MicroRNAs play important roles in post-transcriptional regulation of gene expression by inhibiting protein translation and/or promoting mRNA degradation.Importantly,biogenesis of microRNAs displays specific temporal a...MicroRNAs play important roles in post-transcriptional regulation of gene expression by inhibiting protein translation and/or promoting mRNA degradation.Importantly,biogenesis of microRNAs displays specific temporal and spatial profiles in distinct cell and tissue types and hence affects a broad spectrum of biological functions in normal cell growth and tumor development.Recent discoveries have revealed sophisticated mechanisms that control microRNA production and homeostasis in response to developmental and extracellular signals.Moreover,a link between dysregulation of microRNAs and human brain disorders has become increasingly evident.In this review,we focus on recent advances in understanding the regulation of microRNA biogenesis and function in neuronal and glial development in the mammalian brain,and dysregulation of the microRNA pathway in neurodevelopmental and neurodegenerative diseases.展开更多
MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which ...MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which may enhance axonal remyelination after nerve injuries in the central nervous system(CNS).As such,the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation,maturation and myelination could be a promising approach for nerve repair.However,nerve injuries in the CNS also involve other cell types,such as microglia and astrocytes.Herein,we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo.We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation.In addition,we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro.Collectively,our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries.All experimental procedures were approved by the Institutional Animal Care and Use Committee(IACUC),Nanyang Technological University(approval No.A0309 and A0333)on April 27,2016 and October 8,2016.展开更多
Posttraumatic stress disorder(PTSD)is a complex mental disorder notable for traumatic experience memory.Although current first-line treatments are linked with clinically important symptom reduction,a large proportion ...Posttraumatic stress disorder(PTSD)is a complex mental disorder notable for traumatic experience memory.Although current first-line treatments are linked with clinically important symptom reduction,a large proportion of patients retained to experience considerable residual symptoms,indicating pathogenic mechanism should be illustrated further.Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation.However,its role in PTSD remains to be elucidated.In this study,we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus.Fluoxetine,but not risperidone or sertraline,has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities.Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling.Our data demonstrated the correlation between PTSD and abnormal myelination,suggesting that the oligodendroglial lineage could be a target for PTSD treatment.展开更多
Directional axon regeneration and remyelination are crucial for repair of spinal cord injury(SCI),but existing treatments do not effectively promote those processes.Here,we propose a strategy for construction of niche...Directional axon regeneration and remyelination are crucial for repair of spinal cord injury(SCI),but existing treatments do not effectively promote those processes.Here,we propose a strategy for construction of niche-specific spinal white matter-like tissue(WMLT)using decellularized optic nerve(DON)loaded with neurotrophin-3(NT-3)-overexpressing oligodendrocyte precursor cells.A rat model with a white matter defect in the dorsal spinal cord of the T10 segment was used.The WMLT transplantation group showed significant improvement in coordinated motor functions compared with the control groups.WMLT transplants integrated well with host spinal cord white matter,effectively addressing several barriers to directional axonal regeneration and myelination during SCI repair.In WMLT,laminin was found to promote development of oligodendroglial lineage(OL)cells by binding to laminin receptors.Interestingly,laminin could also guide linear axon regeneration via interactions with specific integrins on the axon surface.The WMLT developed here utilizes the unique microstructure and bioactive matrix of DON to create a niche rich in laminin,NT-3 and OL cells to achieve significant structural repair of SCI.Our protocol can help to promote research on repair of nerve injury and construction of neural tissues and organoids that form specific cell niches.展开更多
Objective Nogo-A is an axon regeneration inhibitor, and its function in central nervous system （CNS） is still unknown. The present study is to explore the relationship between the expression of Nogo-A and the malign...Objective Nogo-A is an axon regeneration inhibitor, and its function in central nervous system （CNS） is still unknown. The present study is to explore the relationship between the expression of Nogo-A and the malignancy of oligodendroglial tumors in patients. Methods Tumor tissue samples with different malignancy grade were obtained from the hospitals. The samples used for detection had been diagnosed as oligodendroglial tumors （oligodendroglioma or anaplastic oligodendroglioma）. The expression of Nogo-A was detected by irmnunohistochemistry and western-blot analysis. The correlation test between the Nogo-A expression and the morphological changes （the percentages of atypical cells and mitotic cells in the tumors） related to the malignancy of tumor tissues was performed. Results There was significant negative correlation between the Nogo-A expression and the morphological change of tumor tissues according to immunohistochemistry. Western-blot analysis also indicated that the gray value of Nogo-A protein band in the oligo- dendroglioma group was significantly higher than that in the anaplastic oligodendroglioma group. Conclusion Nogo-A expression was negatively correlated with the malignancy grade of oligodendroglial tumors.展开更多
文摘MicroRNAs play important roles in post-transcriptional regulation of gene expression by inhibiting protein translation and/or promoting mRNA degradation.Importantly,biogenesis of microRNAs displays specific temporal and spatial profiles in distinct cell and tissue types and hence affects a broad spectrum of biological functions in normal cell growth and tumor development.Recent discoveries have revealed sophisticated mechanisms that control microRNA production and homeostasis in response to developmental and extracellular signals.Moreover,a link between dysregulation of microRNAs and human brain disorders has become increasingly evident.In this review,we focus on recent advances in understanding the regulation of microRNA biogenesis and function in neuronal and glial development in the mammalian brain,and dysregulation of the microRNA pathway in neurodevelopmental and neurodegenerative diseases.
基金supported by the Singapore National Research Foundation under its NMRC-CBRG grants(Project award number:NMRC/CBRG/0096/2015) and administered by the Singapore Ministry of Health’s National Medical Research Councilpartially supported by the MOE Academic Research Funding(AcRF) Tier 1 grant(RG148/14) and Tier 2 grant(MOE2015-T2-1-023)
文摘MiR-219 and miR-338(miR-219/miR-338)are oligodendrocyte-specific microRNAs.The overexpression of these miRs in oligodendrocyte precursor cells promotes their differentiation and maturation into oligodendrocytes,which may enhance axonal remyelination after nerve injuries in the central nervous system(CNS).As such,the delivery of miR-219/miR-338 to the CNS to promote oligodendrocyte precursor cell differentiation,maturation and myelination could be a promising approach for nerve repair.However,nerve injuries in the CNS also involve other cell types,such as microglia and astrocytes.Herein,we investigated the effects of miR-219/miR-338 treatment on microglia and astrocytes in vitro and in vivo.We found that miR-219/miR-338 diminished microglial expression of pro-inflammatory cytokines and suppressed astrocyte activation.In addition,we showed that miR-219/miR-338 enhanced oligodendrocyte precursor cell differentiation and maturation in a scratch assay paradigm that re-created a nerve injury condition in vitro.Collectively,our results suggest miR-219/miR-338 as a promising treatment for axonal remyelination in the CNS following nerve injuries.All experimental procedures were approved by the Institutional Animal Care and Use Committee(IACUC),Nanyang Technological University(approval No.A0309 and A0333)on April 27,2016 and October 8,2016.
基金supported by grants from the National Nature Science Foundation of China(32271034,32070964,82301703,32300791,and 81901378)Science and Technology Innovation Enhancement Project of Army Medical University(2022XQN40)+4 种基金National Key Research and Development Program of China(2021ZD0201703)Chongqing Natural Science Fund for Distinguished Young Scholars(CSTB2023NSCQ-JQX0030)Undergraduate Research Cultivation Project of Army Medical University(2020XBK16)Guangdong Basic and Applied Basic Research Foundation(2021A1515110268 and 2023A1515010651)Shenzhen Fundamental Research Program(RCBS20210706092411028 and JCYJ20210324121214039).
文摘Posttraumatic stress disorder(PTSD)is a complex mental disorder notable for traumatic experience memory.Although current first-line treatments are linked with clinically important symptom reduction,a large proportion of patients retained to experience considerable residual symptoms,indicating pathogenic mechanism should be illustrated further.Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation.However,its role in PTSD remains to be elucidated.In this study,we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus.Fluoxetine,but not risperidone or sertraline,has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities.Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling.Our data demonstrated the correlation between PTSD and abnormal myelination,suggesting that the oligodendroglial lineage could be a target for PTSD treatment.
基金supported by grants from the National Natural Science Foundation of China,Nos.81891003(to YSZ),81971157(to BQL)the National Key R&D Program of China,Nos.2017YFA0104704(to BQL),2017YFA0104701(to YSZ)+5 种基金the Young Elite Scientist Sponsorship Program by CAST(YESS),No.2018QNRC001(to BQL)the Fundamental Research Funds for the Central Universities,China,Nos.20ykpy156(to YHM)the 111 Project for Academic Exchange Program,China,No.B13037(to YSZ,YD and YHM)the Natural Science Foundation of Guangdong Province,China,Nos.2018A030310110(to YHM),2020A1515011537(to YHM)the Foundation of Guangdong Province,China,No.2017B020210012(to YSZ and XZ)the Start-up Foundation of Guangdong Province,China,No.2018A030310113(to GL).
文摘Directional axon regeneration and remyelination are crucial for repair of spinal cord injury(SCI),but existing treatments do not effectively promote those processes.Here,we propose a strategy for construction of niche-specific spinal white matter-like tissue(WMLT)using decellularized optic nerve(DON)loaded with neurotrophin-3(NT-3)-overexpressing oligodendrocyte precursor cells.A rat model with a white matter defect in the dorsal spinal cord of the T10 segment was used.The WMLT transplantation group showed significant improvement in coordinated motor functions compared with the control groups.WMLT transplants integrated well with host spinal cord white matter,effectively addressing several barriers to directional axonal regeneration and myelination during SCI repair.In WMLT,laminin was found to promote development of oligodendroglial lineage(OL)cells by binding to laminin receptors.Interestingly,laminin could also guide linear axon regeneration via interactions with specific integrins on the axon surface.The WMLT developed here utilizes the unique microstructure and bioactive matrix of DON to create a niche rich in laminin,NT-3 and OL cells to achieve significant structural repair of SCI.Our protocol can help to promote research on repair of nerve injury and construction of neural tissues and organoids that form specific cell niches.
基金This work was supported by grants from the National Nature Science Foundation of China （No. 30471775）the Project of Science and Technology of Hubci Province （No. 2005AA301C15）.
文摘Objective Nogo-A is an axon regeneration inhibitor, and its function in central nervous system （CNS） is still unknown. The present study is to explore the relationship between the expression of Nogo-A and the malignancy of oligodendroglial tumors in patients. Methods Tumor tissue samples with different malignancy grade were obtained from the hospitals. The samples used for detection had been diagnosed as oligodendroglial tumors （oligodendroglioma or anaplastic oligodendroglioma）. The expression of Nogo-A was detected by irmnunohistochemistry and western-blot analysis. The correlation test between the Nogo-A expression and the morphological changes （the percentages of atypical cells and mitotic cells in the tumors） related to the malignancy of tumor tissues was performed. Results There was significant negative correlation between the Nogo-A expression and the morphological change of tumor tissues according to immunohistochemistry. Western-blot analysis also indicated that the gray value of Nogo-A protein band in the oligo- dendroglioma group was significantly higher than that in the anaplastic oligodendroglioma group. Conclusion Nogo-A expression was negatively correlated with the malignancy grade of oligodendroglial tumors.
