Changes in structural plasticity of hippocampal neurons in an animal model of multiple sclerosis  

作　　者：Poornima D.E.Weerasinghe-Mudiyanselage Sohi Kang Joong-Sun Kim Sung-Ho Kim Hongbing Wang Taekyun Shin Changjong Moon 

机构地区：[1]Department of Veterinary Anatomy and Animal Behavior,College of Veterinary Medicine and BK21 FOUR Program,Chonnam National University,Gwangju 61186,Republic of Korea [2]Department of Anatomy and Convergence Medical Science,Institute of Health Sciences,College of Medicine,Gyeongsang National University,Jinju 52727,Republic of Korea [3]Department of Physiology and Neuroscience Program,Michigan State University,East Lansing,MI 48824,USA [4]Department of Veterinary Anatomy,College of Veterinary Medicine and Veterinary Medical Research Institute,Jeju National University,Jeju 63243,Republic of Korea

出　　处：《Zoological Research》2024年第2期398-414,共17页动物学研究（英文）

基　　金：supported by the National Research Foundation (NRF)of Korea Grant funded by the Korean Government (NRF-2022R1A2C100402212;RS-2023-00219517)。

摘　　要：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.

关 键 词：Activity-regulated cytoskeleton-associated protein Anxiety-like behavior Experimental autoimmune encephalomyelitis Hippocampal dysfunction NEUROINFLAMMATION 

分 类 号：R744.51[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]