scholarly journals Insights into the mechanism of adult neurogenesis - interview with Arturo Alvarez-Buylla

2020 ◽  
Vol 52 ◽  
Author(s):  
Diana Escalante-Alcalde ◽  
Jesús Chimal-Monroy
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Olfactory Bulb ◽  
Progenitor Cells ◽  
Adult Neurogenesis ◽  
Neural Development ◽  
Adult Brain ◽  
Laboratory Findings ◽  
Brain Circuits ◽  
The 1960S

Neurogenesis is the process by which new neurons are formed from progenitor cells. The adult nervous system was long considered unable to generate new neurons, especially in mammals. It was not until the 1960s that Joseph Altman and Gopal Das, using thymidine-H3 autoradiography to trace newly formed cells, that the first suggestions of new neurons added to the olfactory bulb and the dentate gyrus of the rat hippocampus came about. These observations remained controversial for many years as they went against the dogmatic view that the structure of the adult brain precluded processes of neurogenesis. It was not until two decades later that work in songbirds and then in mammals, not only confirmed that new neurons could be produced in the adult brain, but revealed basic processes of how young neurons are produced, how they could migrate long distances and become incorporated into adult brain circuits. Arturo Álvarez-Buylla has made important contributions to the understanding of the mechanism of adult neurogenesis, including the identification of the adult neural stem cells. Here we summarize a discussion with him related to the field of adult neurogenesis, the root of his interest in neural development and the ramifications of some of his laboratory findings.

scholarly journals Neural stem cells: involvement in adult neurogenesis and CNS repair

2008 ◽  
Vol 363 (1500) ◽  
pp. 2111-2122 ◽  
Author(s):  
Hideyuki Okano ◽  
Kazunobu Sawamoto
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Transplantation ◽  
Adult Neurogenesis ◽  
Embryonic Stem ◽  
Adult Brain ◽  
Therapeutic Interventions ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Recent advances in stem cell research, including the selective expansion of neural stem cells (NSCs) in vitro , the induction of particular neural cells from embryonic stem cells in vitro , the identification of NSCs or NSC-like cells in the adult brain and the detection of neurogenesis in the adult brain (adult neurogenesis), have laid the groundwork for the development of novel therapies aimed at inducing regeneration in the damaged central nervous system (CNS). There are two major strategies for inducing regeneration in the damaged CNS: (i) activation of the endogenous regenerative capacity and (ii) cell transplantation therapy. In this review, we summarize the recent findings from our group and others on NSCs, with respect to their role in insult-induced neurogenesis (activation of adult NSCs, proliferation of transit-amplifying cells, migration of neuroblasts and survival and maturation of the newborn neurons), and implications for therapeutic interventions, together with tactics for using cell transplantation therapy to treat the damaged CNS.

scholarly journals Localization of phosphotyrosine adaptor protein ShcD/SHC4 in the adult rat central nervous system

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hannah N. Robeson ◽  
Hayley R. Lau ◽  
Laura A. New ◽  
Jasmin Lalonde ◽  
John N. Armstrong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Olfactory Bulb ◽  
Adaptor Protein ◽  
Cell Types ◽  
Olfactory Nerve ◽  
Adult Brain ◽  
Specific Cell ◽  
Adult Rat ◽  
Fiber Tracts

Abstract Background Mammalian Shc (Src homology and collagen) proteins comprise a family of four phosphotyrosine adaptor molecules which exhibit varied spatiotemporal expression and signaling functions. ShcD is the most recently discovered homologue and it is highly expressed in the developing central nervous system (CNS) and adult brain. Presently however, its localization within specific cell types of mature neural structures has yet to be characterized. Results In the current study, we examine the expression profile of ShcD in the adult rat CNS using immunohistochemistry, and compare with those of the neuronally enriched ShcB and ShcC proteins. ShcD shows relatively widespread distribution in the adult brain and spinal cord, with prominent levels of staining throughout the olfactory bulb, as well as in sub-structures of the cerebellum and hippocampus, including the subgranular zone. Co-localization studies confirm the expression of ShcD in mature neurons and progenitor cells. ShcD immunoreactivity is primarily localized to axons and somata, consistent with the function of ShcD as a cytoplasmic adaptor. Regional differences in expression are observed among neural Shc proteins, with ShcC predominating in the hippocampus, cerebellum, and some fiber tracts. Interestingly, ShcD is uniquely expressed in the olfactory nerve layer and in glomeruli of the main olfactory bulb. Conclusions Together our findings suggest that ShcD may provide a distinct signaling contribution within the olfactory system, and that overlapping expression of ShcD with other Shc proteins may allow compensatory functions in the brain.

Development and regeneration in the central nervous system

1990 ◽  
Vol 327 (1239) ◽  
pp. 127-143 ◽  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Types ◽  
The Central Nervous System

As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.

scholarly journals Adult Neurogenesis in Peripheral Nervous System

2020 ◽  
Author(s):  
Yisheng Liu ◽  
Xiaosong Gu
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Sciatic Nerve ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Adult Neurogenesis ◽  
Lineage Tracing ◽  
Neuronal Stem Cells ◽  
Adult Rat ◽  
Nerve Staining

AbstractAlthough postnatal neurogenesis has been discovered in some regions of the peripheral nervous system (PNS), only indirect evidences indicated that some progenitors in the adult sciatic nerve and dorsal root ganglion (DRG) serve as a source of newly born sensory neurons. Here, we report the discovery of neurons and neuronal stem cells in the adult rat sciatic nerve. Lineage tracing detected a population of sciatic nerve neurons as progeny of adult neuronal stem cells. With the further finding of labeled DRG neurons in adult transgenic rats with local sciatic nerve staining, we propose a model of adult neurogenesis in the sciatic nerve in which neuronal stem cells in sciatic nerve mature as sensory neurons in adults along the sciatic nerve to DRG. This hypothesis provides a new way to understand sensory formation in adults. Those neuronal stem cells in the sciatic nerve may help to therapy of nerve trauma and disease in the future.

scholarly journals δ-protocadherins control neural progenitor cell proliferation by antagonizing Ryk and Wnt/β-catenin signaling

2020 ◽  
Author(s):  
Sayantanee Biswas ◽  
Michelle R. Emond ◽  
Kurtis Chenoweth ◽  
James D. Jontes
Keyword(s):  
Cell Proliferation ◽  
Nervous System ◽  
Progenitor Cells ◽  
Neural Development ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Progenitor Cell Proliferation ◽  
Canonical Wnt

AbstractThe proliferation of neural progenitor cells provides the cellular substrate from which the nervous system is sculpted during development. The δ-protocadherin family of homophilic cell adhesion molecules is essential for the normal development of the nervous system and has been linked to an array of neurodevelopmental disorders. However, the biological functions of δ-protocadherins are not well-defined. Here, we show that the δ-protocadherins regulate proliferation in neural progenitor cells, as lesions in each of six, individual δ-protocadherin genes increase cell division in the developing hindbrain. Moreover, Wnt/β-catenin signaling is upregulated in δ-protocadherin mutants and inhibition of the canonical Wnt pathway occludes the observed proliferation increases. We show that the δ-protocadherins physically associate with the Wnt receptor Ryk, and that Ryk is required for the increased proliferation in protocadherin mutants. Thus, the δ-protocadherins act as novel regulators of Wnt/β-catenin signaling during neural development and could provide lineage-restricted local regulation of canonical Wnt signaling and cell proliferation.

Adult Neurogenesis: Lessons from Crayfish and the Elephant in the Room

2016 ◽  
Vol 87 (3) ◽  
pp. 146-155 ◽  
Author(s):  
Barbara S. Beltz ◽  
Georg Brenneis ◽  
Jeanne L. Benton
Keyword(s):  
Stem Cells ◽  
Immune System ◽  
Neural Stem Cells ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Neural Precursor ◽  
Neural Precursors ◽  
Neurogenic Niche ◽  
Fetal Microchimerism ◽  
The Brain

The 1st-generation neural precursors in the crustacean brain are functionally analogous to neural stem cells in mammals. Their slow cycling, migration of their progeny, and differentiation of their descendants into neurons over several weeks are features of the neural precursor lineage in crayfish that also characterize adult neurogenesis in mammals. However, the 1st-generation precursors in crayfish do not self-renew, contrasting with conventional wisdom that proposes the long-term self-renewal of adult neural stem cells. Nevertheless, the crayfish neurogenic niche, which contains a total of 200-300 cells, is never exhausted and neurons continue to be produced in the brain throughout the animal's life. The pool of neural precursors in the niche therefore cannot be a closed system, and must be replenished from an extrinsic source. Our in vitro and in vivo data show that cells originating in the innate immune system (but not other cell types) are attracted to and incorporated into the neurogenic niche, and that they express a niche-specific marker, glutamine synthetase. Further, labeled hemocytes that undergo adoptive transfer to recipient crayfish generate cells in neuronal clusters in the olfactory pathway of the adult brain. These hemocyte descendants express appropriate neurotransmitters and project to target areas typical of neurons in these regions. These studies indicate that under natural conditions, the immune system provides neural precursors supporting adult neurogenesis in the crayfish brain, challenging the canonical view that ectodermal tissues generating the embryonic nervous system are the sole source of neurons in the adult brain. However, these are not the first studies that directly implicate the immune system as a source of neural precursor cells. Several types of data in mammals, including adoptive transfers of bone marrow or stem cells as well as the presence of fetal microchimerism, suggest that there must be a population of cells that are able to access the brain and generate new neurons in these species.

scholarly journals Genetic models to study adult neurogenesis.

2005 ◽  
Vol 52 (2) ◽  
pp. 359-372 ◽  
Author(s):  
Robert K Filipkowski ◽  
Anna Kiryk ◽  
Anna Kowalczyk ◽  
Leszek Kaczmarek
Keyword(s):  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factors ◽  
Growth Factors ◽  
Olfactory Bulb ◽  
Adult Neurogenesis ◽  
Knock Out ◽  
Associated Proteins ◽  
The Central Nervous System

In the central nervous system (CNS) generation of new neurons continues throughout adulthood, when it is limited to the olfactory bulb and hippocampus. The knowledge regarding the function of newly-generated neurons remains limited and is vigorously investigated using diverse approaches. Among these are genetically modified mice, most of them of knock-out type (KO). Results from 23 diverse KO mouse models demonstrate the importance of particular proteins (growth factors, nitric oxide synthases, receptors, cyclins/cyclin-associated proteins, transcription factors, etc.) in adult neurogenesis (ANGE) as well as separate it from developmental neurogenesis. These results bring us closer to revealing the function of newly generated neurons in adult brains.

DNA Methylation Abnormality and Brain Dysfunction of Neural Stem Cells Caused by Chronic Inflammation by Nanoparticle Exposure

Impact ◽  
2020 ◽  
Vol 2020 (7) ◽  
pp. 28-30
Author(s):  
Ken Tachibana
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neural Development ◽  
Broad Class ◽  
Cell Types ◽  
Associate Professor ◽  
Adult Brain ◽  
Wide Range ◽  
The Creation ◽  
The Brain

The biological development of a human is an extremely complex and delicate process. It starts from fertilisation and continues until long after birth. The creation and development of the brain is particularly complicated and susceptible to disruptions to its progression. The primary cells responsible for the development of the brain are the neural stem cells. These are a broad class of cells that can differentiate into the wide range of cell types that form the adult brain. To achieve this complex process, different cells need to undergo a range of gene expression changes at the right time. This is delicate and its disturbance is a key cause of pathology in a wide range of diseases. There are many external factors that are known to disrupt neural development however, there are several common chemicals whose effects remain largely unknown. One such group are broadly described as nanoparticles. These are small particles that are being increasingly used by many industries as they can help in the creation of products with better properties. However, their effect on the environment and the human body – particularly that of a developing brain – have been largely unexamined. Associate Professor Ken Tachibana of the Division of Hygienic Chemistry, Sanyo-Onoda City University, Japan is researching the effects of nanoparticles on neural development.

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