scholarly journals Cannabinoid Type 1 Receptor is Undetectable in Rodent and Primate Cerebral Neural Stem Cells but Participates in Radial Neuronal Migration

2020 ◽  
Vol 21 (22) ◽  
pp. 8657
Author(s):  
Yury M. Morozov ◽  
Ken Mackie ◽  
Pasko Rakic
Keyword(s):  
Stem Cells ◽  
Cerebral Cortex ◽  
Neural Stem Cells ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Cortical Plate ◽  
Projection Neurons ◽  
Embryonic Mouse ◽  
Cannabinoid Type 1 Receptor

Cannabinoid type 1 receptor (CB1R) is expressed and participates in several aspects of cerebral cortex embryonic development as demonstrated with whole-transcriptome mRNA sequencing and other contemporary methods. However, the cellular location of CB1R, which helps to specify molecular mechanisms, remains to be documented. Using three-dimensional (3D) electron microscopic reconstruction, we examined CB1R immunolabeling in proliferating neural stem cells (NSCs) and migrating neurons in the embryonic mouse (Mus musculus) and rhesus macaque (Macaca mulatta) cerebral cortex. We found that the mitotic and postmitotic ventricular and subventricular zone (VZ and SVZ) cells are immunonegative in both species while radially migrating neurons in the intermediate zone (IZ) and cortical plate (CP) contain CB1R-positive intracellular vesicles. CB1R immunolabeling was more numerous and more extensive in monkeys compared to mice. In CB1R-knock out mice, projection neurons in the IZ show migration abnormalities such as an increased number of lateral processes. Thus, in radially migrating neurons CB1R provides a molecular substrate for the regulation of cell movement. Undetectable level of CB1R in VZ/SVZ cells indicates that previously suggested direct CB1R-transmitted regulation of cellular proliferation and fate determination demands rigorous re-examination. More abundant CB1R expression in monkey compared to mouse suggests that therapeutic or recreational cannabis use may be more distressing for immature primate neurons than inferred from experiments with rodents.

scholarly journals Oligomeric and Fibrillar Species of Aβ42 Diversely Affect Human Neural Stem Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9537
Author(s):  
Adela Bernabeu-Zornoza ◽  
Raquel Coronel ◽  
Charlotte Palmer ◽  
Victoria López-Alonso ◽  
Isabel Liste
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Amyloid Β ◽  
Human Neural Stem Cells ◽  
High Concentrations ◽  
Aβ42 Peptide

Amyloid-β 42 peptide (Aβ1-42 (Aβ42)) is well-known for its involvement in the development of Alzheimer’s disease (AD). Aβ42 accumulates and aggregates in fibers that precipitate in the form of plaques in the brain causing toxicity; however, like other forms of Aβ peptide, the role of these peptides remains unclear. Here we analyze and compare the effects of oligomeric and fibrillary Aβ42 peptide on the biology (cell death, proliferative rate, and cell fate specification) of differentiating human neural stem cells (hNS1 cell line). By using the hNS1 cells we found that, at high concentrations, oligomeric and fibrillary Aβ42 peptides provoke apoptotic cellular death and damage of DNA in these cells, but Aβ42 fibrils have the strongest effect. The data also show that both oligomeric and fibrillar Aβ42 peptides decrease cellular proliferation but Aβ42 oligomers have the greatest effect. Finally, both, oligomers and fibrils favor gliogenesis and neurogenesis in hNS1 cells, although, in this case, the effect is more prominent in oligomers. All together the findings of this study may contribute to a better understanding of the molecular mechanisms involved in the pathology of AD and to the development of human neural stem cell-based therapies for AD treatment.

scholarly journals Ghrelin regulates cell cycle-related gene expression in cultured hippocampal neural stem cells

2016 ◽  
Vol 230 (2) ◽  
pp. 239-250 ◽  
Author(s):  
Hyunju Chung ◽  
Seungjoon Park
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Janus Kinase ◽  
Nuclear Antigen ◽  
Protein Levels ◽  
Proliferative Effect ◽  
Hippocampal Neural Stem Cells

We have previously demonstrated that ghrelin stimulates the cellular proliferation of cultured adult rat hippocampal neural stem cells (NSCs). However, little is known about the molecular mechanisms by which ghrelin regulates cell cycle progression. The purpose of this study was to investigate the potential effects of ghrelin on cell cycle regulatory molecules in cultured hippocampal NSCs. Ghrelin treatment increased proliferation assessed by CCK-8 proliferation assay. The expression levels of proliferating cell nuclear antigen and cell division control 2, well-known cell-proliferating markers, were also increased by ghrelin. Fluorescence-activated cell sorting analysis revealed that ghrelin promoted progression of cell cycle from G0/G1 to S phase, whereas this progression was attenuated by the pretreatment with specific inhibitors of MEK/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/Akt, mammalian target of rapamycin, and janus kinase 2/signal transducer and activator of transcription 3. Ghrelin-induced proliferative effect was associated with increased expression of E2F1 transcription factor in the nucleus, as determined by Western blotting and immunofluorescence. We also found that ghrelin caused an increase in protein levels of positive regulators of cell cycle, such as cyclin A and cyclin-dependent kinase (CDK) 2. Moreover, p27KIP1 and p57KIP2 protein levels were reduced when cell were exposed to ghrelin, suggesting downregulation of CDK inhibitors may contribute to proliferative effect of ghrelin. Our data suggest that ghrelin targets both cell cycle positive and negative regulators to stimulate proliferation of cultured hippocampal NSCs.

scholarly journals Adult Neural Stem Cells: Basic Research and Production Strategies for Neurorestorative Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
E. M. Samoilova ◽  
V. A. Kalsin ◽  
N. M. Kushnir ◽  
D. A. Chistyakov ◽  
A. V. Troitskiy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Nervous Tissue ◽  
Molecular Mechanisms ◽  
Somatic Cells ◽  
Basic Research ◽  
Neural Cells ◽  
Pluripotent State ◽  
Increased Risk ◽  
Object Of Study

Over many decades, constructing genetically and phenotypically stable lines of neural stem cells (NSC) for clinical purposes with the aim of restoring irreversibly lost functions of nervous tissue has been one of the major goals for multiple research groups. The unique ability of stem cells to maintain their own pluripotent state even in the adult body has made them into the choice object of study. With the development of the technology for induced pluripotent stem cells (iPSCs) and direct transdifferentiation of somatic cells into the desired cell type, the initial research approaches based on the use of allogeneic NSCs from embryonic or fetal nervous tissue are gradually becoming a thing of the past. This review deals with basic molecular mechanisms for maintaining the pluripotent state of embryonic/induced stem and reprogrammed somatic cells, as well as with currently existing reprogramming strategies. The focus is on performing direct reprogramming while bypassing the stage of iPSCs which is known for genetic instability and an increased risk of tumorigenesis. A detailed description of various protocols for obtaining reprogrammed neural cells used in the therapy of the nervous system pathology is also provided.

scholarly journals Loss of postnatal quiescence of neural stem cells through mTOR activation upon genetic removal of cysteine string protein-α

2019 ◽  
Vol 116 (16) ◽  
pp. 8000-8009 ◽  
Author(s):  
Jose L. Nieto-González ◽  
Leonardo Gómez-Sánchez ◽  
Fabiola Mavillard ◽  
Pedro Linares-Clemente ◽  
María C. Rivero ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Molecular Mechanisms ◽  
Radial Glia ◽  
Brain Dysfunction ◽  
Mtor Signaling ◽  
Cysteine String Protein ◽  
Newborn Neurons

Neural stem cells continuously generate newborn neurons that integrate into and modify neural circuitry in the adult hippocampus. The molecular mechanisms that regulate or perturb neural stem cell proliferation and differentiation, however, remain poorly understood. Here, we have found that mouse hippocampal radial glia-like (RGL) neural stem cells express the synaptic cochaperone cysteine string protein-α (CSP-α). Remarkably, in CSP-α knockout mice, RGL stem cells lose quiescence postnatally and enter into a high-proliferation regime that increases the production of neural intermediate progenitor cells, thereby exhausting the hippocampal neural stem cell pool. In cell culture, stem cells in hippocampal neurospheres display alterations in proliferation for which hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway is the primary cause of neurogenesis deregulation in the absence of CSP-α. In addition, RGL cells lose quiescence upon specific conditional targeting of CSP-α in adult neural stem cells. Our findings demonstrate an unanticipated cell-autonomic and circuit-independent disruption of postnatal neurogenesis in the absence of CSP-α and highlight a direct or indirect CSP-α/mTOR signaling interaction that may underlie molecular mechanisms of brain dysfunction and neurodegeneration.

scholarly journals Insights into the Biology and Therapeutic Applications of Neural Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Lachlan Harris ◽  
Oressia Zalucki ◽  
Michael Piper ◽  
Julian Ik-Tsen Heng
Keyword(s):  
Stem Cells ◽  
Cerebral Cortex ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Human Brain ◽  
Therapeutic Potential ◽  
Biological Significance ◽  
Adult Brain ◽  
Cognitive Capacity ◽  
Molecular Characteristics

The cerebral cortex is essential for our higher cognitive functions and emotional reasoning. Arguably, this brain structure is the distinguishing feature of our species, and yet our remarkable cognitive capacity has seemingly come at a cost to the regenerative capacity of the human brain. Indeed, the capacity for regeneration and neurogenesis of the brains of vertebrates has declined over the course of evolution, from fish to rodents to primates. Nevertheless, recent evidence supporting the existence of neural stem cells (NSCs) in the adult human brain raises new questions about the biological significance of adult neurogenesis in relation to ageing and the possibility that such endogenous sources of NSCs might provide therapeutic options for the treatment of brain injury and disease. Here, we highlight recent insights and perspectives on NSCs within both the developing and adult cerebral cortex. Our review of NSCs during development focuses upon the diversity and therapeutic potential of these cells for use in cellular transplantation and in the modeling of neurodevelopmental disorders. Finally, we describe the cellular and molecular characteristics of NSCs within the adult brain and strategies to harness the therapeutic potential of these cell populations in the treatment of brain injury and disease.

Brain tumor stem cells

2010 ◽  
Vol 391 (6) ◽  
Author(s):  
Thomas Palm ◽  
Jens C. Schwamborn
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Neural Stem Cells ◽  
Molecular Mechanisms ◽  
Adult Brain ◽  
Tumor Stem Cells ◽  
Cellular Mechanisms ◽  
Cell Pool ◽  
Brain Tumor Stem Cells ◽  
Stem Cell Pool

Abstract Since the end of the ‘no-new-neuron’ theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies.

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