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 in...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.展开更多
Salvianolic acid B,an active pharmaceutical compound present in Salvia miltiorrhiza,exerts a neuroprotective effect in animal models of brain and spinal cord injury.Salvianolic acid B can promote recovery of neurologi...Salvianolic acid B,an active pharmaceutical compound present in Salvia miltiorrhiza,exerts a neuroprotective effect in animal models of brain and spinal cord injury.Salvianolic acid B can promote recovery of neurological function;however,its protective effect on the myelin sheath after spinal cord injury remains poorly understood.Thus,in this study,in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation,and the most effective dose was 20 μg/m L.For in vivo investigation,rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks.The amount of myelin sheath and the number of regenerating axons increased,neurological function recovered,and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats.These results indicate that salvianolic acid B can protect axons and the myelin sheath,and can promote the recovery of neurological function.Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.展开更多
In the present study,tissue blocks were randomly sampled from the entire hippocampus of 6-week-old Long-Evans rats.Isotropic,uniform and random sections,60 nm thick,were prepared by isector.Fifteen fields of view were...In the present study,tissue blocks were randomly sampled from the entire hippocampus of 6-week-old Long-Evans rats.Isotropic,uniform and random sections,60 nm thick,were prepared by isector.Fifteen fields of view were randomly selected for each section and photographed using a transmission electron microscope.The mean internal and external diameters of the myelin sheaths were obtained by measuring the longest profile diameter perpendicular to its longest axis.The inner and outer perimeters of the myelin sheaths were estimated using the equidistant parallel test lines.The thickness of the myelin sheaths was estimated by direct orthogonal measurements in uniform,random locations.These stereological methods should permit an unbiased quantitative assessment of changes in the myelin sheaths of myelinated fibers in the hippocam-pus.展开更多
Schizophrenia,as a common mental disease,seriously threatens the physical and mental health of human beings.It is characterized by many mental and behavioral disorders,such as uncoordinated thinking and emotional mode...Schizophrenia,as a common mental disease,seriously threatens the physical and mental health of human beings.It is characterized by many mental and behavioral disorders,such as uncoordinated thinking and emotional mode which separated from the actual living environment.Patients with schizophrenia are prone to relapse and deterioration due to their long course of disease,resulting in the loss of labor force.It has been proved that the occurrence and development of schizophrenia is closely related to the abnormal development of oligodendrocytes,which have the function of myelin formation and the dysfunction of myelin sheath itself.For a comprehensive understanding of myelin abnormal effects on the pathogenesis of schizophrenia,this paper is to review the literature,then summarize and discuss the animal experimental literature related to the abnormal myelin sheath in schizophrenia from the perspectives of behavioristics,neuroimaging,protein expression and stereology,in order to further clarify the influence of the abnormal myelin sheath on the pathogenesis of schizophrenia and provide ideas for the diagnosis of schizophrenia and the research and development of new drugs.展开更多
More than any other organs,brain energy demand is entirely dependent on glucose catabolism through the oxidative phosphorylation（OXPHOS）.Glucose is the major cerebral energy substrate in the nervous system（NS）.Ket...More than any other organs,brain energy demand is entirely dependent on glucose catabolism through the oxidative phosphorylation（OXPHOS）.Glucose is the major cerebral energy substrate in the nervous system（NS）.Ketone bodies can be utilized as an additional substrate,but in any case,neurons critically depend on oxygen supply.展开更多
Over the recent years, it has been found that microglia pseudopodia contact synapses, detect sick ones and prune them, even in adult animals. Myelinated nerves also carry out plasticity in which microglia remove myeli...Over the recent years, it has been found that microglia pseudopodia contact synapses, detect sick ones and prune them, even in adult animals. Myelinated nerves also carry out plasticity in which microglia remove myelin debris by phagocytosis. However, it remains unknown whether microglia explore structures on nerve fibers, such as Ranvier’s node(RN) or myelin sheath, before they become debris. By double or triple staining RNs or myelin sheathes and microglia in healthy rat corpus callosum, this study unveiled direct contacts of microglia pseudopodia with RNs and with para-and inter-nodal myelin sheathes, which was then verified by electron microscopic observations. Our data indicated that microglia also explore unmyelinated nerve fibers. Furthermore, we used the animals with matured white matter;therefore, microglia may be actively involved in plasticity of matured white matter tracts as it does for synapse pruning, instead of only passively phagocytize myelin debris.展开更多
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 superfluid...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.展开更多
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 functio...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 interventions targeting varied central nervous system pathology.展开更多
Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI ...Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous trans-plantation ability.This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI.The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury.BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors,extracellular matrix molecules,and adhesion molecules.Additionally,BMSCs release pro-angiogenic factors to promote the formation of new blood vessels.They modulate cytokine expression and regulate macrophage polarization,leading to immunomodulation.Furthermore,BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration,thereby promoting neuronal repair and regeneration.Moreover,this review explores methods of applying BMSCs in PNI treatment,including direct cell trans-plantation into the injured neural tissue,implantation of BMSCs into nerve conduits providing support,and the application of genetically modified BMSCs,among others.These findings confirm the potential of BMSCs in treating PNI.However,with the development of this field,it is crucial to address issues related to BMSC therapy,including establishing standards for extracting,identifying,and cultivating BMSCs,as well as selecting application methods for BMSCs in PNI such as direct transplantation,tissue engineering,and genetic engineering.Addressing these issues will help translate current preclinical research results into clinical practice,providing new and effective treatment strategies for patients with PNI.展开更多
The present study established a chronic experimental autoimmune encephalomyelitis model in C57BL/6 mice induced by myelin oligodendrocyte glycoprotein peptides and complete Freund＇s adjuvant. Onset latency was 12 day...The present study established a chronic experimental autoimmune encephalomyelitis model in C57BL/6 mice induced by myelin oligodendrocyte glycoprotein peptides and complete Freund＇s adjuvant. Onset latency was 12 days, with an incidence rate of 100%. Neuropathological characteristics included perivascular inflammatory cell infiltration, demyelination, neuronal degeneration, and axonal damage within cerebral and myelic white matter. Electron microscopy revealed swollen mitochondria, complete organ disappearance, and fused or broken myelin sheath structure, which were accompanied by myelin sheath reconstruction. Moreover, axonal damage was not consistent with demyelination distribution, and severity of axonal damage did not correlate with demyelination. Results suggested that axonal damage in an experimental autoimmune encephalomyelitis model is not secondary to inflammatory demyelination.展开更多
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 ...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.展开更多
BACKGROUND： Myelination is a process whereby glial cells identify, adhere, wrap and enclose axons to form a spiral myelin sheath. OBJECTIVE： To investigate the effects of action potential-simulated weak electric fie...BACKGROUND： Myelination is a process whereby glial cells identify, adhere, wrap and enclose axons to form a spiral myelin sheath. OBJECTIVE： To investigate the effects of action potential-simulated weak electric fields on myelination in the central nervous system. DESIGN AND SETTING： This single-sample observation study was performed at the 324 Hospital of Chinese PLA. MATERIALS： Two 5 μm carbon fibers were provided by the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. One Sprague Dawley rat, aged 1 day, was used. METHODS： Cerebral cortex was harvested from the rat to prepare a suspension [（1 2）× 10^5/mL] containing neurons and glial cells. To simulate the axon, carbon fibers were placed at the bottom of the neuron-glial cell coculture dish, and were electrified with a single phase square wave current, 1×10^-2, 1×10^-3, 1×10^-4, and 1×10^-5 seconds, 1 Hz, 40 mV, and 10 μA, 30 minutes each, once a day for 10 consecutive days to simulate weak negative electric fields during action potential conduction. MAIN OUTCOME MEASURES： Glial cell growth and wrapping of carbon fibers were observed by phase contrast microscopy and immunohistochemistry. RESULTS： On culture day 7, cell groups were found to adhere to negative carbon fibers in the 1 × 10^-3 seconds square wave group. Cell membrane-like substances grew out of cell groups, wrapped the carbon fibers, and stretched to the ends of carbon fibers. Only some small and round cells close to negative carbon fibers were found on culture day 12. In the 1 × 10^-4 and 1 × 10^-3 seconds square wave groups, the negative carbon fibers were wrapped by oligodendrocytes or their progenitor cells. CONCLUSION： The local negative electric field which is generated by action potentials at 1×（10^-4-10^-3） seconds, 40 mV can directly initiate and participate in myelination in the central nervous system.展开更多
Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarin...Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury.The right common carotid artery of 3-day-old rats was ligated for 2 hours.The rats were then prewarmed in a plastic container with holes in the lid,which was placed in 37°C water bath for 30 minutes.Afterwards,the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models.The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days.At 22 days after birth,rosmarinic acid was found to improve motor,anxiety,learning and spatial memory impairments induced by hypoxia/ischemia injury.Furthermore,rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone.After hypoxia/ischemia injury,rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure.Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2.These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum.This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University,China (approval No.20161636721) on September 16,2017.展开更多
An animal model of cortical dysplasia was established through X-ray irradiation induced subcortical heterotopic nodules in rats. Transmission electron microscopy detection of the ultrastructure and the stereology exam...An animal model of cortical dysplasia was established through X-ray irradiation induced subcortical heterotopic nodules in rats. Transmission electron microscopy detection of the ultrastructure and the stereology examination showed that there was a significant decrease in cerebral white matter and hippocampal volume, the total volume, volume density, length density and total length of the myelinated fibers in the white matter of cortical dysplasia rats. Subcortical heterotopic nodules of the hippocampal CA1 region and synaptic number density in the CA3 region were reduced compared with normal rats. Our experimental findings indicate that erosed subcortical heterotopic nodules, decreased total length of myelinated nerve fibers and demyelination directly lead to a reduction of white matter volume.展开更多
基金supported by the National Natural Science Foundation of China, No. 81100916, 30400464,81271316the Postdoctoral Science Foundation of China,No. 201104901907
文摘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.
基金supported by a grant of Guangdong Medical University of China,No.XB1380
文摘Salvianolic acid B,an active pharmaceutical compound present in Salvia miltiorrhiza,exerts a neuroprotective effect in animal models of brain and spinal cord injury.Salvianolic acid B can promote recovery of neurological function;however,its protective effect on the myelin sheath after spinal cord injury remains poorly understood.Thus,in this study,in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation,and the most effective dose was 20 μg/m L.For in vivo investigation,rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks.The amount of myelin sheath and the number of regenerating axons increased,neurological function recovered,and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats.These results indicate that salvianolic acid B can protect axons and the myelin sheath,and can promote the recovery of neurological function.Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.
基金the National Natural Science Foundation of China,No.30973155
文摘In the present study,tissue blocks were randomly sampled from the entire hippocampus of 6-week-old Long-Evans rats.Isotropic,uniform and random sections,60 nm thick,were prepared by isector.Fifteen fields of view were randomly selected for each section and photographed using a transmission electron microscope.The mean internal and external diameters of the myelin sheaths were obtained by measuring the longest profile diameter perpendicular to its longest axis.The inner and outer perimeters of the myelin sheaths were estimated using the equidistant parallel test lines.The thickness of the myelin sheaths was estimated by direct orthogonal measurements in uniform,random locations.These stereological methods should permit an unbiased quantitative assessment of changes in the myelin sheaths of myelinated fibers in the hippocam-pus.
基金National Natural Science Foundation of China(No.81973747,81873299)Applied Technology Research and Development Program of Heilongjiang Province(No.GZ16C001)Traditional Chinese Medicine Science and Technology Project of Heilongjiang Province(No.ZHY2020-183).
文摘Schizophrenia,as a common mental disease,seriously threatens the physical and mental health of human beings.It is characterized by many mental and behavioral disorders,such as uncoordinated thinking and emotional mode which separated from the actual living environment.Patients with schizophrenia are prone to relapse and deterioration due to their long course of disease,resulting in the loss of labor force.It has been proved that the occurrence and development of schizophrenia is closely related to the abnormal development of oligodendrocytes,which have the function of myelin formation and the dysfunction of myelin sheath itself.For a comprehensive understanding of myelin abnormal effects on the pathogenesis of schizophrenia,this paper is to review the literature,then summarize and discuss the animal experimental literature related to the abnormal myelin sheath in schizophrenia from the perspectives of behavioristics,neuroimaging,protein expression and stereology,in order to further clarify the influence of the abnormal myelin sheath on the pathogenesis of schizophrenia and provide ideas for the diagnosis of schizophrenia and the research and development of new drugs.
基金Grant from the"Fondazione Giuseppe Levi–Accademia Nazionale dei Lincei"for the research project entitled:"Produzione extramitocondriale di ATP in mielina:localizzazione dei complessi della catena respiratoria e possible ruolo nella degenerazione assonale in Sclerosi Multipla",No.Borsa"Giuseppe Levi"_2013the‘‘Compagnia di San Paolo’’-Neuroscience Program,for the research project entitled:‘‘Energetic metabolism in myelinated axon:a new trophic role of myelin sheath’’,No.2008.1142
文摘More than any other organs,brain energy demand is entirely dependent on glucose catabolism through the oxidative phosphorylation（OXPHOS）.Glucose is the major cerebral energy substrate in the nervous system（NS）.Ketone bodies can be utilized as an additional substrate,but in any case,neurons critically depend on oxygen supply.
基金supported by R01 NS063878 and P30 MH062261 (to H.X., H.S.F.)
文摘Over the recent years, it has been found that microglia pseudopodia contact synapses, detect sick ones and prune them, even in adult animals. Myelinated nerves also carry out plasticity in which microglia remove myelin debris by phagocytosis. However, it remains unknown whether microglia explore structures on nerve fibers, such as Ranvier’s node(RN) or myelin sheath, before they become debris. By double or triple staining RNs or myelin sheathes and microglia in healthy rat corpus callosum, this study unveiled direct contacts of microglia pseudopodia with RNs and with para-and inter-nodal myelin sheathes, which was then verified by electron microscopic observations. Our data indicated that microglia also explore unmyelinated nerve fibers. Furthermore, we used the animals with matured white matter;therefore, microglia may be actively involved in plasticity of matured white matter tracts as it does for synapse pruning, instead of only passively phagocytize myelin debris.
基金supported by the National Natural Science Foundation of China(Nos.31630029 and 31661143037)the National Key Research and Development Program of China(No.2018YFE0205501)the National Supercomputer Center in Tianjin,and dedicated to the memory of B.S.’s mother.
文摘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.
基金supported by a grant from the Progressive MS Alliance(BRAVE in MS)Le Grand Portage Fund。
文摘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 interventions targeting varied central nervous system pathology.
基金CAMS Innovation Fund for Medical Sciences,No.2022-I2M-C&T-B-034.
文摘Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous trans-plantation ability.This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI.The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury.BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors,extracellular matrix molecules,and adhesion molecules.Additionally,BMSCs release pro-angiogenic factors to promote the formation of new blood vessels.They modulate cytokine expression and regulate macrophage polarization,leading to immunomodulation.Furthermore,BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration,thereby promoting neuronal repair and regeneration.Moreover,this review explores methods of applying BMSCs in PNI treatment,including direct cell trans-plantation into the injured neural tissue,implantation of BMSCs into nerve conduits providing support,and the application of genetically modified BMSCs,among others.These findings confirm the potential of BMSCs in treating PNI.However,with the development of this field,it is crucial to address issues related to BMSC therapy,including establishing standards for extracting,identifying,and cultivating BMSCs,as well as selecting application methods for BMSCs in PNI such as direct transplantation,tissue engineering,and genetic engineering.Addressing these issues will help translate current preclinical research results into clinical practice,providing new and effective treatment strategies for patients with PNI.
基金the Natural Science Foundation of Ministry of Science and Technology of China,No.30230140a grant from Merck Serono (China)
文摘The present study established a chronic experimental autoimmune encephalomyelitis model in C57BL/6 mice induced by myelin oligodendrocyte glycoprotein peptides and complete Freund＇s adjuvant. Onset latency was 12 days, with an incidence rate of 100%. Neuropathological characteristics included perivascular inflammatory cell infiltration, demyelination, neuronal degeneration, and axonal damage within cerebral and myelic white matter. Electron microscopy revealed swollen mitochondria, complete organ disappearance, and fused or broken myelin sheath structure, which were accompanied by myelin sheath reconstruction. Moreover, axonal damage was not consistent with demyelination distribution, and severity of axonal damage did not correlate with demyelination. Results suggested that axonal damage in an experimental autoimmune encephalomyelitis model is not secondary to inflammatory demyelination.
基金Supported by Fondo Sectorial de Investigación para la Educación(FSIE SEP/CONACyT)to MV-T,No.287115Fondo Sectorial de Investigación en Salud y Seguridad Social(FOSISS SS/IMSS/ISSSTE-CONACyT)to BC,No.261459.
文摘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.
基金the National Natural Science Foundation of China, No. 30170311Development Program of Chengdu Military Area Command of Chinese PLA during the Tenth-Five-Year Plan Period, No. 04A007
文摘BACKGROUND： Myelination is a process whereby glial cells identify, adhere, wrap and enclose axons to form a spiral myelin sheath. OBJECTIVE： To investigate the effects of action potential-simulated weak electric fields on myelination in the central nervous system. DESIGN AND SETTING： This single-sample observation study was performed at the 324 Hospital of Chinese PLA. MATERIALS： Two 5 μm carbon fibers were provided by the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. One Sprague Dawley rat, aged 1 day, was used. METHODS： Cerebral cortex was harvested from the rat to prepare a suspension [（1 2）× 10^5/mL] containing neurons and glial cells. To simulate the axon, carbon fibers were placed at the bottom of the neuron-glial cell coculture dish, and were electrified with a single phase square wave current, 1×10^-2, 1×10^-3, 1×10^-4, and 1×10^-5 seconds, 1 Hz, 40 mV, and 10 μA, 30 minutes each, once a day for 10 consecutive days to simulate weak negative electric fields during action potential conduction. MAIN OUTCOME MEASURES： Glial cell growth and wrapping of carbon fibers were observed by phase contrast microscopy and immunohistochemistry. RESULTS： On culture day 7, cell groups were found to adhere to negative carbon fibers in the 1 × 10^-3 seconds square wave group. Cell membrane-like substances grew out of cell groups, wrapped the carbon fibers, and stretched to the ends of carbon fibers. Only some small and round cells close to negative carbon fibers were found on culture day 12. In the 1 × 10^-4 and 1 × 10^-3 seconds square wave groups, the negative carbon fibers were wrapped by oligodendrocytes or their progenitor cells. CONCLUSION： The local negative electric field which is generated by action potentials at 1×（10^-4-10^-3） seconds, 40 mV can directly initiate and participate in myelination in the central nervous system.
基金supported by the Natural Science Foundation of Jiangsu Province of China,No.BK20171180(to XRW)
文摘Rosmarinic acid,a common ester extracted from Rosemary,Perilla frutescens,and Salvia miltiorrhiza Bunge,has been shown to have protective effects against various diseases.This is an investigation into whether rosmarinic acid can also affect the changes of white matter fibers and cognitive deficits caused by hypoxic injury.The right common carotid artery of 3-day-old rats was ligated for 2 hours.The rats were then prewarmed in a plastic container with holes in the lid,which was placed in 37°C water bath for 30 minutes.Afterwards,the rats were exposed to an atmosphere with 8% O2 and 92% N2 for 30 minutes to establish the perinatal hypoxia/ischemia injury models.The rat models were intraperitoneally injected with rosmarinic acid 20 mg/kg for 5 consecutive days.At 22 days after birth,rosmarinic acid was found to improve motor,anxiety,learning and spatial memory impairments induced by hypoxia/ischemia injury.Furthermore,rosmarinic acid promoted the proliferation of oligodendrocyte progenitor cells in the subventricular zone.After hypoxia/ischemia injury,rosmarinic acid reversed to some extent the downregulation of myelin basic protein and the loss of myelin sheath in the corpus callosum of white matter structure.Rosmarinic acid partially slowed down the expression of oligodendrocyte marker Olig2 and myelin basic protein and the increase of oligodendrocyte apoptosis marker inhibitors of DNA binding 2.These data indicate that rosmarinic acid ameliorated the cognitive dysfunction after perinatal hypoxia/ischemia injury by improving remyelination in corpus callosum.This study was approved by the Animal Experimental Ethics Committee of Xuzhou Medical University,China (approval No.20161636721) on September 16,2017.
基金supported by Talent Foundation of the Affiliated Hospital of Luzhou Medical College, No. 09057Youth Researcher Foundation of Luzhou Medical College, No. 09013+2 种基金Key Program of the Education Department of Sichuan Province, No. 09ZA046Scientific Research Foundation of the Health Department of Sichuan Province, No. 090231a grant from Science and Technology Bureau of Luzhou, No. (2009)1
文摘An animal model of cortical dysplasia was established through X-ray irradiation induced subcortical heterotopic nodules in rats. Transmission electron microscopy detection of the ultrastructure and the stereology examination showed that there was a significant decrease in cerebral white matter and hippocampal volume, the total volume, volume density, length density and total length of the myelinated fibers in the white matter of cortical dysplasia rats. Subcortical heterotopic nodules of the hippocampal CA1 region and synaptic number density in the CA3 region were reduced compared with normal rats. Our experimental findings indicate that erosed subcortical heterotopic nodules, decreased total length of myelinated nerve fibers and demyelination directly lead to a reduction of white matter volume.
