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

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Zoological Research 2024年第2期45卷 398-414页

作者： Poornima D.E.Weerasinghe-Mudiyanselage Sohi Kang Joong-Sun Kim Sung-Ho Kim Hongbing Wang Taekyun Shin changjong moon Department of Veterinary Anatomy and Animal Behavior College of Veterinary Medicine and BK21 FOUR ProgramChonnam National UniversityGwangju 61186Republic of Korea Department of Anatomy and Convergence Medical Science Institute of Health SciencesCollege of MedicineGyeongsang National UniversityJinju 52727Republic of Korea Department of Physiology and Neuroscience Program Michigan State UniversityEast LansingMI 48824USA Department of Veterinary Anatomy College of Veterinary Medicine and Veterinary Medical Research InstituteJeju National UniversityJeju 63243Republic of Korea

Structural plasticity is critical for the functional diversity of neurons in the *** 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 *** 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 *** 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 ***,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 ***,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 ***,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC *** cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory ***,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 hi

关键词： Activity-regulated cytoskeleton-associated protein Anxiety-like behavior Experimental autoimmune encephalomyelitis Hippocampal dysfunction Neuroinflammation

Neurotoxicity of cancer chemotherapy

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Neural Regeneration Research 2013年第17期8卷 1606-1614页

作者： Miyoung Yang changjong moon Department of Veterinary Anatomy College of Veterinary Medicine and Animal Medical Institute Chonnam National University Department of Physiology and Neuroscience Program Michigan State University

There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causa mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.

关键词： neural regeneration reviews neurogenesis behavioral dysfunction chemotherapy hippocampaldysfunction memory deficit mood disorder neurodegeneration neuron neuroplasticity neurotoxicity grants-supported paper neuroregeneration

Intravenous morphine self-administration alters accumbal microRNA profiles in the mouse brain

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Neural Regeneration Research 2018年第1期13卷 77-85页

作者： Juhwan Kim Heh-In Im changjong moon Department of Veterinary Anatomy and Animal Behavior College of Veterinary Medicine and BK21 Plus Project Team Chonnam National University Gwangju South Korea Center for Neuroscience Korea Institute of Science and Technology (KIST) Seoul South Korea Convergence Research Center for Diagnosis Treatment and Care System of Dementia Korea Institute of Science and Technology (KIST) Seoul South Korea Division of Biomedical Science & Technology KIST School Korea University of Science and Technology Seoul South Korea

A significant amount of evidence indicates that microRNAs （miRNAs） play an important role in drug addiction. The nucleus accumbens （NAc） is a critical part of the brain’s reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of miRNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine （0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion） and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered miRNAs and their putative target mRNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway mapping and CyTargetLinker. We found that 62 miRNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine （receptor internalization/endocytosis）. The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction.

关键词： nerve regeneration nucleus accumbens microRNA morphine self-administration bioinformatics neural regeneration

Effects of cancer therapy on hippocampus-related function

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Neural Regeneration Research 2015年第10期10卷 1572-1573页

作者： Miyoung Yang changjong moon Department of Anatomy School of Medicine Wonkwang University Department of Veterinary Anatomy and Animal Behavior College of Veterinary Medicine Chonnam National University

Cancer treatments such as chemotherapy and radiotherapy are widely used to treat primary and metastatic *** studies have demonstrated that these types of treatment can effectively and successfully extend the lifespan of cancer patients,but they are also associated with various neurological complications such as cognitive deficits, seizures, and emotional problems （Taphoorn and Klein, 2004; Yang and moon, 2013; Son et al., 2015b）.

关键词： Effects of cancer therapy on hippocampus-related function MTX BDNF

Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment

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Neural Regeneration Research 2012年第21期7卷 1651-1658页

作者： Miyoung Yang Juhwan Kim Sung-Ho Kim Joong-Sun Kim Taekyun Shin changjong moon Department of Veterinary Anatomy College of Veterinary Medicine and Animal Medical Institute Chonnam National University Department of Experimental Radiation Research Center Dongnam Institute of Radiological & Medical Sciences (DIRAMS) Department of Veterinary Anatomy College of Veterinary Medicine Jeju National University

Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate （40 mg/kg） intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyI-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase （1 day post-injection）, while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the eady （1 day post-injection） and late phases （7-14 days post-injection）. Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase （7-14 days post-injection）. Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.

关键词： hippocampus methotrexate neurotrophic factor synaptic plasticity-related signal neuralregeneration

Brain-derived neurotropic factor and GABAergic transmission in neurodegeneration and neuroregeneration

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Neural Regeneration Research 2017年第10期12卷 1733-1741页

作者： Jinwook Kim Sueun Lee Sohi Kang Sung-Ho Kim Jong-Choon Kim Miyoung Yang changjong moon Departments of Veterinary Anatomy and Veterinary Toxicology College of Veterinary Medicine and BK21 PLUS Project TeamChonnam National University Department of Anatomy School of Medicine and Institute for Environmental ScienceWonkwang University

Neurotoxicity induced by stress,radiation,chemicals,or metabolic diseases,is commonly associated with excitotoxicity,oxidative stress,and *** pathological process of neurotoxicity induces neuronal death,interrupts synaptic plasticity in the brain,and is similar to that of diverse neurodegenerative *** models of neurotoxicity have revealed that clinical symptoms and brain lesions can recover over time via neuroregenerative ***,brain-derived neurotropic factor（BDNF） and gamma-aminobutyric acid（GABA）-ergic transmission are related to both neurodegeneration and *** 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 *** 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.

关键词： brain-derived neurotropic factor neurotoxicity gamma-aminobutyric acid-ergic transmission neurodegenerative diseases neural regeneration

Ninjurin-1: a biomarker for reflecting the process of neuroinflammation after spinal cord injury

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Neural Regeneration Research 2021年第7期16卷 1331-1335页

作者： Poornima D.E.Weerasinghe-Mudiyanselage Jeongtae Kim Yuna Choi changjong moon Taekyun Shin Meejung Ahn Department of Veterinary Anatomy College of Veterinary Medicine and Veterinary Medical Research InstituteJeju National UniversityJejuRepublic of Korea Department of Veterinary Anatomy College of Veterinary Medicine and BK21 Plus Project TeamChonnam National UniversityGwangjuRepublic of Korea Department of Anatomy Kosin University College of MedicineBusanRepublic of Korea Department of Animal Science College of Life ScienceSangji UniversityWonjuRepublic of Korea

Previous studies have shown that Ninjurin-1 participates in cell trafficking and axonal growth following central and peripheral nervous system *** its precise roles in these processes and involvement in spinal cord injury pathophysiology remain *** blot assay revealed that Ninjurin-1 levels in rats with spinal cord injury exhibited an upregulation until day 4 post-injury and slightly decreased thereafter compared with sham *** analysis revealed that Ninjurin-1 immunoreactivity in rats with spinal cord injury sharply increased on days 1 and 4 post-injury and slightly decreased on days 7 and 21 post-injury compared with sham ***-1 immunostaining was weak in vascular endothelial cells, ependymal cells, and some glial cells in sham controls while it was relatively strong in macrophages, microglia, and reactive *** findings suggest that a variety of cells, including vascular endothelial cells, macrophages, and microglia, secrete Ninjurin-1 and they participate in the pathophysiology of compression-induced spinal cord *** experimental procedures were approved by the Care and Use of Laboratory Animals of Jeju National University(approval No.2018-0029) on July 6, 2018.

关键词： astrocytes clip compression injury macrophage microglia neuroinflammation Ninjurin-1 rat spinal cord

Epigenetic mechanisms involved in the neuroprotective effect of scorpion extract in a Parkinson's disease murine model based on multi-omics approach

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Journal of Traditional Chinese Medicine 2021年第3期41卷 390-396页

作者： Joong Sun Kim Hye-Sun Lim Byeong Cheol moon Mary Jasmin Ang Sung-Ho Kim changjong moon Boseok Seong Yunji Jang Hyung-Yong Kim Chul Kim Herbal Medicine Resources Research Center Korea Institute of Oriental MedicineJeollanamdo 58245Republic of Korea College of Veterinary Medicine and BK21 Plus Project Team Chonnam National UniversityGwangju 61186Republic of Korea Future Medicine Division Korea Institute of Oriental MedicineDaejeon 34054Republic of Korea Research and Development Center Insilicogen Inc.Yonginsi 16954Republic of Korea

OBJECTIVE: To investigate whether scorpion extract elicits a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated mice models, and the genes associated with the therapeutic effects using RNA sequencing(seq)***: This study investigated the changes in interaction between messenger ribonucleic acid(m RNA) expression and deoxyribonucleic acid(DNA) methylation related to the protective effects of scorpion extracts, in the substantia nigra(SN)region of a MPTP-induced Parkinson's disease(PD)***: In this model, scorpion extracts attenuated the motor impairment as demonstrated by the rotarod and open field tests. Scorpion extracts consistently attenuated the decrease of tyrosine hydroxylase(TH) positive neural cells in the SN and striatum of mice. We profiled genomewide DNA methylation using Methyl-Seq and measured the transcriptome using RNA-Seq in murine SN in the following groups: vehicle-treated MPTP-induced PD mice and scorpion extracttreated MPTP-induced PD mice. In total, 13 479 differentially expressed genes were identified in association with the anti-PD effect of the scorpion extract, mainly in the promoter and coding *** them, 47 were negatively correlated downregulated genes. Nineteen genes out of 47 downregulated genes were negatively correlated with the expression of the other 28 genes. Among these genes, SGSM1 was related to dopaminergic neurons including dopamine transporters, TH, dihydroxyphenylalanine decarboxylase, and dopamine D2 ***: This study provides insights into the anti-parkinsonian effects of scorpion extract and reveals the epigenetic targets in its therapeutic mechanism.

关键词： scorpions 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine Parkinson disease DNA methylation

Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression

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Neural Regeneration Research 2019年第9期14卷 1530-1535页

作者： Hae June Lee Yeonghoon Son Minyoung Lee changjong moon Sung Ho Kim In Sik Shin Miyoung Yang Sangwoo Bae Joong Sun Kim Division of Basic Radiation Bioscience Korea Institute of Radiological&Medical Sciences(KIRMAS)SeoulRepublic of Korea National Primate Research Center Korea Research Institute of Bioscience and Biotechnology(KRIBB)CheongjuRepublic of Korea College of Pharmacy Kyungpook National UniversityDaeguRepublic of Korea College of Veterinary Medicine Veterinary Medical Research InstituteChonnam National UniversityGwangjuRepublic of Korea School of Medicine Wonkwang UniversityJeonbukRepublic of Korea Research Center Dongnam Institute of Radiological&Medical Sciences(DIRAMS)BusanRepublic of Korea

Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain *** investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial *** impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after *** also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic ***-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor *** butyrate pretreatment reversed these *** findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor *** study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval ***16-0002)on December 30,2016.

关键词： sodium butyrate radioprotector ionizing radiation hippocampal damage cAMP response element binding brain-derived neurotrophic factor histone deacetylase inhibitor neurogenesis