Exposure Of Neural Stem Cells Research Articles

Functional Consequences of Radiation-Induced Oxidative Stress in Cultured Neural Stem Cells and the Brain Exposed to Charged Particle Irradiation

Redox homeostasis is critical in regulating the fate and function of multipotent cells in the central nervous system (CNS). Here, we investigated whether low dose charged particle irradiation could elicit oxidative stress in neural stem and precursor cells and whether radiation-induced changes in redox metabolism would coincide with cognitive impairment. Low doses (<1 Gy) of charged particles caused an acute and persistent oxidative stress. Early after (<1 week) irradiation, increased levels of reactive oxygen and nitrogen species were generally dose responsive, but were less dependent on dose weeks to months thereafter. Exposure to ion fluences resulting in less than one ion traversal per cell was sufficient to elicit radiation-induced oxidative stress. Whole body irradiation triggered a compensatory response in the rodent brain that led to a significant increase in antioxidant capacity 2 weeks following exposure, before returning to background levels at week 4. Low dose irradiation was also found to significantly impair novel object recognition in mice 2 and 12 weeks following irradiation. Data provide evidence that acute exposure of neural stem cells and the CNS to very low doses and fluences of charged particles can elicit a persisting oxidative stress lasting weeks to months that is associated with impaired cognition. Exposure to low doses of charged particles causes a persistent oxidative stress and cognitive impairment over protracted times. Data suggest that astronauts subjected to space radiation may develop a heightened risk for mission critical performance decrements in space, along with a risk of developing long-term neurocognitive sequelae.

Analysis of Epigenetic Factors in Mouse Embryonic Neural Stem Cells Exposed to Hyperglycemia

BackgroundMaternal diabetes alters gene expression leading to neural tube defects (NTDs) in the developing brain. The mechanistic pathways that deregulate the gene expression remain unknown. It is hypothesized that exposure of neural stem cells (NSCs) to high glucose/hyperglycemia results in activation of epigenetic mechanisms which alter gene expression and cell fate during brain development.Methods and FindingsNSCs were isolated from normal pregnancy and streptozotocin induced-diabetic pregnancy and cultured in physiological glucose. In order to examine hyperglycemia induced epigenetic changes in NSCs, chromatin reorganization, global histone status at lysine 9 residue of histone H3 (acetylation and trimethylation) and global DNA methylation were examined and found to be altered by hyperglycemia. In NSCs, hyperglycemia increased the expression of Dcx (Doublecortin) and Pafah1b1 (Platelet activating factor acetyl hydrolase, isoform 1b, subunit 1) proteins concomitant with decreased expression of four microRNAs (mmu-miR-200a, mmu-miR-200b, mmu-miR-466a-3p and mmu-miR-466 d-3p) predicted to target these genes. Knockdown of specific microRNAs in NSCs resulted in increased expression of Dcx and Pafah1b1 proteins confirming target prediction and altered NSC fate by increasing the expression of neuronal and glial lineage markers.Conclusion/InterpretationThis study revealed that hyperglycemia alters the epigenetic mechanisms in NSCs, resulting in altered expression of some development control genes which may form the basis for the NTDs. Since epigenetic changes are reversible, they may be valuable therapeutic targets in order to improve fetal outcomes in diabetic pregnancy.

Metabolic state alteration of neural stem cells controls FAS-mediated apoptosis and neurogenesis

Metabolic stress causes an increased Fas-FasL (receptor-ligand pair) expression in Neural Stem Cells (NSCs) leading to Fas-induced apoptosis. In this study, we discuss the exposure of NSCs to different metabolic treatments that provoke cellular stress responses. We demonstrate that challenging cultured NSCs to ethanol (ETOH) increased cellular death via Fas-mediated apoptosis. Moreover, we establish that NSCs cultured under low lipid conditions, in which they were deprived of essential fatty acids, demonstrated increased cellular survival rates suggesting an increased ability for these lipid-starved cells to endure a stressed environment. This was further confirmed by exposing NSCs to low glucose levels and observing a decrease in percent death in low lipid NSCs. When stressed, NSCs have increased reactive oxygen levels and are susceptible to apoptosis. These findings indicate that under starved and stressed conditions, and in the presence of Fas Ligand (FasL), NSCs pursue fatty acid oxidation by burning fat as fuel. This may be the key to better understand the metabolic states of brain tumors and the characteristics of cancer.

Effects of Ionizing Radiation on Neural Precursor Cells (P02.023)

Objective: To elucidate cellular and molecular changes associated with the exposure of neural stem cells (NSCs) to high and low doses of ionizing radiation. Background Damage to normal human brain cells from targeted exposure to ionizing radiation may occur during the course of cancer radiotherapy or from accidental exposure. Delayed effects may complicate the acute immediate effects, and in particular have been associated with neurodegeneration and cognitive decline. These delayed effects may arise from the slow death of irradiated cells, damage to cells that survive the radiation exposure, or from negative effects on normal cell replenishment of non-targeted brain cells from neural stem cells. Design/Methods: Subventricular zone (SVZ) neural precursors isolated from newborn mouse pups were analyzed for survival, proliferation and differentiation after exposure to low and high doses of γ rays (range from 0 to 8 Gy). Results: The ability of the neurospheres to differentiate into astroglia, neurons, and oligodendroglia was assessed in the studied groups 8 days after irradiation. There were no significant changes in the neurosphere differentiation ability between the irradiated cells and controls (p>0.05). Surprisingly, the number of neurospheres formed showed no significant change from control, up to 8 Gy of γ irradiation. Meanwhile, the size of the spheres increased slightly at low doses without any significant change(0.4 or 0.5 Gy), and decreased dramatically at 8 Gy (p Conclusions: Our data suggest that neural stem cells/neural precursors derived from the SVZ are resistant to ionizing irradiation. However, their proliferation is inhibited subsequent to exposure to ionizing radiation. Supported by: Start up fund. Disclosure: Dr. Chen has nothing to disclose. Dr. Levison has nothing to disclose. Dr. De Toledo has nothing to disclose. Dr. Azzam has nothing to disclose. Dr. Souayah has received personal compensation for activities with Walgreens as a consultant. Dr. Souayah has received research support from Talecris.

Effects of Ionizing Radiation on Neural Precursor Cells (IN8-1.008)

Objective: To elucidate cellular and molecular changes associated with the exposure of neural stem cells (NSCs) to high and low doses of ionizing radiation. Background Damage to normal human brain cells from targeted exposure to ionizing radiation may occur during the course of cancer radiotherapy or from accidental exposure. Delayed effects may complicate the acute immediate effects, and in particular have been associated with neurodegeneration and cognitive decline. These delayed effects may arise from the slow death of irradiated cells, damage to cells that survive the radiation exposure, or from negative effects on normal cell replenishment of non-targeted brain cells from neural stem cells. Design/Methods: Subventricular zone (SVZ) neural precursors isolated from newborn mouse pups were analyzed for survival, proliferation and differentiation after exposure to low and high doses of γ rays (range from 0 to 8 Gy). Results: The ability of the neurospheres to differentiate into astroglia, neurons, and oligodendroglia was assessed in the studied groups 8 days after irradiation. There were no significant changes in the neurosphere differentiation ability between the irradiated cells and controls (p>0.05). Surprisingly, the number of neurospheres formed showed no significant change from control, up to 8 Gy of γ irradiation. Meanwhile, the size of the spheres increased slightly at low doses without any significant change(0.4 or 0.5 Gy), and decreased dramatically at 8 Gy (p Conclusions: Our data suggest that neural stem cells/neural precursors derived from the SVZ are resistant to ionizing irradiation. However, their proliferation is inhibited subsequent to exposure to ionizing radiation. Supported by: Start up fund. Disclosure: Dr. Chen has nothing to disclose. Dr. Levison has nothing to disclose. Dr. De Toledo has nothing to disclose. Dr. Azzam has nothing to disclose. Dr. Souayah has received personal compensation for activities with Walgreens as a consultant. Dr. Souayah has received research support from Talecris.

Protective effects of a Rhodiola crenulata extract and salidroside on hippocampal neurogenesis against streptozotocin-induced neural injury in the rat.

Previously we have demonstrated that a Rhodiola crenulata extract (RCE), containing a potent antioxidant salidroside, promotes neurogenesis in the hippocampus of depressive rats. The current study was designed to further investigate the protective effect of the RCE on neurogenesis in a rat model of Alzheimer's disease (AD) induced by an intracerebroventricular injection of streptozotocin (STZ), and to determine whether this neuroprotective effect is induced by the antioxidative activity of salidroside. Our results showed that pretreatment with the RCE significantly improved the impaired neurogenesis and simultaneously reduced the oxidative stress in the hippocampus of AD rats. In vitro studies revealed that (1) exposure of neural stem cells (NSCs) from the hippocampus to STZ strikingly increased intracellular reactive oxygen species (ROS) levels, induced cell death and perturbed cell proliferation and differentiation, (2) hydrogen peroxide induced similar cellular activities as STZ, (3) pre-incubation of STZ-treated NSCs with catalase, an antioxidant, suppressed all these cellular activities induced by STZ, and (4) likewise, pre-incubation of STZ-treated NSCs with salidroside, also an antioxidant, suppressed all these activities as catalase: reduction of ROS levels and NSC death with simultaneous increases in proliferation and differentiation. Our findings indicated that the RCE improved the impaired hippocampal neurogenesis in the rat model of AD through protecting NSCs by its main ingredient salidroside which scavenged intracellular ROS.