Sex differences in microRNA regulation of gene expression: no smoke, just miRs

Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on sexually dimorphic neural populations within the central nervous system. This review will examine an alternative explanation by describing what is known about the role of peripheral structures and mechanisms (both neural and non-neural) in producing sex differences in the central nervous system. The focus of the review will be on experimental evidence obtained from studies of androgenic masculinization of the spinal nucleus of the bulbocavernosus, but other systems will also be considered.     

Neural progenitor diversity and their therapeutic potential for spinal cord repair

Development of the central nervous system (CNS) requires progressive differentiation of neural stem cells, which generate a variety of neural progenitors with distinct properties and differentiation potentials in a spatiotemporally restricted manner. The underlying mechanisms of neural progenitor diversification during development started to be unraveled over the past years. We have addressed these questions by v-myc immortalization method and generation of neural progenitor clones. These clones are served as in vitro models of neural differentiation and cellular tools for transplantation in animal models of neurological disorders including spinal cord injury. In this review, we will discuss features of two neural progenitor types (radial glia and GABAergic interneuron progenitor) and diversification even within each progenitor type. We will also discuss pathophysiology of spinal cord injury and our ongoing research to address both motor and sensory malfunctions by transplantation of these neural progenitors.     

Epigenetics in the nervous system: An overview of its essential role

The role that epigenetic mechanisms play in phenomena such as cellular differentiation during embryonic development, X chromosome inactivation, and cancers is well-characterized. Epigenetic mechanisms have been implicated to be the mediators of several functions in the nervous system such as in neuronal-glial differentiation, adult neurogenesis, the modulation of neural behavior and neural plasticity, and also in higher brain functions like cognition and memory. Its particular role in explaining the importance of early life/social experiences on adult behavioral patterns has caught the attention of scientists and has spawned the exciting new field of behavioral epigenetics which may hold the key to explaining many complex behavioral paradigms. Epigenetic deregulation is known to be central in the etiology of several neuropsychiatric disorders which underscore the importance of understanding these mechanisms more thoroughly to elucidate novel and effective therapeutic approaches. In this review we present an overview of the findings which point to the essential role played by epigenetics in the vertebrate nervous system.     

Assessing Primary Neurogenesis in Xenopus Embryos Using Immunostaining

Primary neurogenesis is a dynamic and complex process during embryonic development that sets up the initial layout of the central nervous system. During this process, a portion of neural stem cells undergo differentiation and give rise to the first populations of differentiated primary neurons within the nascent central nervous system. Several vertebrate model organisms have been used to explore the mechanisms of neural cell fate specification, patterning, and differentiation. Among these is the African clawed frog, Xenopus, which provides a powerful system for investigating the molecular and cellular mechanisms responsible for primary neurogenesis due to its rapid and accessible development and ease of embryological and molecular manipulations. Here, we present a convenient and rapid method to observe the different populations of neuronal cells within Xenopus central nervous system. Using antibody staining and immunofluorescence on sections of Xenopus embryos, we are able to observe the locations of neural stem cells and differentiated primary neurons during primary neurogenesis.     

长链非编码RNA在神经系统中的研究进展

长链非编码RNA (long noncoding RNA, lncRNA)是多种复杂有机体转录组中最主要的一类转录本. lncRNA在各种生物之间序列保守性差、表达量普遍比较低.与编码基因相比,lncRNA有相似的启动子区域以及剪切位点,具有较好的细胞和组织特异性分布,尤其在神经系统中具有较为丰富的表达,提示它们在神经系统中具有不可忽视的作用.本文围绕近几年lncRNA在神经系统方面的最新研究成果,总结了lncRNA对中枢和外周神经系统发育以及对神经系统功能等方面的调控作用及机制.同时展望了有关lncRNA研究的新理念和新技术及对未来神经科学研究的推动作用.     

Culture of mouse neural stem cell precursors

Primary neural stem cell cultures are useful for studying the mechanisms underlying central nervous system development. Stem cell research will increase our understanding of the nervous system and may allow us to develop treatments for currently incurable brain diseases and injuries. In addition, stem cells should be used for stem cell research aimed at the detailed study of mechanisms of neural differentiation and transdifferentiation and the genetic and environmental signals that direct the specialization of the cells into particular cell types. This video demonstrates a technique used to disaggregate cells from the embryonic day 12.5 mouse dorsal forebrain. The dissection procedure includes harvesting E12.5 mouse embryos from the uterus, removing the "skin" with fine dissecting forceps and finally isolating pieces of cerebral cortex. Following the dissection, the tissue is digested and mechanically dissociated. The resuspended dissociated cells are then cultured in "stem cell" media that favors growth of neural stem cells.     

细胞黏附和突触发生

突触是神经网络中神经细胞间相互连接的基本工作单位。突触的分子构建是一个引人入胜的问题,数十年来一直吸引着科学家们的注意。冯德培和许多其他科学家早期在神经肌肉接头领域做出了开创性的研究工作。至今,神经肌肉接头仍是一个杰出的突触标本,为我们研究中枢神经系统的突触形成铺平了道路。近期的研究又有新的亮点,发现一组细胞黏附分子具有很强的突触发生作用,使中枢突触形成的分子机制更加明朗。本文综述了这些表达在非神经细胞里能引起中枢突触形成的细胞黏附分子的功能与特性。     

Cell fate control in the developing central nervous system

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases.     

Roles of the ubiquitin-proteosome system in neurogenesis

The ubiquitin-proteosome system (UPS) is a non-lysosomal proteolysis system involved in the degradation of irrelevant/misfolded intracellular proteins. The protein substrates of this system are tagged by ubiquitin in sequential reactions that target them for proteasome-dependent destruction. In the developing central nervous system, ubiquitin-mediated proteolysis has recently emerged as an important player in the regulation of neural progenitor proliferation, cell specification, neuronal differentiation, maturation, and migration. E3 ubiquitin ligases are crucial components in the UPS because they provide the specificity that determines which substrates are targeted for ubiquitin-dependent proteolysis. In this review, we discuss the molecular mechanisms of the UPS, focusing primarily on the roles of E3 ligases and their substrates in sequential steps of neurogenesis.     

New perspectives of tissue remodelling with neural stem and progenitor cell-based therapies

Compelling evidence exists that neural stem cell-based therapies protect the central nervous system (CNS) from chronic inflammatory degeneration, such as that occurring in experimental autoimmune encephalomyelitis and stroke. It was first assumed that stem cells directly replace lost cells but it is now becoming clearer that they might be able to protect the nervous system through mechanisms other than cell replacement. In immune-mediated experimental demyelination and stroke, transplanted neural stem/precursor cells (NPCs) are able to mediate efficient bystander myelin repair and axonal rescue. This is dependent on multiple capacities that transplanted NPCs exhibit within specific microenvironments after transplantation. However, a comprehensive understanding of the mechanisms by which NPCs exert their therapeutic impact is lacking. Here we will review some of the most recent evidence--and discuss some of the likely mechanisms--that support the remarkable capacity of NPCs to cross-talk with endogenous cells and to remodel the injured nervous system when applied as novel therapeutic regimes. We foresee that the exploitation of the innate mechanisms regulating these modalities of cell-to-cell communication has realistic chances of revolutionizing most of the actual understanding of stem cell biology and its application to regenerative medicine and CNS repair.     

FGF binding proteins (FGFBPs): Modulators of FGF signaling in the developing,adult, and stressed nervous system

Members of the fibroblast growth factor (FGF) family are involved in a variety of cellular processes. In the nervous system, they affect the differentiation and migration of neurons, the formation and maturation of synapses, and the repair of neuronal circuits following insults. Because of the varied yet critical functions of FGF ligands, their availability and activity must be tightly regulated for the nervous system, as well as other tissues, to properly develop and function in adulthood. In this regard, FGF binding proteins (FGFBPs) have emerged as strong candidates for modulating the actions of secreted FGFs in neural and non-neural tissues. Here, we will review the roles of FGFBPs in the peripheral and central nervous systems.     

脐带血来源干细胞神经分化的研究进展

中枢神经系统损伤后的自身修复能力有限,因而研究者致力于寻找一种合适的细胞进行移植以代替受损的神经细胞修复神经损伤。近年来的研究表明,脐带血干细胞能够在体外诱导条件下向神经样细胞分化,并在动物体内实验中促进神经损伤的恢复,有可能作为一种有效的细胞资源,应用于人类中枢神经系统疾病的细胞替代治疗以及神经保护与支持。     

IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes

Adult multipotent neural progenitor cells can differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. However, it is unclear whether IGF-I affects multipotent neural progenitor cells. Here, we show that IGF-I stimulates the differentiation of multipotent adult rat hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein signaling. Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers. These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.     

Role of nitric oxide in central sympathetic outflow

The gaseous molecule nitric oxide (NO) plays an important role in cardiovascular homeostasis. It plays this role by its action on both the central and peripheral autonomic nervous systems. In this review, the central role of NO in the regulation of sympathetic outflow and subsequent cardiovascular control is examined. After a brief introduction concerning the location of NO synthase (NOS) containing neurons in the central nervous system (CNS), studies that demonstrate the central effect of NO by systemic administration of NO modulators will be presented. The central effects of NO as assessed by intracerebroventricular, intracisternal, or direct injection within the specific central areas is also discussed. Our studies demonstrating specific medullary and hypothalamic sites involved in sympathetic outflow are summarized. The review will be concluded with a discussion of the role of central NO mechanisms in the altered sympathetic outflow in disease states such as hypertension and heart failure.     

Epigenetic mechanisms regulating fate specification of neural stem cells

Neural stem cells (NSCs) possess the ability to self-renew and to differentiate along neuronal and glial lineages. These processes are defined by the dynamic interplay between extracellular cues including cytokine signalling and intracellular programmes such as epigenetic modification. There is increasing evidence that epigenetic mechanisms involving, for example, changes in DNA methylation, histone modification and non-coding RNA expression are closely associated with fate specification of NSCs. These epigenetic alterations could provide coordinated systems for regulating gene expression at each step of neural cell differentiation. Here we review the roles of epigenetics in neural fate specification in the mammalian central nervous system.