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Heterogeneity of mature oligodendrocytes in the central nervous system

Neural Regeneration Research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam M.R.Groh Moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.R.Wayne Moore Jack P.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

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Human umbilical cord Wharton's jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration

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Neural Regeneration Research 2013年第10期8卷 890-899页

作者： Hong Chen Yan Zhang Zhijun Yang Hongtian Zhang Department of Anesthesiology Military General Hospital of Beijing PLA Affiliated Bayi Brain Hospital Military General Hospital of Beijing PLA

Human umbilical mesenchymal stem cells from Wharton＇s jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted into contused rat spinal cords. Immunofluorescence double staining indicated that transplanted cells survived in injured spinal cord, and differentiated into mature and immature oligodendrocyte precursor cells. Biotinylated dextran amine tracing results showed that cell transplantation promoted a higher density of the corticospinal tract in the central and caudal parts of the injured spinal cord. Luxol fast blue and toluidine blue staining showed that the volume of residual myelin was significantly increased at 1 and 2 mm rostral and caudal to the lesion epicenter after cell transplantation. Furthermore, immunofluorescence staining verified that the newly regenerated myelin sheath was derived from the central nervous system. Basso, Beattie and Bresnahan testing showed an evident behavioral recovery. These results suggest that human umbilical mesenchymal stem cell-derived oligodendrocyte precursor cells promote the regeneration of spinal axons and myelin sheaths.

关键词： neural regeneration stem cells spinal cord injury Wharton＇s jelly human umbilical mesenchymalstem cells oligodendrocyte precursor-like cells axon myelin sheath nerve repair grants-supportedpaper neuroregeneration

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Cell vibron polariton resonantly self-confined in the myelin sheath of nerve

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Nano Research 2020年第1期13卷 38-44页

作者： Bo Song Yousheng Shu School of Optical-Electrical Computer Engineering University of Shanghai for Science and TechnologyShanghai200093China State Key Laboratory of Medical Neurobiology Institute for Translational Brain ResearchMOE Frontiers Center for Brain ScienceDepartment of NeurologyHuashan HospitalFudan UniversityShanghai200032China

Polaritons are arousing tremendous interests in physics and material sciences for their unique and amazing properties,especially including the condensation,lasing without inversion and even room-temperature superfluidity.Herein,we propose a cell vibron polariton(cell-VP):a collectively coherent mode of a photon and all phospholipid molecules in a myelin sheath formed by glial cells.Cell-VP can be resonantly self-confined in the myelin sheath under physiological conditions.The observations benefit from the specifically compact,ordered and polar thin-film structure of the sheath,and the relatively strong coupling of the mid-infrared photon with the vibrons of phospholipid tails in the myelin.The underlying physics is revealed to be the collectively coherent superposition of the photon and vibrons,the polariton induced significant enhancement of myelin permittivity,and the resonance of the polariton with the sheath.The captured cell-VPs in myelin sheaths may provide a promising way for super-efficient consumption of extra-weak bioenergy and even directly serve for quantum information.These findings further the understanding of nervous system operations at cellular level from the view of quantum mechanics.

关键词： cell polariton nerves myelin sheath quantum state

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Acetyl-11-keto-beta-boswellic acid promotes sciatic nerve repair after injury: molecular mechanism

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Neural Regeneration Research 2022年第12期17卷 2778-2784页

作者： Yao Wang Zong-Liang Xiong Xiang-Lin Ma Chong Zhou Mo-Han Huo Xiao-Wen Jiang Wen-Hui Yu Department of Veterinary Medicine Northeast Agricultural UniversityHarbinHeilongjiang ProvinceChina College of Life Sciences Northeast Agricultural UniversityHarbinHeilongjiang ProvinceChina Key Laboratory of Heilongjiang Education Department for Common Animal Disease Prevention and Treatment Northeast Agricultural UniversityHarbinHeilongjiang ProvinceChina Institute of Chinese Veterinary Medicine Northeast Agricultural UniversityHarbinHeilongjiang ProvinceChina

Previous studies showed that acetyl-11-keto-beta-boswellic acid(AKBA),the active ingredient in the natural Chinese medicine Boswellia,can stimulate sciatic nerve injury repair via promoting Schwann cell proliferation.However,the underlying molecular mechanism remains poorly understood.In this study,we performed genomic sequencing in a rat model of sciatic nerve crush injury after gastric AKBA administration for 30 days.We found that the phagosome pathway was related to AKBA treatment,and brain-derived neurotrophic factor expression in the neurotrophic factor signaling pathway was also highly up-regulated.We further investigated gene and protein expression changes in the phagosome pathway and neurotrophic factor signaling pathway.Myeloperoxidase expression in the phagosome pathway was markedly decreased,and brain-derived neurotrophic factor,nerve growth factor,and nerve growth factor receptor expression levels in the neurotrophic factor signaling pathway were greatly increased.Additionally,expression levels of the inflammatory factors CD68,interleukin-1β,pro-interleukin-1β,and tumor necrosis factor-αwere also decreased.myelin basic protein-andβ3-tubulin-positive expression as well as the axon diameter-to-total nerve diameter ratio in the injured sciatic nerve were also increased.These findings suggest that,at the molecular level,AKBA can increase neurotrophic factor expression through inhibiting myeloperoxidase expression and reducing inflammatory reactions,which could promote myelin sheath and axon regeneration in the injured sciatic nerve.

关键词： AKBA axon genomics inflammatory injury and repair myelin sheath myeloperoxidase neurotrophic factor peripheral nerve phagosome pathway regeneration Sprague-Dawley rat

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Serum response factor promotes axon regeneration following spinal cord transection injury

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Neural Regeneration Research 2023年第9期18卷 1956-1960页

作者： Guo-Ying Feng Nai-Li Zhang Xiao-Wei Liu Ling-Xi Tong Chun-Lei Zhang Shuai Zhou Lu-Ping Zhang Fei Huang Institute of Neurobiology Binzhou Medical UniversityLaishanShandong ProvinceChina School of Health and Life Sciences University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Studies have snown that serum response factor is beneficaial for axonar regeneration of peripheral herves.However,Its role after central nervous system injury remains unclear. In this study,we established a rat model of T9-T10 spinal cord transection injury.We found that the expression of serum response factor in injured spinal cord gray matter neurons gradually increased with time,reached its peak on the 7^(th) day,and then gradually decreased.To investigate the role of serum response factor,we used lentivirus vecto rs to ove rexpress and silence serum response factor in spinal cord tissue.We found that overexpression of serum response factor promoted motor function recovery in rats with spinal cord injury.Qualitative observation of biotinylated dextran amine anterograde tra cing showed that ove rexpression of serum response factor increased nerve fibers in the injured spinal co rd.Additionally,transmission electron microscopy showed that axon and myelin sheath morphology was restored.Silencing serum response factor had the opposite effects of ove rexpression.These findings suggest that serum response factor plays a role in the recovery of motor function after spinal cord injury.The underlying mechanism may be related to the regulation of axonal regeneration.

关键词： axon growth associated protein 43 motor function myelin sheath neuron regeneration serum response factor spinal cord spinal cord transection

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A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats

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Neural Regeneration Research 2023年第3期18卷 657-663页

作者： Jie Yang Chia-Chen Hsu Ting-Ting Cao Hua Ye Jing Chen Yun-Qing Li Institute of Medical Research Northwestern Polytechnical UniversityXi’anShaanxi ProvinceChina Institute of Biomedical Engineering Department of Engineering ScienceUniversity of OxfordOxfordUK The Oxford Suzhou Centre for Advanced Research(OSCAR) SuzhouJiangsu ProvinceChina Department of Anatomy Histology and Embryology&K.K.Leung Brain Research CentreThe Fourth Military Medical UniversityXi’anShaanxi ProvinceChina Key Laboratory of Brain Science Research and Transformation in Tropical Environment of Hainan Province Hainan Medical UniversityHaikouHainan ProvinceChina Department of Anatomy College of Basic Medical SciencesDali UniversityDaliYunnan ProvinceChina

A hyaluronic acid granular hydrogel can promote neuronal and astrocyte colony formation and axonal extension in vitro,suggesting that the hydrogel can simulate an extracellular matrix structure to promote neural regeneration.However,in vivo experiments have not been conducted.In this study,we transplanted a hyaluronic acid granular hydrogel nerve guidance conduit to repair a 10-mm long sciatic nerve gap.The Basso,Beattie,and Bresnahan locomotor rating scale,sciatic nerve compound muscle action potential recording,Fluoro-Gold retrograde tracing,growth related protein 43/S100 immunofluorescence staining,transmission electron microscopy,gastrocnemius muscle dry/wet weight ratio,and Masson’s trichrome staining results showed that the nerve guidance conduit exhibited similar regeneration of sciatic nerve axons and myelin sheath,and recovery of the electrophysiological function and motor function as autologous nerve transplantation.The conduit results were superior to those of a bulk hydrogel or silicone tube transplant.These findings suggest that tissue-engineered nerve conduits containing hyaluronic acid granular hydrogels effectively promote the morphological and functional recovery of the injured sciatic nerve.The nerve conduits have the potential as a material for repairing peripheral nerve defects.

关键词： functional recovery granular hydrogel hyaluronic acid myelin sheath nerve conduit nerve regeneration peripheral nerve regeneration sciatic nerve injury tissue engineering transection injury

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Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2107-2123页

作者： Huiyang Wang Yueyang Liu Zhenkun Guo Minghui Cui Peng Pang Jingyu Yang Chunfu Wu Department of Pharmacology Shenyang Pharmaceutical UniversityShenyang 110016China

Cognitive impairment caused by chronic cerebral hypoperfusion(CCH)is associated with white matter injury(WMI),possibly through the alteration of autophagy.Here,the autophagy—lysosomal pathway(ALP)dysfunction in white matter(WM)and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion(2VO).The results showed that cognitive impairment occurred by the 28th day after 2VO.Injury and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd day.By the 14th day,abnormal accumulation of autophagy substrate,lysosomal dysfunction,and the activation of mechanistic target of rapamycin(MTOR)pathway were observed in WM,paralleled with mature oligodendrocyte death.This indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal dysfunction.To target the ALP dysfunction,enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1(BECN1)in oligodendrocytes reduced mature oligodendrocyte death,and subsequently alleviated the WMI and cognitive impairment after CCH.These results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO,which was associated with the aggravation of WMI and cognitive impairment.This study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.

关键词： Chronic cerebral hypoperfusion Two vessel occlusion White matter Cognitive impairment Oligodendrocyte myelin sheath Autophagy-lysosomal pathway Mechanistic target of rapamycin

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Biomimetic chitosan scaffolds with long-term controlled release of nerve growth factor repairs 20-mm-long sciatic nerve defects in rats

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Neural Regeneration Research 2022年第5期17卷 1146-1155页

作者： Fa-Dong Liu Hong-Mei Duan Fei Hao Wen Zhao Yu-Dan Gao Peng Hao Zhao-Yang Yang Xiao-Guang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology Capital Medical UniversityBeijingChina Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringBeihang UniversityBeijingChina

Although autogenous nerve transplantation is the gold standard for treating peripheral nerve defects of considerable length,it still has some shortcomings,such as insufficient donors and secondary injury.Composite chitosan scaffolds loaded with controlled release of nerve growth factor can promote neuronal survival and axonal regeneration after short-segment sciatic nerve defects.However,the effects on extended nerve defects remain poorly understood.In this study,we used chitosan scaffolds loaded with nerve growth factor for 8 weeks to repair long-segment(20 mm)sciatic nerve defects in adult rats.The results showed that treatment markedly promoted the recovery of motor and sensory functions.The regenerated sciatic nerve not only reconnected with neurons but neural circuits with the central nervous system were also reconstructed.In addition,the regenerated sciatic nerve reconnected the motor endplate with the target muscle.Therefore,this novel biomimetic scaffold can promote the regeneration of extended sciatic nerve defects and reconstruct functional circuits.This provides a promising method for the clinical treatment of extended peripheral nerve injury.This study was approved by the Animal Ethics Committee of Capital Medical University,China(approval No.AEEI-2017-033)on March 21,2017.

关键词： axon chitosan functional recovery myelin sheath nerve growth factor peripheral nerve injury pseudorabies virus regeneration scaffold sciatic nerve

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Reduced graphene oxide-embedded nerve conduits loaded with bone marrow mesenchymal stem cell-derived extracellular vesicles promote peripheral nerve regeneration

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Neural Regeneration Research 2023年第1期18卷 200-206页

作者： Wei Zhang Xing-Xing Fang Qi-Cheng Li Wei Pi Na Han Department of Orthopedics and Trauma Peking University People’s HospitalBeijingChina National Center for Trauma Medicine BeijingChina Central Laboratory Peking University People’s HospitalBeijingChina

We previously combined reduced graphene oxide(rGO)with gelatin-methacryloyl(GelMA)and polycaprolactone(PCL)to create an rGO-GelMA-PCL nerve conduit and found that the conductivity and biocompatibility were improved.However,the rGO-GelMA-PCL nerve conduits differed greatly from autologous nerve transplants in their ability to promote the regeneration of injured peripheral nerves and axonal sprouting.Extracellular vesicles derived from bone marrow mesenchymal stem cells(BMSCs)can be loaded into rGO-GelMA-PCL nerve conduits for repair of rat sciatic nerve injury because they can promote angiogenesis at the injured site.In this study,12 weeks after surgery,sciatic nerve function was measured by electrophysiology and sciatic nerve function index,and myelin sheath and axon regeneration were observed by electron microscopy,immunohistochemistry,and immunofluorescence.The regeneration of microvessel was observed by immunofluorescence.Our results showed that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles were superior to rGO-GelMA-PCL conduits alone in their ability to increase the number of newly formed vessels and axonal sprouts at the injury site as well as the recovery of neurological function.These findings indicate that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles can promote peripheral nerve regeneration and neurological function recovery,and provide a new direction for the curation of peripheral nerve defect in the clinic.

关键词： angiogenesis axon bone mesenchymal stem cell extracellular vesicles hybrid nanofibers myelin sheath nerve conduit neurological function peripheral nerve injury reduced graphene oxide

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Insights into myelin dysfunction in schizophrenia and bipolar disorder

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World Journal of Psychiatry 2022年第2期12卷 264-285页

作者： Marcela Valdés-Tovar Alejandra Monserrat Rodríguez-Ramírez Leslye Rodríguez-Cárdenas Carlo E Sotelo-Ramírez Beatriz Camarena Marco Antonio Sanabrais-Jiménez Héctor Solís-Chagoyán Jesús Argueta Germán Octavio López-Riquelme Departamento de Farmacogenética Subdirección de Investigaciones ClínicasInstituto Nacional de Psiquiatría Ramón de la Fuente MuñizMexico City 14370Mexico Departamento de Farmacogenética Instituto Nacional de Psiquiatría Ramón de la Fuente MuñizMexico City 14370Mexico Doctorado en Biología Experimental Universidad Autónoma Metropolitana-IztapalapaMexico City 09340Mexico Laboratorio de Neurofarmacología Instituto Nacional de Psiquiatría Ramón de la Fuente MuñizMexico City 14370Mexico Laboratorio de Socioneurobiología Centro de Investigación en Ciencias CognitivasUniversidad del Estado de MorelosCuernavaca 62209MorelosMexico

Schizophrenia and bipolar disorder are disabling psychiatric disorders with a worldwide prevalence of approximately 1%.Both disorders present chronic and deteriorating prognoses that impose a large burden,not only on patients but also on society and health systems.These mental illnesses share several clinical and neurobiological traits;of these traits,oligodendroglial dysfunction and alterations to white matter(WM)tracts could underlie the disconnection between brain regions related to their symptomatic domains.WM is mainly composed of heavily myelinated axons and glial cells.myelin internodes are discrete axon-wrapping membrane sheaths formed by oligodendrocyte processes.myelin ensheathment allows fast and efficient conduction of nerve impulses through the nodes of Ranvier,improving the overall function of neuronal circuits.Rapid and precisely synchronized nerve impulse conduction through fibers that connect distant brain structures is crucial for higher-level functions,such as cognition,memory,mood,and language.Several cellular and subcellular anomalies related to myelin and oligodendrocytes have been found in postmortem samples from patients with schizophrenia or bipolar disorder,and neuroimaging techniques have revealed consistent alterations at the macroscale connectomic level in both disorders.In this work,evidence regarding these multilevel alterations in oligodendrocytes and myelinated tracts is discussed,and the involvement of proteins in key functions of the oligodendroglial lineage,such as oligodendrogenesis and myelination,is highlighted.The molecular components of the axo-myelin unit could be important targets for novel therapeutic approaches to schizophrenia and bipolar disorder.

关键词： myelin sheath Oligodendroglia Schizophrenia Bipolar disorder White matter

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