Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking it...Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE pathogenesis.In the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic phases.Dendritic complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early phase.Moreover,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic phase.Furthermore,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic phase.Similarly,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC expression.Primary cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory cytokines.Collectively,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hippocampal dysfunctions in EAE.展开更多
Neurotoxicity induced by stress,radiation,chemicals,or metabolic diseases,is commonly associated with excitotoxicity,oxidative stress,and neuroinflammation.The pathological process of neurotoxicity induces neuronal de...Neurotoxicity induced by stress,radiation,chemicals,or metabolic diseases,is commonly associated with excitotoxicity,oxidative stress,and neuroinflammation.The pathological process of neurotoxicity induces neuronal death,interrupts synaptic plasticity in the brain,and is similar to that of diverse neurodegenerative diseases.Animal models of neurotoxicity have revealed that clinical symptoms and brain lesions can recover over time via neuroregenerative processes.Specifically,brain-derived neurotropic factor（BDNF） and gamma-aminobutyric acid（GABA）-ergic transmission are related to both neurodegeneration and neuroregeneration.This review summarizes the accumulating evidences that suggest a pathogenic role of BDNF and GABAergic transmission,their underlying mechanisms,and the relationship between BDNF and GABA in neurodegeneration and neuroregeneration.This review will provide a comprehensive overview of the underlying mechanisms of neuroregeneration that may help in developing potential strategies for pharmacotherapeutic approaches to treat neurotoxicity and neurodegenerative disease.展开更多
基金supported by the National Research Foundation (NRF)of Korea Grant funded by the Korean Government (NRF-2022R1A2C100402212RS-2023-00219517)。
文摘Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE pathogenesis.In the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic phases.Dendritic complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early phase.Moreover,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic phase.Furthermore,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic phase.Similarly,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC expression.Primary cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory cytokines.Collectively,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hippocampal dysfunctions in EAE.
基金supported by a grant from Wonkwang University in 2017
文摘Neurotoxicity induced by stress,radiation,chemicals,or metabolic diseases,is commonly associated with excitotoxicity,oxidative stress,and neuroinflammation.The pathological process of neurotoxicity induces neuronal death,interrupts synaptic plasticity in the brain,and is similar to that of diverse neurodegenerative diseases.Animal models of neurotoxicity have revealed that clinical symptoms and brain lesions can recover over time via neuroregenerative processes.Specifically,brain-derived neurotropic factor（BDNF） and gamma-aminobutyric acid（GABA）-ergic transmission are related to both neurodegeneration and neuroregeneration.This review summarizes the accumulating evidences that suggest a pathogenic role of BDNF and GABAergic transmission,their underlying mechanisms,and the relationship between BDNF and GABA in neurodegeneration and neuroregeneration.This review will provide a comprehensive overview of the underlying mechanisms of neuroregeneration that may help in developing potential strategies for pharmacotherapeutic approaches to treat neurotoxicity and neurodegenerative disease.
