Adult neurogenesis has been questioned for many years. In the early 1900s, a dogma was established that denied new neuron formation in the adult brain. In the last century however, new discoveries have demonstrated the real existence of proliferation in the adult brain, and in the last decade, these studies led to the identification of neural stem cells in mammals. Adult neural stem cells are undifferentiated cells that are present in the adult brain and are capable of dividing and differentiating into glia and new neurons. Newly formed neurons terminally differentiate into mature neurons in the olfactory bulb and the dentate gyrus of the hippocampus. Since then, a number of new research lines have emerged whose common objective is the phenotypical and molecular characterization of brain stem cells. As a result, new therapies are successfully being applied to animal models for certain neurodegenerative diseases or stroke. At present, and in years to come, this finding extends to the adult human brain, and gives reason and hope to all the previous studies.
Adult neurogenesis has been questioned for many years. In the early 1900s, a dogma was established that denied new neuron formation in the adult brain. Adult neural stem cells are undifferentiated cells that are present in the adult brain and are capable of dividing and differentiating into glia and new neurons.
The prenatal human brain undergoes rapid development during the second trimester from a pool of neural stem cells (NSCs) known as radial glia (RG), which give rise to the neurons, oligodendrocytes, and astrocytes of the mature brain. We describe a method for the prospective isolation of multiple neural stem and progenitor cell (NSPC) populations from the developing human brain using various cell--surface markers that constitute their immunophenotype. The distinct NSPC populations include ventricular and outer radial glia (vRG, oRG), cells of excitatory and inhibitory neuronal lineages, oligodendrocyte precursor cells (OPCs), and astrocyte lineage cells. The purity of isolated NSPCs was assessed by correlating the expressed transcriptomes of individual index--sorted cells with their immunophenotype. We then confirmed the functional purity of isolated NSPCs regarding their lineage output potential through various in vitro differentiation assays, and through in vivo transplantation into the lateral ventricles of neonatal immunodeficient mouse brains. Histological analysis using human specific antibodies showed robust site--specific migration and engraftment of human NSPC subsets, which, after differentiation in vivo, gave rise to all three mature neural lineages in adult murine brains 6 months post--engraftment.
Over the last decade, neural stem cell research has provided penetrating insights into the plasticity and regenerative potential of the brain. Stem cells have been isolated from embryonic as well as adult central nervous system (CNS). Many non-CNS mammalian tissues also contain stem cells with a more limited repertoire: the replacement of tissue-specific cells throughout the li- time of the organism. Progress has been made in understanding fundamental stem cell properties that depend on the interplay of extrinsic signaling factors with intrinsic genetic programs within critical time frames. With this growing knowledge, scientists have been able to change a neural stem cell’s fate. - der certain conditions, neural stem cells have been induced to differentiate into cells outside the expected neural lineage and conversely, stem cells from nonneural tissue have been shown to transdifferentiate into cells with distinct neural phenotypes. At the moment, there is an accelerated effort to identify a readily ava- able, socially acceptable stem cell that can be induced to proliferate in an und- ferentiated state and that can be manipulated at will to generate diverse cells types. We are on the threshold of a great new therapeutic era of cellular therapy that has as great, if not greater, potential as the current pharmacologic era, g- rified by antibiotics, anesthetics, pain killers, immunosuppressants, and psyc- tropics.
The fact that the mammalian central nervous system is mostly made up of perennial elements accounting for its well known uncapability to undergo physiological cell renewal and post-lesion repair has represented a dogma for most of the XXth century. Yet, research carried out starting from the sixties in a rather sceptic milieu, and exponentially expanded at the beginning of the nineties with the definitive demonstration that neurogenesis actually takes place in the adult brain and that it is sustained by neural stem cells, opened a new, challenging field in neuroscience. In the last fifteen years, such a field has been tackled by interdisciplinary approaches thus spreading into several ramifications, often referred either more generally to as developmental neurobiology and structural plasticity , or more specifically to as adult neurogenesis . The aims of these studies have become more focused in a wide range of topics, spanning from the detailed morphological/molecular analysis of neurogenic sites to the migration/specification/integration of newlyborn cell precursors into neuronal circuits; from the in vivo identification of cell types and their functional relationships within the neural stem cell niches to the in vitro isolation and characterization of neural stem cells in the perspective of brain repair. In the last few years, in spite of a huge amount of information gathered around the issue of neurogenesis, new elements of complexity have arisen, thus leaving open many questions. It is now clear that persistent neurogenesis do not faithfully reproduce embryonic developmental processes. Indeed, postnatal changes involving the structure/function of neurogenic sites and the neural stem cell niches contained herein, do occur in order to adapt to the mature nervous tissue. The recent finding that adult neural stem cells share a glial identity and directly derive from radial glia raises questions concerning the neuronal-glial relationships across pre- and post-natal development. The progeny of neuronal precursors must integrate into already established neural circuits, whose features change according to the pre- and post-natal developmental stages. In addition, the fact that neural stem cells isolated in vitro prevalently differentiate into astrocytes, whereas in vivo they produce mainly neurons, highlights the importance of epigenetic signals. Finally, substantial data recently obtained under a comparative profile reveal that persistent neurogenesis, although being a well preserved trait, shows remarkable differences among species and, possibly, interesting evolutionary adaptations. The comparative approach, both among mammals and among vertebrates, further reveals new elements of complexity linked to the different growth rates and lifespans. Yet, although introducing new questions about postnatal and adult stages in different species, this approach could provide insights as concerns the functional significance of persistent neurogenesis. Thus, 50 years after the first evidence that new neurons can be generated and added to a mature brain, the actual meaning of such a phenomenon in brain physiology as well as its usefulness in brain repair remain a matter of debate. We learned that neurogenesis can persist in restricted brain sites, whereby it undergoes complex cell/molecular regulation, whereas in the rest of the nervous system it remains as a potentiality. Hence, a better knowledge of the complex regulatory mechanisms underlying these processes should be attained to understand if and how endogenous neurogenesis can be exploited/modulated in the perspective of brain healing. This book, other than providing an overview of the state of the art in the field of postnatal and adult neurogenesis, tries to update our present knowledge about the postnatal changes of neurogenic processes and to place them in the context of a comparative vision. The attainment of this goal has been possible thanks to the contribution of many young scientists from different corners of the world, who have built their experience in neurogenesis during the last decade.
The enteric nervous system (ENS) is a complex neural network embedded in the gut wall that orchestrates the reflex behaviors of the intestine. The ENS is often referred to as the “little brain” in the gut because the ENS is more similar in size, complexity and autonomy to the central nervous system (CNS) than other components of the autonomic nervous system. Like the brain, the ENS is composed of neurons that are surrounded by glial cells. Enteric glia are a unique type of peripheral glia that are similar to astrocytes of the CNS. Yet enteric glial cells also differ from astrocytes in many important ways. The roles of enteric glial cell populations in the gut are beginning to come to light and recent evidence implicates enteric glia in almost every aspect of gastrointestinal physiology and pathophysiology. However, elucidating the exact mechanisms by which enteric glia influence gastrointestinal physiology and identifying how those roles are altered during gastrointestinal pathophysiology remain areas of intense research. The purpose of this e-book is to provide an introduction to enteric glial cells and to act as a resource for ongoing studies on this fascinating population of glia. Table of Contents: Introduction / A Historical Perspective on Enteric Glia / Enteric Glia: The Astroglia of the Gut / Molecular Composition of Enteric Glia / Development of Enteric Glia / Functional Roles of Enteric Glia / Enteric Glia and Disease Processes in the Gut / Concluding Remarks / References / Author Biography
Adult neural stem cells (NSCs) and neural progenitor cells (NPCs) have been the subject of significant research in recent times. Model organisms, including Drosophila melanogaster, have been used to gain insight into the origin and function of NSCs. To date, NSC-like cells, called neuroblasts, have been identified in Drosophila larvae. Whether NSCs or NPCs are also present in adults is unclear. The goal of my research is to identify and characterize NSCs/NPCs in theadult Drosophila brain and determine whether these cells are affected by aging. My findings indicate more cell division is present within the adult brain than previously thought. The majority of the dividing cells also do not appear to be glial or neuronal in nature suggesting the distinct possibility that these cells may be NSCs/NPCs. Insight into the function of NSCs/NPCs in Drosophila may lead to greater understanding of how injury, disease, and aging may effect NSC/NPC populations in mammals.
This updated edition collects cutting-edge techniques used to study neural stem and progenitor cells as well as the brain microenvironment. Featuring a wide range of technological advances in the study of neural stem cells, the volume highlights the promises of stem cell-based therapeutic applications for central nervous system ailments. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Neural Progenitor Cells: Methods and Protocols, Second Edition serves as an invaluable resource for the next generation of neuroscientists as they develop innovative experimental paradigms and progress toward therapeutic applications in the field of neurobiology.
In this volume outstanding specialists review the state of the art in nervous system research for all main invertebrate groups. They provide a comprehensive up-to-date analysis important for everyone working on neuronal aspects of single groups, as well as taking into account the phylogenesis of invertebrates. The articles report on recently gained knowledge about diversification in the invertebrate nervous systems, and demonstrate the analytical power of a comparative approach. Novel techniques in molecular and developmental biology are creating new perspectives that point toward a theoretical foundation for a modern organismic biology. The comparative approach, as documented here, will engage the interest of anyone challenged by the problem of structural diversification in biology.
The mature brain contains an incredible number and diversity of cells that are produced and maintained by heterogeneous pools of neural stem cells. Two distinct types of neural stem cells (NSCs) in the developing and adult mouse brain include primitive (p)NSCs and definitive (d)NSCs. PNSCs form clonogenic neurospheres when grown in LIF, arise ~E5.5, and persist into the adult brain. In this and other work we show adult pNSCs are very rare and quiescent, express Oct4, and give rise to GFAP+ definitive (d)NSCs that form neurospheres in EGF and FGF2. While pNSCs can serve as a reserve pool for an ablated dNSC population in the adult brain, characterization of this activation process remains of interest, and herein I propose this occurs through transition between unique molecular states. To better understand the functions of NSCs embryonically, we performed clonal lineage tracing within neurospheres grown in either LIF or EGF/FGF2, to enrich for neural progenitor cells (NPCs) directly downstream pNSCs or dNSCs, respectively. These clonal progenitor lineage tracing data allowed us to construct a hierarchy of progenitor subtypes downstream of pNSCs and dNSCs that were validated using single cell transcriptomics. Combined, these data provide single cell resolution of NPCs downstream of rare pNSCs that would likely be missed from population level analyses in vivo.
