Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord...Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.展开更多
Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells ...Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells towards the neuronal state is achieved due to sophisticated mechanisms of epigenetic,transcriptional,and post-transcriptional regulation.Understanding these neurogenic mechanisms is of major importance,not only for shedding light on very complex and crucial developmental processes,but also for the identification of putative reprogramming factors,that harbor hierarchically central regulatory roles in the course of neurogenesis and bare thus the capacity to drive direct reprogramming towards the neuronal fate.The major transcriptional programs that orchestrate the neurogenic process have been the focus of research for many years and key neurogenic transcription factors,as well as repressor complexes,have been identified and employed in direct reprogramming protocols to convert non-neuronal cells,into functional neurons.The post-transcriptional regulation of gene expression during nervous system development has emerged as another important and intricate regulatory layer,strongly contributing to the complexity of the mechanisms controlling neurogenesis and neuronal function.In particular,recent advances are highlighting the importance of specific RNA binding proteins that control major steps of mRNA life cycle during neurogenesis,such as alternative splicing,polyadenylation,stability,and translation.Apart from the RNA binding proteins,microRNAs,a class of small non-coding RNAs that block the translation of their target mRNAs,have also been shown to play crucial roles in all the stages of the neurogenic process,from neural stem/progenitor cell proliferation,neuronal differentiation and migration,to functional maturation.Here,we provide an overview of the most prominent post-transcriptional mechanisms mediated by RNA binding proteins and microRNAs during the neurogenic process,giving particular emphasis on展开更多
流行性乙型脑炎(epidemic encephalitis type B,简称乙脑)是由乙型脑炎病毒(encephalitis B virus,简称乙脑病毒)感染引起的中枢神经系统疾病。乙脑病毒感染具有明显的嗜神经性,它在神经元细胞中大量增殖并造成其损伤,以干扰素(interfer...流行性乙型脑炎(epidemic encephalitis type B,简称乙脑)是由乙型脑炎病毒(encephalitis B virus,简称乙脑病毒)感染引起的中枢神经系统疾病。乙脑病毒感染具有明显的嗜神经性,它在神经元细胞中大量增殖并造成其损伤,以干扰素(interferons,IFNs)为核心的固有免疫应答在机体抵御乙脑病毒感染的过程中发挥重要作用。多项研究表明,乙脑病毒感染神经元细胞后,宿主细胞模式识别受体可识别病毒的结构成分,并经接头分子和转录因子等信号传递,介导IFN的产生。IFN随后激活下游干扰素信号通路,转录多种干扰素诱导基因(interferon stimulated genes,ISGs),启动宿主对病毒的固有免疫应答反应。现就乙脑病毒感染神经元细胞的固有免疫相关分子,如模式识别分子、关键接头分子、转录因子及IFN信号转导过程中相关的调控分子作一概述。展开更多
Dioxin can cause a series of neural toxicological effects. Micro RNAs（mi Rs） play important roles in regulating nervous system function and mediating cellular responses to environmental pollutants, such as dioxin. H...Dioxin can cause a series of neural toxicological effects. Micro RNAs（mi Rs） play important roles in regulating nervous system function and mediating cellular responses to environmental pollutants, such as dioxin. Hsa-mi R-146 b-5 p appears to be involved in neurodegenerative diseases and brain tumors. However, little is known about effects of dioxin on the expression of hsa-mi R-146 b-5 p. We found that the hsa-mi R-146 b-5 p expression and its promoter activity were significantly increased in dioxin treated SK-N-SH cells, a human-derived neuroblastoma cell line. Potential roles of hsa-mi R-146 b-5 p in mediating neural toxicological effects of dioxin may be due to the regulation of certain target genes. We further confirmed that hsa-mi R-146 b-5 p significantly suppressed acetylcholinesterase（ACh E） activity and targeted the3′-untranslated region of the ACh E T subunit, which has been down-regulated in dioxin treated SK-N-SH cells. Functional bioinformatic analysis showed that the known and predicted target genes of hsa-mi R-146 b-5 p were involved in some brain functions or cyto-toxicities related to known dioxin effects, including synapse transmission, in which ACh E may serve as a responsive gene for mediating the effect.展开更多
针对电网三相对称故障条件下风电场电压不稳定的问题,文章提出了一种基于神经元的风储联合系统无功功率自适应控制策略,该策略以风储联合系统公共耦合点(Point of Common Coupling,PCC)的电压和电流为控制器的输入,采用Hebb学习算法作...针对电网三相对称故障条件下风电场电压不稳定的问题,文章提出了一种基于神经元的风储联合系统无功功率自适应控制策略,该策略以风储联合系统公共耦合点(Point of Common Coupling,PCC)的电压和电流为控制器的输入,采用Hebb学习算法作为自适应律,以获得准确的无功补偿。通过动态调整控制器的参数,使储能系统协调风电达到自适应输出无功功率的效果,提高系统在电网故障下的电压稳定性和风电故障穿越能力。最后,利用Matlab/Simulink仿真验证了该控制策略的有效性和正确性,与常规PI控制策略相比,文章所提出的控制策略可使风储系统迅速提供无功功率,PCC点的电压得到明显上升。展开更多
The glycemia-sensitive neuron in lateral hypothalamic area (LHA) is one of the important central neural events involved in the feeding control. Electrophysio-logical studies have demonstrated that gastrointestinal vag...The glycemia-sensitive neuron in lateral hypothalamic area (LHA) is one of the important central neural events involved in the feeding control. Electrophysio-logical studies have demonstrated that gastrointestinal vagal afferent inputs could convey the meal-related information of gastrointestinal tract to the hypothalamus. In this study, we examined whether the gastric vagal afferent inputs could reach the glycemia-sensitive neurons of the LHA by using in vivo extracellular recording technique in the rat. The results showed that stimulation of gastric vagal nerves elicited two types of the LHA neurons responses: the phasic response (93/116, 80.2%) and the change in cells firing pattern (23/116, 19.8%). Within the 93 cells that responded to the gastric vagal stimulation with a phasic response, 67 (72.0%) showed an inhibition in the cells firing rate, 26 (27.4%) were excited. Of the 23 cells that showed a change in the firing pattern, 13 responded to the gastric vagal stimulation with a long-lasting increase or decrease in firing rate, the remaining 10 cells turned their discrete spiking to the burst discharging. In addition, of 101 LHA neurons including the two types of responsive neurons, 73 (72.3%) were identified to be glyce-mia-sensitive neurons. These results demonstrated that the gastric vagal afferent inputs could reach the LHA and pre-dominantly reach those glycemia-sensitive neurons in the LHA. Presumably, the modulation of glycemia-sensitive neurons of LHA by the gastric vagal afferent inputs may play an important role in the short-term regulation of feed-ing behavior.展开更多
基金supported by Guangdong Provincial Basic and Applied Basic Research Fund,No.2021A1515011299(to KT)。
文摘Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.
基金supported by Stavros Niarhos FoundationGreek‘Flagship Action for the Study of Neurodegenerative Diseases on the Basis of Precision Medicine’(to DT).
文摘Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells towards the neuronal state is achieved due to sophisticated mechanisms of epigenetic,transcriptional,and post-transcriptional regulation.Understanding these neurogenic mechanisms is of major importance,not only for shedding light on very complex and crucial developmental processes,but also for the identification of putative reprogramming factors,that harbor hierarchically central regulatory roles in the course of neurogenesis and bare thus the capacity to drive direct reprogramming towards the neuronal fate.The major transcriptional programs that orchestrate the neurogenic process have been the focus of research for many years and key neurogenic transcription factors,as well as repressor complexes,have been identified and employed in direct reprogramming protocols to convert non-neuronal cells,into functional neurons.The post-transcriptional regulation of gene expression during nervous system development has emerged as another important and intricate regulatory layer,strongly contributing to the complexity of the mechanisms controlling neurogenesis and neuronal function.In particular,recent advances are highlighting the importance of specific RNA binding proteins that control major steps of mRNA life cycle during neurogenesis,such as alternative splicing,polyadenylation,stability,and translation.Apart from the RNA binding proteins,microRNAs,a class of small non-coding RNAs that block the translation of their target mRNAs,have also been shown to play crucial roles in all the stages of the neurogenic process,from neural stem/progenitor cell proliferation,neuronal differentiation and migration,to functional maturation.Here,we provide an overview of the most prominent post-transcriptional mechanisms mediated by RNA binding proteins and microRNAs during the neurogenic process,giving particular emphasis on
文摘流行性乙型脑炎(epidemic encephalitis type B,简称乙脑)是由乙型脑炎病毒(encephalitis B virus,简称乙脑病毒)感染引起的中枢神经系统疾病。乙脑病毒感染具有明显的嗜神经性,它在神经元细胞中大量增殖并造成其损伤,以干扰素(interferons,IFNs)为核心的固有免疫应答在机体抵御乙脑病毒感染的过程中发挥重要作用。多项研究表明,乙脑病毒感染神经元细胞后,宿主细胞模式识别受体可识别病毒的结构成分,并经接头分子和转录因子等信号传递,介导IFN的产生。IFN随后激活下游干扰素信号通路,转录多种干扰素诱导基因(interferon stimulated genes,ISGs),启动宿主对病毒的固有免疫应答反应。现就乙脑病毒感染神经元细胞的固有免疫相关分子,如模式识别分子、关键接头分子、转录因子及IFN信号转导过程中相关的调控分子作一概述。
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Nos.XDB14030401,XDB14030402)the National Natural Science Foundation of China(Nos.21177150,21377160,21525730)
文摘Dioxin can cause a series of neural toxicological effects. Micro RNAs（mi Rs） play important roles in regulating nervous system function and mediating cellular responses to environmental pollutants, such as dioxin. Hsa-mi R-146 b-5 p appears to be involved in neurodegenerative diseases and brain tumors. However, little is known about effects of dioxin on the expression of hsa-mi R-146 b-5 p. We found that the hsa-mi R-146 b-5 p expression and its promoter activity were significantly increased in dioxin treated SK-N-SH cells, a human-derived neuroblastoma cell line. Potential roles of hsa-mi R-146 b-5 p in mediating neural toxicological effects of dioxin may be due to the regulation of certain target genes. We further confirmed that hsa-mi R-146 b-5 p significantly suppressed acetylcholinesterase（ACh E） activity and targeted the3′-untranslated region of the ACh E T subunit, which has been down-regulated in dioxin treated SK-N-SH cells. Functional bioinformatic analysis showed that the known and predicted target genes of hsa-mi R-146 b-5 p were involved in some brain functions or cyto-toxicities related to known dioxin effects, including synapse transmission, in which ACh E may serve as a responsive gene for mediating the effect.
文摘针对电网三相对称故障条件下风电场电压不稳定的问题,文章提出了一种基于神经元的风储联合系统无功功率自适应控制策略,该策略以风储联合系统公共耦合点(Point of Common Coupling,PCC)的电压和电流为控制器的输入,采用Hebb学习算法作为自适应律,以获得准确的无功补偿。通过动态调整控制器的参数,使储能系统协调风电达到自适应输出无功功率的效果,提高系统在电网故障下的电压稳定性和风电故障穿越能力。最后,利用Matlab/Simulink仿真验证了该控制策略的有效性和正确性,与常规PI控制策略相比,文章所提出的控制策略可使风储系统迅速提供无功功率,PCC点的电压得到明显上升。
文摘The glycemia-sensitive neuron in lateral hypothalamic area (LHA) is one of the important central neural events involved in the feeding control. Electrophysio-logical studies have demonstrated that gastrointestinal vagal afferent inputs could convey the meal-related information of gastrointestinal tract to the hypothalamus. In this study, we examined whether the gastric vagal afferent inputs could reach the glycemia-sensitive neurons of the LHA by using in vivo extracellular recording technique in the rat. The results showed that stimulation of gastric vagal nerves elicited two types of the LHA neurons responses: the phasic response (93/116, 80.2%) and the change in cells firing pattern (23/116, 19.8%). Within the 93 cells that responded to the gastric vagal stimulation with a phasic response, 67 (72.0%) showed an inhibition in the cells firing rate, 26 (27.4%) were excited. Of the 23 cells that showed a change in the firing pattern, 13 responded to the gastric vagal stimulation with a long-lasting increase or decrease in firing rate, the remaining 10 cells turned their discrete spiking to the burst discharging. In addition, of 101 LHA neurons including the two types of responsive neurons, 73 (72.3%) were identified to be glyce-mia-sensitive neurons. These results demonstrated that the gastric vagal afferent inputs could reach the LHA and pre-dominantly reach those glycemia-sensitive neurons in the LHA. Presumably, the modulation of glycemia-sensitive neurons of LHA by the gastric vagal afferent inputs may play an important role in the short-term regulation of feed-ing behavior.
