A new technology called in vivo glia-to-neuron conversion has emerged in recent years as a promising next generation therapy for neural regeneration and repair. This is achieved through reprogramming endogenous glial ...A new technology called in vivo glia-to-neuron conversion has emerged in recent years as a promising next generation therapy for neural regeneration and repair. This is achieved through reprogramming endogenous glial cells into neurons in the central nervous system through ectopically expressing neural transcriptional factors in glial cells. Previous studies have been focusing on glial cells in the grey matter such as the cortex and striatum, but whether glial cells in the white matter can be reprogrammed or not is unknown. To address this fundamental question, we express NeuroD1 in the astrocytes of both grey matter(cortex and striatum) and white matter(corpus callosum) to investigate the conversion efficiency, neuronal subtypes, and electrophysiological features of the converted neurons. We discover that NeuroD1 can efficiently reprogram the astrocytes in the grey matter into functional neurons, but the astrocytes in the white matter are much resistant to neuronal reprogramming. The converted neurons from cortical and striatal astrocytes are composed of both glutamatergic and GABAergic neurons, capable of firing action potentials and having spontaneous synaptic activities. In contrast, the few astrocyte-converted neurons in the white matter are rather immature with rare synaptic events. These results provide novel insights into the differential reprogramming capability between the astrocytes in the grey matter versus the white matter, and highlight the impact of regional astrocytes as well as microenvironment on the outcome of glia-toneuron conversion. Since human brain has large volume of white matter, this study will provide important guidance for future development of in vivo glia-to-neuron conversion technology into potential clinical therapies. Experimental protocols in this study were approved by the Laboratory Animal Ethics Committee of Jinan University(approval No. IACUC-20180321-03) on March 21, 2018.展开更多
目的探讨伴胼胝体压部可逆性病变的轻度脑炎／脑病（ mild encephalitis/encephalopathy with a reversible splenial lesion ,MERS）的临床表现及影像学特点。方法对11例诊断为MERS患者的临床及影像学资料进行回顾性分析，其中成人4例...目的探讨伴胼胝体压部可逆性病变的轻度脑炎／脑病（ mild encephalitis/encephalopathy with a reversible splenial lesion ,MERS）的临床表现及影像学特点。方法对11例诊断为MERS患者的临床及影像学资料进行回顾性分析，其中成人4例，青少年及儿童7例，总结其临床及影像学特点。结果11例MERS患者均有前驱感染史。脑炎／脑病症状表现为头痛伴嗜睡6例、意识模糊3例、癫痫2例、幻视2例、谵妄1例。11例患者症状均于2周内明显缓解。影像学检查11例均表现为孤立性胼胝体压部病变，其中9例表现为胼胝体压部中央部类圆形异常信号，2例为累及整个胼胝体压部的弧形异常信号；病灶于T2WI、弥散加权成像（DWU均呈高信号并伴表观弥散系数（ADC）明显减低；复查MRI病灶均于4周内消失。结论MERS起病前多有前驱感染史，临床表现为头痛、意识障碍、癫痫、幻视等神经系统症状。影像学上多表现为MRI上胼胝体压部类圆形或弧形病灶，DWI呈高信号伴ADC图降低。MERS预后良好。部分患者MRI上病灶的出现可滞后于脑病症状。展开更多
基金supported in part by the National Natural Science Foundation of China(Grant No.31701291 to WL,U1801681 to GC)the China Postdoctoral Science Foundation(Grant No.2016M602600 to WL)+1 种基金the Guangdong Grant ‘Key Technologies for Treatment of Brain Disorders’(Grant No.2018B030332001 to GC)the Internal Funding of Jinan University,China(Grant No.21616110 to GC)
文摘A new technology called in vivo glia-to-neuron conversion has emerged in recent years as a promising next generation therapy for neural regeneration and repair. This is achieved through reprogramming endogenous glial cells into neurons in the central nervous system through ectopically expressing neural transcriptional factors in glial cells. Previous studies have been focusing on glial cells in the grey matter such as the cortex and striatum, but whether glial cells in the white matter can be reprogrammed or not is unknown. To address this fundamental question, we express NeuroD1 in the astrocytes of both grey matter(cortex and striatum) and white matter(corpus callosum) to investigate the conversion efficiency, neuronal subtypes, and electrophysiological features of the converted neurons. We discover that NeuroD1 can efficiently reprogram the astrocytes in the grey matter into functional neurons, but the astrocytes in the white matter are much resistant to neuronal reprogramming. The converted neurons from cortical and striatal astrocytes are composed of both glutamatergic and GABAergic neurons, capable of firing action potentials and having spontaneous synaptic activities. In contrast, the few astrocyte-converted neurons in the white matter are rather immature with rare synaptic events. These results provide novel insights into the differential reprogramming capability between the astrocytes in the grey matter versus the white matter, and highlight the impact of regional astrocytes as well as microenvironment on the outcome of glia-toneuron conversion. Since human brain has large volume of white matter, this study will provide important guidance for future development of in vivo glia-to-neuron conversion technology into potential clinical therapies. Experimental protocols in this study were approved by the Laboratory Animal Ethics Committee of Jinan University(approval No. IACUC-20180321-03) on March 21, 2018.
文摘目的探讨伴胼胝体压部可逆性病变的轻度脑炎／脑病（ mild encephalitis/encephalopathy with a reversible splenial lesion ,MERS）的临床表现及影像学特点。方法对11例诊断为MERS患者的临床及影像学资料进行回顾性分析，其中成人4例，青少年及儿童7例，总结其临床及影像学特点。结果11例MERS患者均有前驱感染史。脑炎／脑病症状表现为头痛伴嗜睡6例、意识模糊3例、癫痫2例、幻视2例、谵妄1例。11例患者症状均于2周内明显缓解。影像学检查11例均表现为孤立性胼胝体压部病变，其中9例表现为胼胝体压部中央部类圆形异常信号，2例为累及整个胼胝体压部的弧形异常信号；病灶于T2WI、弥散加权成像（DWU均呈高信号并伴表观弥散系数（ADC）明显减低；复查MRI病灶均于4周内消失。结论MERS起病前多有前驱感染史，临床表现为头痛、意识障碍、癫痫、幻视等神经系统症状。影像学上多表现为MRI上胼胝体压部类圆形或弧形病灶，DWI呈高信号伴ADC图降低。MERS预后良好。部分患者MRI上病灶的出现可滞后于脑病症状。
