Astrocytes(ASTs)and oligodendroglial lineage cells(OLGs)are major macroglial cells in the central nervous system.ASTs communicate with each other through connexin(Cx)and Cx-based network structures,both of which allow...Astrocytes(ASTs)and oligodendroglial lineage cells(OLGs)are major macroglial cells in the central nervous system.ASTs communicate with each other through connexin(Cx)and Cx-based network structures,both of which allow for quick transport of nutrients and signals.Moreover,ASTs interact with OLGs through connexin(Cx)-mediated networks to modulate various physiological processes in the brain.In this article,following a brief description of the infrastructural basis of the glial networks and exocrine factors by which ASTs and OLGs may crosstalk,we focus on recapitulating how the interactions between these two types of glial cells modulate myelination,and how the AST-OLG interactions are involved in protecting the integrity of the blood-brain barrier(BBB)and regulating synaptogenesis and neural activity.Recent studies further suggest that AST-OLG interactions are associated with myelin-related diseases,such as multiple sclerosis.A better understanding of the regulatory mechanisms underlying AST-OLG interactions may inspire the development of novel therapeutic strategies for related brain diseases.展开更多
Myelination by oligodendroglial cells （OLs） enables the propagation of action potentials along neuronal axons, which is essential for rapid information flow in the central nervous system. Besides saltatory conductio...Myelination by oligodendroglial cells （OLs） enables the propagation of action potentials along neuronal axons, which is essential for rapid information flow in the central nervous system. Besides saltatory conduction, the myelin sheath also protects axons against inflammatory and oxidative insults. Loss of myelin results in axonal damage and ultimately neuronal loss in demyelinating disorders. However, accumulating evidence indicates that OLs also provide support to neurons via mechanisms beyond the insulating function of myelin. More im- portantly, an increasing volume of reports indicates defects of OLs in numerous neurodegenerative diseases, sometimes even preceding neuronal loss in pre-symptomatic episodes, suggesting that OL pathology may be an important mechanism contributing to the initiation and/or progression of neurodegeneration. This review fo- cuses on the emerging picture of neuronal support by OLs in the pathogenesis of neurodegenerative disorders through diverse molecular and cellular mechanisms, including direct neuron-myelin interaction, metabolic sup- port by OLs, and neurotrophic factors produced by and/or acting on OLs.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
基金supported by the Ministry of Science and Technology of China(2021ZD0201700)the National Natural Science Foundation of China(31921003).
文摘Astrocytes(ASTs)and oligodendroglial lineage cells(OLGs)are major macroglial cells in the central nervous system.ASTs communicate with each other through connexin(Cx)and Cx-based network structures,both of which allow for quick transport of nutrients and signals.Moreover,ASTs interact with OLGs through connexin(Cx)-mediated networks to modulate various physiological processes in the brain.In this article,following a brief description of the infrastructural basis of the glial networks and exocrine factors by which ASTs and OLGs may crosstalk,we focus on recapitulating how the interactions between these two types of glial cells modulate myelination,and how the AST-OLG interactions are involved in protecting the integrity of the blood-brain barrier(BBB)and regulating synaptogenesis and neural activity.Recent studies further suggest that AST-OLG interactions are associated with myelin-related diseases,such as multiple sclerosis.A better understanding of the regulatory mechanisms underlying AST-OLG interactions may inspire the development of novel therapeutic strategies for related brain diseases.
基金supported by NIH grants NS070526 and NS056097 to YF,and NS070526-01A1S1 to MDMANB and MDM were supported by NIH training grant T32GM008602
文摘Myelination by oligodendroglial cells （OLs） enables the propagation of action potentials along neuronal axons, which is essential for rapid information flow in the central nervous system. Besides saltatory conduction, the myelin sheath also protects axons against inflammatory and oxidative insults. Loss of myelin results in axonal damage and ultimately neuronal loss in demyelinating disorders. However, accumulating evidence indicates that OLs also provide support to neurons via mechanisms beyond the insulating function of myelin. More im- portantly, an increasing volume of reports indicates defects of OLs in numerous neurodegenerative diseases, sometimes even preceding neuronal loss in pre-symptomatic episodes, suggesting that OL pathology may be an important mechanism contributing to the initiation and/or progression of neurodegeneration. This review fo- cuses on the emerging picture of neuronal support by OLs in the pathogenesis of neurodegenerative disorders through diverse molecular and cellular mechanisms, including direct neuron-myelin interaction, metabolic sup- port by OLs, and neurotrophic factors produced by and/or acting on OLs.
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.
