scholarly journals Early life stress decreases the proliferation and numbers of adult hypothalamic neural stem cells

2019 ◽  
Author(s):  
Pascal Bielefeld ◽  
Maralinde R. Abbink ◽  
Anna R. Davidson ◽  
Paul J. Lucassen ◽  
Aniko Korosi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Life Stress ◽  
Early Life ◽  
Cell Function ◽  
Early Life Stress ◽  
Adult Brain ◽  
Wide Range

AbstractEarly life stress (ELS) is a potent environmental factor that can confer enduring effects on brain structure and function. Exposure to stress during early life has been linked to a wide range of physiopathological consequences later in life. In particular, ELS has been shown to have lasting effects on neurogenesis in the adult brain, suggesting that ELS is a significant regulator of adult neural stem cell function. Here, we investigated the effect of ELS on the numbers and proliferation of neural stem cells in the hypothalamus of adult mice. We show that ELS has long term negative effects on hypothalamic neural stem cell numbers and on their proliferation. Specifically, ELS reduced the total numbers of PCNA+ cells present in hypothalamic areas surrounding the 3rd ventricle; the numbers of PCNA+/Sox2+/Nestin-GFP+ cells present in the medial eminence at the base of the 3rd ventricle; and the number of β-tanycytes around the ventral 3rd ventricle, without affecting the numbers of α-tanycytes in more dorsal areas. These results suggest that a reduction of proliferation and tanycyte numbers contributes to the effects of ELS on the hypothalamus and its consequent physiological alterations.

scholarly journals Adult Neurogenesis and the Promise of Adult Neural Stem Cells

2019 ◽  
Vol 13 ◽  
pp. 117906951985687 ◽  
Author(s):  
Hiyaa S Ghosh
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Adult Neurogenesis ◽  
Therapeutic Potential ◽  
Precursor Cells ◽  
Adult Brain ◽  
Adult Neural Stem Cell ◽  
Dividing Cells

The adult brain, even though largely postmitotic, is now known to have dividing cells that can make both glia and neurons. Of these, the precursor cells that have the potential to make new neurons in the adult brain have attracted great attention from researchers, anticipating their therapeutic potential for neurodegenerative conditions. In this review, I will focus on adult neurogenesis, from the perspective of the overall neurogenic potential in the adult brain, current understanding of the ‘adult neural stem cell’, and the importance of niche as a decisive factor for neurogenesis under homeostasis and pathologic conditions.

scholarly journals Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture

2017 ◽  
Author(s):  
Maria Angeles Marques-Torrejon ◽  
Ester Gangoso ◽  
Steven M. Pollard
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Ex Vivo ◽  
Brain Slices ◽  
Genetically Engineered ◽  
Adult Brain ◽  
Host Interactions ◽  
The Brain

AbstractGlioblastoma (GBM) is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as GBM stem cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM tumours can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human). Unfortunately, these approaches are expensive, time-consuming, low-throughput and ill-suited for monitoring of live cell behaviours. Here we explored whole adult brain coronal organotypic slices as a complementary strategy to remove the experimental bottleneck. Mouse adult brain slices remain viable in a neural stem cell serum-free basal media for several weeks. GSCs can therefore be easily microinjected into specific anatomical sites ex vivo. We demonstrated distinct responses of engrafted GSCs to different microenvironments in the brain. Within the subependymal zone – one of the adult neural stem cell niches – a subset of injected tumour cells could effectively engraft and respond to endothelial niche signals. GSCs transplanted slices were treated with the anti-mitotic drug temozolomide as proof-of-principle of the utility in modelling responses to existing treatments. Thus, engraftment of mouse or human GSCs onto whole brain coronal organotypic brain slices provides a convenient experimental model for studies of GSC-host interactions and preclinical testing of candidate therapeutic agents.

scholarly journals Early life stress decreases cell proliferation and the number of putative adult neural stem cells in the adult hypothalamus

Stress ◽  
2021 ◽  
pp. 1-7
Author(s):  
Pascal Bielefeld ◽  
Maralinde R. Abbink ◽  
Anna R. Davidson ◽  
Niels Reijner ◽  
Oihane Abiega ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Neural Stem Cells ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Adult Neural Stem Cells

scholarly journals Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis

2018 ◽  
Author(s):  
Mary Youssef ◽  
Varsha S. Krish ◽  
Greer S. Kirshenbaum ◽  
Piray Atsak ◽  
Tamara J. Lass ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Early Life ◽  
Cell Function ◽  
Cell Lineage ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Stem Cell Lineage

AbstractEnvironmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis.

Abstract 17: Early Life Stress Sensitizes The Angiotensin II-elicited Hypertensive Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Baojian Xue ◽  
Terry Beltz ◽  
Fang Guo ◽  
David M Pollock ◽  
Jennifer S Pollock ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Proinflammatory Cytokines ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Male Rats ◽  
Sprague Dawley ◽  
Cns Inflammation ◽  
Wide Range ◽  
The Brain

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.

scholarly journals Early life stress delays hippocampal development and diminishes the adult stem cell pool in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mary Youssef ◽  
Piray Atsak ◽  
Jovani Cardenas ◽  
Stylianos Kosmidis ◽  
E. David Leonardo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Adult Stem Cell ◽  
Cell Pool ◽  
Hippocampal Development ◽  
Stem Cell Pool

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 Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2)

2020 ◽  
Vol 91 (4) ◽  
pp. 396-401 ◽  
Author(s):  
Keith W Muir ◽  
Diederik Bulters ◽  
Mark Willmot ◽  
Nikola Sprigg ◽  
Anand Dixit ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Multicentre Study ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Upper Limb ◽  
Limb Movement ◽  
Human Neural Stem Cells ◽  
Human Neural Stem Cell ◽  
Cell Implantation

BackgroundHuman neural stem cell implantation may offer improved recovery from stroke. We investigated the feasibility of intracerebral implantation of the allogeneic human neural stem cell line CTX0E03 in the subacute—chronic recovery phase of stroke and potential measures of therapeutic response in a multicentre study.MethodsWe undertook a prospective, multicentre, single-arm, open-label study in adults aged >40 years with significant upper limb motor deficits 2–13 months after ischaemic stroke. 20 million cells were implanted by stereotaxic injection to the putamen ipsilateral to the cerebral infarct. The primary outcome was improvement by 2 or more points on the Action Research Arm Test (ARAT) subtest 2 at 3 months after implantation.FindingsTwenty-three patients underwent cell implantation at eight UK hospitals a median of 7 months after stroke. One of 23 participants improved by the prespecified ARAT subtest level at 3 months, and three participants at 6 and 12 months. Improvement in ARAT was seen only in those with residual upper limb movement at baseline. Transient procedural adverse effects were seen, but no cell-related adverse events occurred up to 12 months of follow-up. Two deaths were unrelated to trial procedures.InterpretationAdministration of human neural stem cells by intracerebral implantation is feasible in a multicentre study. Improvements in upper limb function occurred at 3, 6 and 12 months, but not in those with absent upper limb movement at baseline, suggesting a possible target population for future controlled trials.FundingReNeuron, Innovate UK (application no 32074-222145).Trial registration numberEudraCT Number: 2012-003482-18

The adaptive and maladaptive continuum of stress responses – a hippocampal perspective

2015 ◽  
Vol 26 (4) ◽  
Author(s):  
Deepika Suri ◽  
Vidita A. Vaidya
Keyword(s):  
Stress Responses ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Negative Consequences ◽  
Functional Responses ◽  
Physiological Level ◽  
Early Stress ◽  
Wide Range ◽  
Potential Factors

AbstractExposure to stressors elicits a spectrum of responses that span from potentially adaptive to maladaptive consequences at the structural, cellular and physiological level. These responses are particularly pronounced in the hippocampus where they also appear to influence hippocampal-dependent cognitive function and emotionality. The factors that influence the nature of stress-evoked consequences include the chronicity, severity, predictability and controllability of the stressors. In addition to adult-onset stress, early life stress also elicits a wide range of structural and functional responses, which often exhibit life-long persistence. However, the outcome of early stress exposure is often contingent on the environment experienced in adulthood, and could either aid in stress coping or could serve to enhance susceptibility to the negative consequences of adult stress. This review comprehensively examines the consequences of adult and early life stressors on the hippocampus, with a focus on their effects on neurogenesis, neuronal survival, structural and synaptic plasticity and hippocampal-dependent behaviors. Further, we discuss potential factors that may tip stress-evoked consequences from being potentially adaptive to largely maladaptive.

Multifunctional silica-coated iron oxide nanoparticles: a facile four-in-one system for in situ study of neural stem cell harvesting

2014 ◽  
Vol 175 ◽  
pp. 13-26 ◽  
Author(s):  
Yung-Kang Peng ◽  
Cathy N. P. Lui ◽  
Tsen-Hsuan Lin ◽  
Chen Chang ◽  
Pi-Tai Chou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Iron Oxide ◽  
Magnetic Resonance ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Cell Therapies ◽  
Bimodal Imaging

Neural stem cells (NSCs), which generate the main phenotypes of the nervous system, are multipotent cells and are able to differentiate into multiple cell types via external stimuli from the environment. The extraction, modification and re-application of NSCs have thus attracted much attention and raised hopes for novel neural stem cell therapies and regenerative medicine. However, few studies have successfully identified the distribution of NSCs in a live brain and monitored the corresponding extraction processes both in vitro and in vivo. To address those difficulties, in this study multi-functional uniform nanoparticles comprising an iron oxide core and a functionalized silica shell (Fe3O4@SiO2(FITC)-CD133, FITC: a green emissive dye, CD133: anti-CD133 antibody) have been strategically designed and synthesized for use as probe nanocomposites that provide four-in-one functionality, i.e., magnetic agitation, dual imaging (both magnetic resonance and optical) and specific targeting. It is shown that these newly synthesized Fe3O4@SiO2(FITC)-CD133 particles have clearly demonstrated their versatility in various applications. (1) The magnetic core enables magnetic cell collection and T2 magnetic resonance imaging. (2) The fluorescent FITC embedded in the silica framework enables optical imaging. (3) CD133 anchored on the outermost surface is demonstrated to be capable of targeting neural stem cells for cell collection and bimodal imaging.

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