological effects and mechanism of porcine placental peptides(PPP)in aging process,and to observe the changes of neuroblast proliferation and differentiation as well as partial gene expression in hippocampus of D-galactose-induced aged mouse.Based on the analysis of experimental results,it was confirmed that PPP significantly improved neurobalst proliferation and differentiation in the mouse hippocampal DG by ki-67 and DCX immunohistochemistry.This result showed that PPP had anti-aging effects on D-galactoseinduced aging mouse model.Moreover,we observed up-regulated expressions of BDNF and TrkB proteins and down-regulated expressions of Caspase 3,8,and 9 proteins in the PPP-treated mouse hippocampus.Therefore,our results showed that PPP obviously improved neuroblast proliferation and differentiation,and its anti-aging effect might berelated to down-regulation of apoptosis-related proteins,including Caspase 3,8,and 9,via BDNF/TrkB pathway.Our findings provided valuable evidence for its applications in the health and medicine sectors.
文摘Objective To explore the mechanism of electroacupuncture(EA)at"Fengchi"(GB20)and“Sishencong”(EX-HN 1)on learning and memory impairment in vascular dementia(VD)rats by observing the influences on the N-methyl-D-aspartate receptor(NMDAR)/cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway and the excitotoxicity induced by hippocampal calcium overload.Methods Thirty-two male SD rats of SPF grade were selected and randomized into a normal group(6 rats),a shamoperation group(6 rats)and an operation group(20 rats).VD model was established with the modified Pulsinelli's four-vessel occlusion(4-VO)method.Twelve rats after successfully modeled were assigned randomly into a model group and an EA group,6 rats in each one.In the EA group,EA was delivered at bilateral"Fengchi"(GB 20)and"Sishencong"(EX-HN 1),with the continuous wave,the frequency of 2 Hz and the electric current of 1 mA.Stimulation intensity was adjusted depending on the slightly trembling of rat head.EA was given once daily,30 min each time;and EA intervention was delivered for 21 days continuously.Using Morris water maze test,the learning and memory functionwas assessed.The neuronal morphology in the hippocampal CAl was observed with HE staining;the level of glutamate(GLU)in serum and hippocampal tissue,as well as the activity of calcium pump(Ca^(2+)-ATP)in the hippocampus were detected using colorimetric method.Theprotein expression ofNMDAR,calmodulindependent protein kinase II(CaMK I),phosphorylated calmodulin-dependent protein kinase I(p-CaMK II),phosphorylated cyclic phosphoradenosine effector element binding proteins(p-CREB),CREB,,and BDNF in the hippocampal CA1 was detected using immunohistochemistry.The protein expression of NMDAR,CREB,p-CREB and BDNF in the hippocampal tissue was detected using Western blot method.Results Compared to the shamoperation group,in the model group,the escape latency was prolonged and the platform crossing times of rats were reduced(P<0.01),the hippocampal neuron structure was damaged to different degrees,the structure in hippocampal CA1 was loosened,the arrangement disorganized,with clear grid-like structure;the neuronal morphology was irregular,pyknosis and even dissolution occurred,glial cells increased,blood capillarywas dilated and the inflammatory cells were infiltrated and scattered.Thelevel of GLUintheserum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated(P<0.01),the activity of Ca^(2+)-ATP and the protein expression of CaMK I,p-CaMK I,CREB,p-CREB and BDNFwere reduced(P<0.01,P<0.05);and the ratio of p-CaMK II/CaMK II and that of p-CREB/CREB were dropped(P<0.05).In comparison with the model group,in the EA group,the escape latency was shortened and the platform crossing times of rats rose(P<0.01),the arrangement was improved in the hippocampal CA1,the neuronal morphology was intact,the nucleoli were relatively clear and the pyknosis or dissolution were attenuated,the numbers of glial cells reduced relatively,the dilation of blood capillary was alleviated.The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue(P<0.01),the activity of Ca^(2+)-ATP and the protein expression of CaMK II,p-CaMK I,CREB,p-CREB and BDNF were elevated(P<0.05,P<0.01);the ratio of p-CaMK II/CaMK II and that of p-CREB/CREB increased(P<0.05).Conclusion EA at"Fengchi"(GB 20)and"Sishencong"(EX-HN 1)can attenuate learning and memory impairment in VD rats,which may be obtained by reducing GLU level in hippocampal tissue,inhibiting hippocampal excitotoxicity,mediating protein expression related to the NMDAR/CREB/BDNFsignalingpathway,and maintaining neuronal survival and growth.
