scholarly journals Genome destabilization under stress in cells of the prefrontal cortex, hippocampus and bone marrow of rats with contrast excitability of the nervous system

2020 ◽  
Vol 18 (4) ◽  
pp. 457-466
Author(s):  
Marina B. Pavlova ◽  
Alexander I. Vaido ◽  
Diana A.-A. Khlebaeva ◽  
Eugene V. Daev ◽  
Natalia A. Dyuzhikova

We studied changes in the stability of the genome in cells of two brain regions (prefrontal cortex and hippocampus), as well as in the bone marrow of rats with a hereditary high and low thresholds of excitability of the nervous system (strains HT and LT, respectively) after prolonged exposure with emotional-pain stressor. To study the reactivity of the brain cells genome, phosphorylated histone -H2AX (-H2AX phospho Ser139) was used. The level of mitotic disturbances in bone marrow cells was also assessed. Between the animals of the control groups, there were no interstrain differences in the studied parameters. Stress exposure increases the immunoreactivity to -H2AX phospho Ser139 of the prefrontal cortex cells and the level of chromosomal aberrations in bone marrow cells in animals of both strains. In cells of the dentate gyrus of the hippocampus, a specific increase in immunoreactivity to -H2AX phospho Ser139 was revealed in rats of the low-excitable HT strain. The relationship between the reaction of cells of this zone of hippocampus to the stressor exposure with the hereditary level of excitability of the nervous system of animals is discussed.

2011 ◽  
Vol 4 (1) ◽  
pp. 54-59 ◽  
Author(s):  
Humberto G. Rodrigues ◽  
Nilson G. Rodrigues ◽  
Mariana Ferreira Pereira de Araujo ◽  
Hisao Nishijo ◽  
Tales A. Aversi-Ferreira

2013 ◽  
Vol 6 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Nazia Nazam ◽  
Mohammad Iqbal Lone ◽  
Sibhghatulla Shaikh ◽  
Waseem Ahmad

Abstract The possible genotoxic activity of Dichlorvos (2,2-Dichlorovinyl-O,O-dimethyl phosphate/DDVP, CAS No. 62-73-7), an organophosphorus insecticide was investigated employing three cytogenetic end points, i.e. micronucleus (MN) assay, mitotic indices (MI) and chromosome abberation (CA) analysis in vivo. The assays were carried out in hematopoietic bone marrow cells of Mus musculus at concentrations of 10, 20 and 30% of LD50 for intraperitoneal (ip) administration, corresponding to 0.06, 0.08 and 0.13 mg/kg Bwt, respectively. The normal control group received single ip dose of distilled water (2 ml/100 g Bwt), while animals of the positive group were injected with cyclophosphamide, a model mutagen (40 mg/kg Bwt) under identical conditions. The animals were sacrificed 24, 48 and 72 hrs post treatment. Under the present experimental conditions, there was no evidence of significant increase of MN frequencies at any dose or sampling time in polychromatic (PCE) and normochromatic (NCE) erythrocytes. The PCE/NCE ratio was not notably affected; however, a slight depression in prolonged exposure (48, 72 hr) intervals and a slight increase at the 24 hr interval were observed. Cells with various structural chromosome aberrations were noted but no significant (p<0.05; Man-Whitney U-test) differences in the frequencies of CA or mitotic indices (p<0.05; X2 test) were observed between Dichlorvos treated groups and the normal control group at doses or time intervals used. The results of the present investigation reflects a negative in vivo genotoxic potential of Dichlorvos at sublethal doses in bone marrow cells. Further studies are underway to confirm the presence or absence of genotoxic activity since compounds negative in genotoxic evaluation are susceptible of being carcinogens triggering cancer by genotoxic or non-genotoxic mechanisms.


2002 ◽  
Vol 22 (7) ◽  
pp. 783-791 ◽  
Author(s):  
Tapas Kumar Makar ◽  
Susan Wilt ◽  
Zhongyun Dong ◽  
Paul Fishman ◽  
M. Maral Mouradian ◽  
...  

It is known that cadmium ions have the property of accumulating in cells, leading to disturbances in their metabolism. The purpose of this work was to assess the cytotoxicity effects and degree of DNA damage in bone marrow cell culture from the femur of rats during prolonged cultivation in a medium containing small doses of cadmium ions – 0.1; 0.5; 1.0; 10 μM/liter of culture medium. The extent of cell adhesion and their morphology, culture density, cell membrane integrity, and the number of apoptotic cells were analyzed. The extent of DNA damage was assessed by the number of micronuclei, fragmentation of nuclear DNA in cells. It has been shown that prolonged exposure to cadmium ions in concentrations of 0.1; 0.5; 1.0 and 10 μM/L on bone marrow cells in vitro has a pronounced cytotoxic effect, and the degree of damage depends on the exposure time and the concentration of the toxicant. Exposure to cadmium for 30 days at a concentration of 0.1 and 0.5 μM/L leads to a low decrease in cell adhesion, does not lead to their average size change and serious damage to the plasma membrane. Exposure to cadmium for 30 days at a concentration of 0.1 and 0.5 μM/L leads to an increase in the number of cells in the early apoptosis stage (by 11% and 15% respectively), which is reversible and does not affect the fragmentation of nuclear DNA. Exposure to cadmium in concentrations of 1.0 and 10.0 μM leads to a significant reduction in cell adhesion, a decrease in the average cell size by 1.3 and 1.8 times, respectively, to severe damage of the cell membrane. With an increase in the concentration of Cd2+ to 1.0 and 10.0 μM/L, the number of cells with an intact membrane decreases by 27% and 50%, respectively. When exposed to cadmium ions at a concentration of 1.0 and 10.0 μM/L the proportion of cells found at both early and late stages of apoptosis increases on the 10 and 4 days of observation, respectively. By 30 days of observation it has been shown, that exposure to cadmium at a concentration of 1.0 and 10.0 μM leads to a significant increase in the number of cells in the irreversible stage of late apoptosis. It has been found, that prolonged exposure to cadmium ions in concentrations of 0.5; 1.0 and 10 μM/L per bone marrow cells in vitro has a clear genotoxic effect: the number of micronuclei and the degree of DNA fragmentation increase.


Blood ◽  
2005 ◽  
Vol 106 (7) ◽  
pp. 2259-2268 ◽  
Author(s):  
Renata Sano ◽  
Alessandra Tessitore ◽  
Angela Ingrassia ◽  
Alessandra d'Azzo

AbstractBone marrow cells (BMCs) could correct some pathologic conditions of the central nervous system (CNS) if these cells would effectively repopulate the brain. One such condition is GM1-gangliosidosis, a neurodegenerative glycosphingolipidosis due to deficiency of lysosomal β-galactosidase (β-gal). In this disease, abnormal build up of GM1-ganglioside in the endoplasmic reticulum of brain cells results in calcium imbalance, induction of an unfolded protein response (UPR), and neuronal apoptosis. These processes are accompanied by the activation/proliferation of microglia and the production of inflammatory cytokines. Here we demonstrate that local neuroinflammation promotes the selective activation of chemokines, such as stromal-cell-derived factor 1 (SDF-1), macrophage inflammatory protein 1-α (MIP-1α), and MIP-1β, which chemoattract genetically modified BMCs into the CNS. Mice that underwent bone marrow transplantation showed increased β-gal activity in different brain regions and reduced lysosomal storage. Decreased production of chemokines and effectors of the UPR as well as restoration of neurologic functions accompanied this phenotypic reversion. Our results suggest that β-gal-expressing bone marrow (BM)-derived cells selectively migrate to the CNS under a gradient of chemokines and become a source of correcting enzyme to deficient neurons. Thus, a disease condition such as GM1-gangliosidosis, which is characterized by neurodegeneration and neuroinflammation, may influence the response of the CNS to ex vivo gene therapy.


2006 ◽  
Vol 54 (S 1) ◽  
Author(s):  
C Stamm ◽  
YH Choi ◽  
A Liebold ◽  
HD Kleine ◽  
S Dunkelmann ◽  
...  

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