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Neural Regeneration Research 2024年第11期19卷 2339-2340页

作者： Valerie M.K.Verge Nataliya Tokarska Justin M.Naniong department of anatomy Physiology and PharmacologyUniversity of SaskatchewanSaskatoonSKCanada Cameco MS Neuroscience Research Center University of SaskatchewanSaskatoonSKCanada

Multiple sclerosis(MS)is a debilitating inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration that contribute to *** efficient and effective repair programs following demyelination is a major goal and challenge in *** MS therapies focus largely on modulating the immune aspects of the disease contributing to *** this alleviates some symptoms and mitigates damage,it does not tackle the fundamental challenge of effective remyelination,which few MS patients experience,especially in the progressive phase of the disease.

关键词： sclerosis degeneration damage

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

Filamentation and inhibition of prokaryotic CTP synthase with ligands

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mLife 2024年第2期3卷 240-250页

作者： Chenjun Guo Zixuan Wang Ji‐Long Liu School of Life Science and Technology ShanghaiTech UniversityShanghaiChina department of physiology Anatomy and GeneticsUniversity of OxfordOxfordUK Shanghai Clinical Research and Trial Center ShanghaiChina

Cytidine triphosphate synthase(CTPS)plays a pivotal role in the de novo synthesis of cytidine triphosphate(CTP),a fundamental building block for RNA and DNA that is essential for *** is capable of directly binding to all four nucleotide triphosphates:adenine triphosphate,uridine triphosphate,CTP,and guanidine ***,CTPS can form cytoophidia in vivo and metabolic filaments in vitro,undergoing regulation at multiple *** is considered a potential therapeutic target for combating invasions or infections by viral or prokaryotic *** cryo-electron microscopy,we determined the structure of Escherichia coli CTPS(ecCTPS)filament in complex with CTP,nicotinamide adenine dinucleotide(NADH),and the covalent inhibitor 6-diazo-5-oxo-L-norleucine(DON),achieving a resolution of *** constructed a phylogenetic tree based on differences in filament-forming interfaces and designed a variant to validate our hypothesis,providing an evolutionary perspective on CTPS filament *** computational analysis revealed a solvent-accessible ammonia tunnel upon DON *** comparative structural analysis,we discern a distinct mode of CTP binding of ecCTPS that differs from eukaryotic *** biochemical assays and structural analysis,we determined and validated the synergistic inhibitory effects of CTP with NADH or adenine on *** results expand our comprehension of the diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS.

关键词： CTP synthase Cryo-electron microscopy cytoophidium metabolic filament species specific inhibition

On the functions of astrocyte-mediated neuronal slow inward currents

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Neural Regeneration Research 2024年第12期19卷 2602-2612页

作者： Balázs Pál department of physiology Faculty of MedicineUniversity of DebrecenDebrecenHungary

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of *** events are significantly slower than the excitatory postsynaptic *** of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto *** are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback *** as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological *** is a growing body of evidence on the roles of slow inward currents on a single neuron or local network *** events often occur in synchro ny on neurons located in the same astrocytic *** synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic *** addition,slow inward currents are also subject to non-synaptic plasticity triggered by long-la sting stimulation of the excitatory *** note,there might be important regionspecific differences in the roles and actions triggering slow inward *** greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological *** inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural *** inward currents are significant contributors to paroxysmal depolarizational shifts/interictal *** events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive *** with features overlapping with slow inward currents(excitatory,N-methyl-Dasp

关键词： astrocyte cortical spreading depolarization gliotransmission glutamate neural synchronization NMDA receptor paroxysmal depolarizational shift slow inward current

K^(+) channel-mediated retarded maturation of interneurons and its role in neurodevelopmental disorders

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Neural Regeneration Research 2024年第7期19卷 1403-1404页

作者： Kaizhen Li Daria Savitska Olga Garaschuk Laboratory of Systems Neuroscience Department of PhysiologyUniversity of BernBernSwitzerland Institute of physiology Department of NeurophysiologyEberhard Karls University of TübingenTübingenGermany

De novo mutations in genes encoding K^(+)channels are implicated in many severe neurodevelopmental ***,mutations in KCNA2,encoding the Shaker-type voltage-gated K^(+)channel Kv1.2,and KCNJ2,encoding the inwardly rectifying K^(+)channel Kir2.1,associate with focal and generalized epilepsies,brain atrophy,autism,ataxia and hereditary spastic paraplegia(Syrbe et al.,2015;Masnada et al.,2017;Cheng et al.,2021).

关键词： disorders atrophy

Regenerative medicine strategies for chronic complete spinal cord injury

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Neural Regeneration Research 2024年第4期19卷 818-824页

作者： Shogo Hashimoto Narihito Nagoshi Masaya Nakamura Hideyuki Okano department of Orthopedic Surgery Keio University School of Medicine department of physiology Keio University School of Medicine

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various *** rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete ***,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental *** reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural ***,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe ***,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further ***,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

关键词： cell transplantation chronic phase complete transection regenerative medicine spinal cord injury

Mechanism of Cu entry into the brain:many unanswered questions

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Neural Regeneration Research 2024年第11期19卷 2421-2429页

作者： Shubhrajit Roy Svetlana Lutsenko department of physiology Johns Hopkins University School of MedicineBaltimoreMDUSA

Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical *** requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional *** imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and *** the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well *** review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.

关键词： ATOX1 ATP7A ATP7B blood-brain barrier brain choroid plexus copper SLC31A1

REGENERATION FACTOR 1, a peptide boost for wound healing and plant biotechnology

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Molecular Plant 2024年第9期17卷 1333-1334页

作者： Andreas Schaller University of Hohenheim Department of Plant Physiology and Biochemistry70593 StuttgartGermany

Plants respond to wounding such as caused by insect herbivores by activating their defenses and thus increasing their resistance against attacking pests and opportunistic pathogens(Howe and Schaller,2008).The phenomenon was first described more than 50 years ago by Green and Ryan,who reported that wounding triggers tomato and potato plants to produce proteinase inhibitors that inhibit digestive proteases in the gut of leaf-eating insects to starve them of nutrients(Green and Ryan,1972).They also observed that the accumulation of proteinase inhibitors is not restricted to wounded leaves but occurs throughout the aerial parts of the *** search for a chemical signal that is released locally in response to wounding and that mediates systemic activation of defense gene expression led to the identification of systemin,the first ever peptide with hormonelike activity in plants(Pearce et al.,1991).These seminal findings sparked much research into systemic defense responses and peptide signaling in general,and we know now that systemin is one of many phytocytokines that regulate a multitude of immune responses in plants(Schilmiller and Howe,2005;Gust et al.,2017).

关键词： wound activation defense

Pleiotropic attenuating effect of Ginkgo biloba against isoprenalineinduced myocardial infarction via improving Bcl-2/mTOR/ERK1/2/Na^(+) , K^(+) -ATPase activities

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Chinese Herbal Medicines 2024年第2期16卷 282-292页

作者： Jerome Ndudi Asiwe Abodunrin Adebayo Ojetola Nwoke Enekabokom Ekene Esthinsheen Osirim Anthony Chibuzor Nnamudi Benjamin Oritsemuelebi Jackson Erozueme Onuelu Nicholas Asiwe Harrison Ogheneochuko Eruotor Saviour Inegbenehi department of physiology Delta State UniversityAbraka 1Nigeria department of physiology University of IbadanIbadan 3017Nigeria department of physiology Adeleke UniversityEde 250Nigeria department of Pharmacology Rivers State UniversityNkpolu-Oroworukwo 5080Nigeria department of physiology Redeemer’s UniversityEde 230Nigeria department of Biochemistry PAMO University of Medical SciencesPort Harcourt 500211Nigeria department of Pharmacology Delta State UniversityAbraka 1Nigeria department of anatomy University of Port HarcourtChoba 5323Nigeria department of Medical Laboratory Sciences University of Port HarcourtChoba 5323Nigeria

Objective:Myocardial infarction(MI)is linked to an imbalance in the supply and demand of blood oxygen in the heart ***-blockers and calcium antagonists are just two of the common medications used to treat ***,these have reportedly been shown to be either ineffective or to have undesirable side *** of Ginkgo biloba leaves(GBE),a Chinese herbal product offers special compatibility benefits in therapeutic settings relating to inflammatory diseases and oxidative *** order to better understand how GBE affects MI in rats insulted by isoprenaline(ISO),the current study was ***:The heart weight index,serum lipid profile,cardiac marker enzymes,endogenous antioxidants[catalase(CAT),superoxide dismutase(SOD),glutathione(GSH),nitrites and malondialdehyde(MDA)],inflammatory mediators[tumour necrosis factor alpha(TNF-a)and interleukin-6(IL-6)],immunohistochemical expressions of B-cell lymphoma factor-2(Bcl-2),extracellular signal-regulated kinase(ERK1/2),and mammalian target of rapamycin(mTOR)and histopathological analysis were used to assess the cardioprotective properties of ***:The findings showed that GBE effectively attenuated myocardial infarction by boosting the body’s natural antioxidant defense system and reducing the release of inflammatory cytokines as well as heart injury marker *** expression of Bcl-2,ERK1/2 and mTOR was increased while the histomorphological alterations were ***:The cardioprotective effects of GBE may be due to a mechanism involving increased Bcl-2/mTOR/ERK1/2/Na^(+),K^(+)-ATPase activity.

关键词： antioxidants extracellular signal-regulated kinase Ginkgo biloba extract isoprenaline mammalian target of rapamycin myocardial infarction Na^(+),K^(+)-ATPase

Use of induced pluripotent stem cell-derived brain cells,organoids,assembloids,and blood-brain barrier models in understanding alcohol and anesthetic-induced brain injuries:an emerging perspective

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Neural Regeneration Research 2024年第5期19卷 953-954页

作者： Xiaowen Bai department of Cell Biology Neurobiology&AnatomyMedical College of WisconsinMilwaukeeWIUSA

Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts *** extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain *** perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general *** models could also be used to develop protective and therapeutic approaches.

关键词： injuries protective drugs