Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the ant...Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the anterior chamber(AC)structures might play an efferent role in the neural regulation of intraocular pressure(IOP).This study aimed to investigate the anatomic neural connection from the emotional brain to autonomic innervation in the AC.Methods A retrograde trans-multisynaptic pseudorabies virus encoded with an enhanced green fluorescent protein(PRV531)and non-trans-synaptic tracer FAST Dil were injected into the right eye of mice,respectively.Fluorescent localization in the emotional brain and preganglionic nuclei was studied.Five and a half days after PRV531 injection into the right AC,fluorescent signals were observed in several emotional brain regions,including the amygdala,agranular insular cortex,lateral septal nuclei,periaqueductal gray,and hypothalamus.Autonomic preganglionic nuclei,including Edinger-Westphal nucleus,superior salivatory nucleus,and intermediolateral nucleus,were labeled using PRV531.Results The sensory trigeminal nuclei were not labeled using PRV531.The fluorescence signals in the nuclei mentioned above showed bilateral distribution,primarily on the ipsilateral side.Seven days after injecting FAST Dil into the AC,we observed no FAST Dil-labeled neurons in the central nervous system.Conclusion Our results indicate a neural connection from the emotional brain to autonomic innervation in the AC,which provides anatomical support for the emotional influence of IOP via the ANS.展开更多
Helicobacter pylori(H.pylori) infection is a recognized risk factor of dementia, while its role and mechanism in Alzheimer disease(AD) remained unclarified. Our previous study has identified that injection of solu...Helicobacter pylori(H.pylori) infection is a recognized risk factor of dementia, while its role and mechanism in Alzheimer disease(AD) remained unclarified. Our previous study has identified that injection of soluble H.pylori filtrate could induce AD-like pathologic changes and cognitive impairment in SD rats. In the present study, we further explored the effect of long-term stomach colonization of H.pylori bacteria on the brains of SD rats. The results showed that H.pylori bacteria gavage induced an efficient colonization of H.pylori in the stomach after four weeks. However, there was no significant change of tau phosphorylation at Thr205(pT205), Thr231(pT231), Ser396(pS396) and Ser404(pS404) sites in the hippocampus and cerebral cortex. The H.pylori-infected rats also showed no cognitive impairment. These observations may result from inefficient release of bacterial pathogenic factors or the overall lack of host inflammatory responses. We conclude that SD rat with long-term H.pylori colonization in the stomach is not a suitable animal model for exploring the effects of H.pylori infection on brain function in human beings; administration of bacterial filtrates may better reveal the systemic pathologic changes induced by bacterial infection in animals which show a negative host response to bacterial colonization.展开更多
Post-stroke depression(PSD)is a serious and common complication of stroke,which seriously afects the rehabilitation of stroke patients.To date,the pathogenesis of PSD is unclear and efective treatments remain unavaila...Post-stroke depression(PSD)is a serious and common complication of stroke,which seriously afects the rehabilitation of stroke patients.To date,the pathogenesis of PSD is unclear and efective treatments remain unavailable.Here,we established a mouse model of PSD through photothrombosis-induced focal ischemia.By using a combination of brain imaging,transcriptome sequencing,and bioinformatics analysis,we found that the hippocampus of PSD mice had a signifcantly lower metabolic level than other brain regions.RNA sequencing revealed a signifcant reduction of miR34b-3p,which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E(eIF4E).Furthermore,silencing eIF4E inactivated microglia,inhibited neuroinfammation,and abolished the depression-like behaviors in PSD mice.Together,our data demonstrated that insufcient miR34b-3p after stroke cannot inhibit eIF4E translation,which causes PSD by the activation of microglia in the hippocampus.Therefore,miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.展开更多
A transient ischemic attack(TIA)can cause reversible and delayed impairment of cognition,but the specific mechanisms arestill unclear.Annexin al(ANXA1)is a phospholipid-binding protein.Here,we confirmed that cognition...A transient ischemic attack(TIA)can cause reversible and delayed impairment of cognition,but the specific mechanisms arestill unclear.Annexin al(ANXA1)is a phospholipid-binding protein.Here,we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice,and this could be rescued by multiple mild stimulations(MMS).TIA promoted the interaction of ANXAl and CX3CR1,increased the membrane distribution of CX3CR1 in microglila,and thus enhanced the CX3CR1 and CX3CL1 interaction.These phenomena induced by TIA could be reversed by MMS.Meanwhile,the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXAl,and the spine density was significantly reduced in co-cultured microglia overexpressing ANXAl and neurons.Moreover,ANXAl overexpression in microglia abolished the protection of MMS after TIA.Collectively,our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.展开更多
Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy.However,the underlying mechanism remains elusive.We show here that...Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy.However,the underlying mechanism remains elusive.We show here that Pink1 knockout(KO)mice display defective dendritic spine maturation,reduced axonal synaptic vesicles,abnormal synaptic connection,and attenuated long-term synaptic potentiation(LTP).Drp1 activation via ^(S616) phosphorylation rescues deficits of spine maturation in Pink1 KO neurons.展开更多
文摘Objective Previous studies have shown that the autonomic nervous system(ANS),which can be affected by emotions,is important in the occurrence or progression of glaucoma.The autonomic innervation distributed in the anterior chamber(AC)structures might play an efferent role in the neural regulation of intraocular pressure(IOP).This study aimed to investigate the anatomic neural connection from the emotional brain to autonomic innervation in the AC.Methods A retrograde trans-multisynaptic pseudorabies virus encoded with an enhanced green fluorescent protein(PRV531)and non-trans-synaptic tracer FAST Dil were injected into the right eye of mice,respectively.Fluorescent localization in the emotional brain and preganglionic nuclei was studied.Five and a half days after PRV531 injection into the right AC,fluorescent signals were observed in several emotional brain regions,including the amygdala,agranular insular cortex,lateral septal nuclei,periaqueductal gray,and hypothalamus.Autonomic preganglionic nuclei,including Edinger-Westphal nucleus,superior salivatory nucleus,and intermediolateral nucleus,were labeled using PRV531.Results The sensory trigeminal nuclei were not labeled using PRV531.The fluorescence signals in the nuclei mentioned above showed bilateral distribution,primarily on the ipsilateral side.Seven days after injecting FAST Dil into the AC,we observed no FAST Dil-labeled neurons in the central nervous system.Conclusion Our results indicate a neural connection from the emotional brain to autonomic innervation in the AC,which provides anatomical support for the emotional influence of IOP via the ANS.
基金supported by the research foundation from Hubei Health and Family Planning Commission(No.WJ2015MB152)Natural Science Foundation of Hubei Province,China(No.2015CKC897 and No.2017CFA065)+1 种基金National Natural Science Foundation of China(No.81471304 and No.31771189)Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College,HUST
文摘Helicobacter pylori(H.pylori) infection is a recognized risk factor of dementia, while its role and mechanism in Alzheimer disease(AD) remained unclarified. Our previous study has identified that injection of soluble H.pylori filtrate could induce AD-like pathologic changes and cognitive impairment in SD rats. In the present study, we further explored the effect of long-term stomach colonization of H.pylori bacteria on the brains of SD rats. The results showed that H.pylori bacteria gavage induced an efficient colonization of H.pylori in the stomach after four weeks. However, there was no significant change of tau phosphorylation at Thr205(pT205), Thr231(pT231), Ser396(pS396) and Ser404(pS404) sites in the hippocampus and cerebral cortex. The H.pylori-infected rats also showed no cognitive impairment. These observations may result from inefficient release of bacterial pathogenic factors or the overall lack of host inflammatory responses. We conclude that SD rat with long-term H.pylori colonization in the stomach is not a suitable animal model for exploring the effects of H.pylori infection on brain function in human beings; administration of bacterial filtrates may better reveal the systemic pathologic changes induced by bacterial infection in animals which show a negative host response to bacterial colonization.
基金supported by the National Natural Science Foundation of China(81870932,81571078,51627807,31721002,81920208014,31930051)China Postdoctoral Science Foundation Funded Project(2020M672324,2020TQ0113).
文摘Post-stroke depression(PSD)is a serious and common complication of stroke,which seriously afects the rehabilitation of stroke patients.To date,the pathogenesis of PSD is unclear and efective treatments remain unavailable.Here,we established a mouse model of PSD through photothrombosis-induced focal ischemia.By using a combination of brain imaging,transcriptome sequencing,and bioinformatics analysis,we found that the hippocampus of PSD mice had a signifcantly lower metabolic level than other brain regions.RNA sequencing revealed a signifcant reduction of miR34b-3p,which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E(eIF4E).Furthermore,silencing eIF4E inactivated microglia,inhibited neuroinfammation,and abolished the depression-like behaviors in PSD mice.Together,our data demonstrated that insufcient miR34b-3p after stroke cannot inhibit eIF4E translation,which causes PSD by the activation of microglia in the hippocampus.Therefore,miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.
基金This work.was supported bythe National Natural Science Foundation of China(31771126).
文摘A transient ischemic attack(TIA)can cause reversible and delayed impairment of cognition,but the specific mechanisms arestill unclear.Annexin al(ANXA1)is a phospholipid-binding protein.Here,we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice,and this could be rescued by multiple mild stimulations(MMS).TIA promoted the interaction of ANXAl and CX3CR1,increased the membrane distribution of CX3CR1 in microglila,and thus enhanced the CX3CR1 and CX3CL1 interaction.These phenomena induced by TIA could be reversed by MMS.Meanwhile,the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXAl,and the spine density was significantly reduced in co-cultured microglia overexpressing ANXAl and neurons.Moreover,ANXAl overexpression in microglia abolished the protection of MMS after TIA.Collectively,our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.
基金This work was supported by the National Natural Science Foundation of China(31730036,81861138012,81161120498,81429002,31330031,82171506,and 31872778)the Discipline Innovative Engineering Plan(111 Program)of China(B13036)+4 种基金a key laboratory grant from Hunan province(2016TP1006)Science and Technology Major Project of Hunan Provincial Science and Technology Department(2018SK1030)the Department of Science and Technology of Hunan Province(grant 2021DK2001,and innovative team program 2019RS1010)The innovative team program from Department of Science&Technology of Hunan Province(2019RS1010)The innovation-driven team project from Central South University(2020CX016),and Hunan 100 Talents Program.
文摘Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy.However,the underlying mechanism remains elusive.We show here that Pink1 knockout(KO)mice display defective dendritic spine maturation,reduced axonal synaptic vesicles,abnormal synaptic connection,and attenuated long-term synaptic potentiation(LTP).Drp1 activation via ^(S616) phosphorylation rescues deficits of spine maturation in Pink1 KO neurons.