Substrates Influencing the Survival and Development of Neural Cells in Vitro

1988 ◽  
pp. 341-347
Author(s):  
D. Edgar ◽  
V. Nurcombe ◽  
U. Dohrmann
Keyword(s):  
Neural Cells ◽  
Survival And Development

scholarly journals Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 91
Author(s):  
Verena Schultz ◽  
Stephanie L. Cumberworth ◽  
Quan Gu ◽  
Natasha Johnson ◽  
Claire L. Donald ◽  
...  
Keyword(s):  
Nervous System ◽  
Neural Development ◽  
Zika Virus ◽  
Developmental Stages ◽  
Cell Types ◽  
Neural Cells ◽  
Zikv Infection ◽  
Axonal Pathology ◽  
Time Frames

Understanding how Zika virus (Flaviviridae; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination—which is critical for saltatory conduction and neuronal function—has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.

scholarly journals Sirtuin-2 Protects Neural Cells from Oxidative Stress and Is Elevated in Neurodegeneration

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Preeti Singh ◽  
Peter S. Hanson ◽  
Christopher M. Morris
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Brain Tissue ◽  
Postmortem Brain ◽  
Neural Cells ◽  
Compensatory Mechanism ◽  
Postmortem Brain Tissue ◽  
Lysine Deacetylases ◽  
Neuronal Stress

Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson’s disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along withα-synuclein aggregation. SIRT2 in human tissues was evaluated using Western blotting, immunohistochemistry, and fluorometric activity assays. In SH-SY5Y cells, elevated SIRT2 protected cells from rotenone or diquat induced cell death and enzymatic inhibition of SIRT2 enhanced cell death. SIRT2 protection was mediated, in part, through elevated SOD2 expression. SIRT2 reduced the formation ofα-synuclein aggregates but showed minimal colocalisation withα-synuclein. In postmortem PD brain tissue, SIRT2 activity was elevated compared to controls but also elevated in other neurodegenerative disorders. Results from both in vitro work and brain tissue suggest that SIRT2 is necessary for protection against oxidative stress and higher SIRT2 activity in PD brain may be a compensatory mechanism to combat neuronal stress.

Control of dorsoventral pattern in vertebrate neural development: induction and polarizing properties of the floor plate

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 105-122 ◽  
Author(s):  
Marysia Placzek ◽  
Toshiya Yamada ◽  
Marc Tessier-Lavigne ◽  
Thomas Jessell ◽  
Jane Dodd
Keyword(s):  
Neural Tube ◽  
Neural Development ◽  
Cell Types ◽  
Floor Plate ◽  
Neural Cells ◽  
Dorsoventral Patterning ◽  
Cellular Mechanisms ◽  
Cell Position

Distinct classes of neural cells differentiate at specific locations within the embryonic vertebrate nervous system. To define the cellular mechanisms that control the identity and pattern of neural cells we have used a combination of functional assays and antigenic markers to examine the differentiation of cells in the developing spinal cord and hindbrain in vivo and in vitro. Our results suggest that a critical step in the dorsoventral patterning of the embryonic CNS is the differentiation of a specialized group of midline neural cells, termed the floor plate, in response to local inductive signals from the underlying notochord. The floor plate and notochord appear to control the pattern of cell types that appear along the dorsoventral axis of the neural tube. The fate of neuroepithelial cells in the ventral neural tube may be defined by cell position with respect to the ventral midline and controlled by polarizing signals that originate from the floor plate and notochord.

scholarly journals Downregulation of the Central Noradrenergic System by Toxoplasma gondii Infection

2018 ◽  
Vol 87 (2) ◽  
Author(s):  
Isra Alsaady ◽  
Ellen Tedford ◽  
Mohammad Alsaad ◽  
Greg Bristow ◽  
Shivali Kohli ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Infection Intensity ◽  
Noradrenergic System ◽  
Neural Cells ◽  
Mrna Levels ◽  
Female Rat ◽  
Motor Impairments ◽  
Content Type ◽  
General Response

ABSTRACT Toxoplasma gondii is associated with physiological effects in the host. Dysregulation of catecholamines in the central nervous system has previously been observed in chronically infected animals. In the study described here, the noradrenergic system was found to be suppressed with decreased levels of norepinephrine (NE) in brains of infected animals and in infected human and rat neural cells in vitro. The mechanism responsible for the NE suppression was found to be downregulation of dopamine β-hydroxylase (DBH) gene expression, encoding the enzyme that synthesizes norepinephrine from dopamine, with downregulation observed in vitro and in infected brain tissue, particularly in the dorsal locus coeruleus/pons region. The downregulation was sex specific, with males expressing reduced DBH mRNA levels whereas females were unchanged. Rather, DBH expression correlated with estrogen receptor in the female rat brains for this estrogen-regulated gene. DBH silencing was not a general response of neurons to infection, as human cytomegalovirus did not downregulate DBH expression. The noradrenergic-linked behaviors of sociability and arousal were altered in chronically infected animals, with a high correlation between DBH expression and infection intensity. A decrease in DBH expression in noradrenergic neurons can elevate dopamine levels, which provides a possible explanation for mixed observations of changes in this neurotransmitter with infection. Decreased NE is consistent with the loss of coordination and motor impairments associated with toxoplasmosis. Further, the altered norepinephrine synthesis observed here may, in part, explain behavioral effects of infection and associations with mental illness.

scholarly journals A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress

2017 ◽  
Author(s):  
Nicola J. Drummond ◽  
Nick O. Davies ◽  
Janet E. Lovett ◽  
Mark R. Miller ◽  
Graeme Cook ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Damage ◽  
Radical Scavenging ◽  
Head Group ◽  
Neural Cells ◽  
Zebrafish Model ◽  
Free System ◽  
Age Related

AbstractExcessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson’s disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and mitochondrial localisation of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.

Selective Release of Calpain Produced αII-Spectrin (α-Fodrin) Breakdown Products by Acute Neuronal Cell Death

2002 ◽  
Vol 383 (5) ◽  
pp. 785-791 ◽  
Author(s):  
Satavisha Dutta ◽  
Yuk Chun Chiu ◽  
Albert W. Probert ◽  
Kevin K.W. Wang
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuronal Injury ◽  
Nmda Receptor Antagonist ◽  
Breakdown Product ◽  
Calpain Inhibitor ◽  
Neural Cells

Abstract Activation of calpain results in the breakdown of α II spectrin (αfodrin), a neuronal cytoskeleton protein, which has previously been detected in various in vitro and in vivo neuronal injury models. In this study, a 150 kDa spectrin breakdown product (SBDP150) was found to be released into the cellconditioned media from SHSY5Y cells treated with the calcium channel opener maitotoxin (MTX). SBDP150 release can be readily quantified on immunoblot using an SBDP150- specific polyclonal antibody. Increase of SBDP150 also correlated with cell death in a timedependent manner. MDL28170, a selective calpain inhibitor, was the only protease inhibitor tested that significantly reduced MTXinduced SBDP150 release. The cellconditioned media of cerebellar granule neurons challenged with excitotoxins (NMDA and kainate) also exhibited a significant increase of SBDP150 that was attenuated by pretreatment with an NMDA receptor antagonist, R()-3-(2-carbopiperazine-4-yl)propyl-1- phosphonic acid (CPP), and MDL28170. In addition, hypoxic/hypoglycemic challenge of cerebrocortical cultures also resulted in SBDP150 liberation into the media. These results support the theory that an antibody based detection of SBDP150 in the cellconditioned media can be utilized to quantify injury to neural cells. Furthermore, SBDP150 may potentially be used as a surrogate biomarker for acute neuronal injury in clinical settings.

scholarly journals Connective-Tissue Growth Factor (CTGF/CCN2) Induces Astrogenesis and Fibronectin Expression of Embryonic Neural Cells In Vitro

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0133689 ◽  
Author(s):  
Fabio A. Mendes ◽  
Juliana M. Coelho Aguiar ◽  
Suzana A. Kahn ◽  
Alice H. Reis ◽  
Luiz Gustavo Dubois ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Neural Cells ◽  
Fibronectin Expression

An in Vitro Model of Neural Trauma: Device Characterization and Calcium Response to Mechanical Stretch

2001 ◽  
Vol 123 (3) ◽  
pp. 247-255 ◽  
Author(s):  
Donna M. Geddes ◽  
Robert S. Cargill
Keyword(s):  
Strain Rate ◽  
In Vitro Model ◽  
Mechanical Stretch ◽  
Neural Cells ◽  
Novel Device ◽  
Loop Feedback ◽  
Closed Loop Feedback ◽  
Cellular Tolerance ◽  
Vitro Model

An in vitro model for neural trauma was characterized and validated. The model is based on a novel device that is capable of applying high strain rate, homogeneous, and equibiaxial deformation to neural cells in culture. The deformation waveform is fully arbitrary and controlled via closed-loop feedback. Intracellular calcium [Ca2+]i alterations were recorded in real time throughout the imposed strain with an epifluorescent microscopy system. Peak change in [Ca2+]i, recovery of [Ca2+]i, and percent responding NG108-15 cells were shown to be dependent on strain rate (1−1 to 10−1) and magnitude (0.1 to 0.3 Green’s Strain). These measures were also shown to depend significantly on the interaction between strain rate and magnitude. This model for neural trauma is a robust system that can be used to investigate the cellular tolerance and response to traumatic brain injury.

scholarly journals Induced Pluripotent HD Monkey Stem Cells Derived Neural Cells for Drug Discovery

2016 ◽  
Vol 22 (6) ◽  
pp. 696-705 ◽  
Author(s):  
Tanut Kunkanjanawan ◽  
Richard Carter ◽  
Kwan-Sung Ahn ◽  
Jinjing Yang ◽  
Rangsun Parnpai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Discovery ◽  
Trinucleotide Repeat ◽  
Yeast Cells ◽  
Neural Cells ◽  
Primate Model ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Induced Pluripotent

Huntington’s disease (HD) is a neurodegenerative disease caused by an expansion of CAG trinucleotide repeat (polyglutamine [polyQ]) in the huntingtin ( HTT) gene, which leads to the formation of mutant HTT (mHTT) protein aggregates. In the nervous system, an accumulation of mHTT protein results in glutamate-mediated excitotoxicity, proteosome instability, and apoptosis. Although HD pathogenesis has been extensively studied, effective treatment of HD has yet to be developed. Therapeutic discovery research in HD has been reported using yeast, cells derived from transgenic animal models and HD patients, and induced pluripotent stem cells from patients. A transgenic nonhuman primate model of HD (HD monkey) shows neuropathological, behavioral, and molecular changes similar to an HD patient. In addition, neural progenitor cells (NPCs) derived from HD monkeys can be maintained in culture and differentiated to neural cells with distinct HD cellular phenotypes including the formation of mHTT aggregates, intranuclear inclusions, and increased susceptibility to oxidative stress. Here, we evaluated the potential application of HD monkey NPCs and neural cells as an in vitro model for HD drug discovery research.

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