Navegando por Assunto "Neuroglia"

Agora exibindo 1 - 6 de 6

Acesso aberto (Open Access)
Análise do efeito tóxico e alterações transcriptomicas de células neuronais e gliais após exposição ao fluoreto
(Universidade Federal do Pará, 2019-05-23) GOMES, Bruna Puty Silva; OLIVEIRA, Edivaldo Herculano Corrêa de; http://lattes.cnpq.br/0094007714707651; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
Despite being widely used in dentistry for dental carie control, in high amounts fluoride may be associated with side effects of which the best known is dental fluorosis. In addition, studies suggest that even at low concentrations fluoride may exerts toxicity leading to damage on CNS. Functional toxicogenomics analysis of gene profile after exposure to contaminants has been used as a tool for the identification of biomarkers of exposure, as well as for the identification of signaling pathways that may be used for treatment and / or prevention of damage caused by the toxicity of certain compounds. As the molecular mechanism of fluoride toxicity still unknow, analysis of F chronic exposure on gene expression profile of CNS cells are necessary. Here we aimed to show the effect of fluoride exposure of plasma concentration founded on population that used to be exposed to fluoridated drink water, on the main CNS cells. In this way, we have used human cell lineage IMR-32 (neurons) and U87 (glial cells) to analyze parameter of viability, morphology and cell metabolism, ATP-synthesis, oxidative stress, DNA damage and global gene expression profile after 10 days exposure. Our results have shown that fluoride does not induce changes in IMR-32 cells. On the other hand, it induces cell death by necrosis, increased metabolism, decrease in ATP and GSH / GSSG in U87 cells and DNA fragmentation. The U87 gene expression profile is differentially altered after fluoride exposure, decreasing 1735 genes and an increasing expression of 1047 genes after exposure to 0.095μg / mL and decreasing of 1863 gene expression and increasing of 1023 expression after exposure to 0.22μg / mL. We also highlighted the major molecular pathways altered after exposure, such as the signaling pathway TNF-alpha via NFK-B and mitochondrial process. We also showed genes with significant importance biology (hub genes) such as the genes PTGES3, EP300, CYP1B1, RPS27A. Our results suggests that glial cell are affected by fluorides exposure and mitochondria has a major role on the mechanism of fluoride toxicity.
Acesso aberto (Open Access)
Citoproteção do ácido kójico (AK) na morte induzida por LPS em células de Muller de retina de embrião de galinha
(Universidade Federal do Pará, 2017-12-07) CARVALHO, Giselle Cristina Brasil; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
5-Hydroxy-2-hydroxymethyl-γ-pyrone (AK), a known inhibitor of tyrosinase, an enzyme important for melanin synthesis and therefore used for pigmentation disorders. AK also promotes significant activation of macrophages and promotes cytoplasmic accumulation of reactive oxygen species (ROS), suggesting its role as a potentiator of the immune system and microbicide. There is no work in literature that shows the action of AK in the central nervous system (CNS) as a cellular activator and its possible protective role against infections. To test this hypothesis, it use retinal Muller glia which have similar properties to those of macrophages. Therefore, the present work evaluates the action of AK as a possible protective role in LPS-induced cell death in culture of glial cells from chicken embryos. Cultures enriched with glial cells were treated with AK (10, 25, 50 and 100 μM) and LPS (0.1, 10, 100, and 500 ng / ml) for 24 hours. After treatment, the cells did not show AK-treated cytotoxicity; however, treated with LPS, cell death occurred in a dose-dependent manner. We verified the accumulation of EROs in groups treated with AK (100 μM) and LPS (100 and 500 ng / ml). Cultures co-treated with AK and LPS in the same concentrations there was a reduction of accumulation of EROs. AK was also able to inhibit the activity of antioxidant enzymes, (catalase and Superoxide dismutase) and glutathione levels, while LPS produces an increase in the activity of these antixodants. AK was able to inhibit the antioxidant enzymes and glutathione from the increase induced by LPS. These data show that AK promotes the modulation of oxidative and antioxidative balance as a possible protective mechanism in the cell death produced by LPS in Müller's Glia enriched cells.
Acesso aberto (Open Access)
Efeitos protetores da prolactina em cultivo glial de córtex de ratos expostos ao metilmercúrio
(Universidade Federal do Pará, 2008-04-04) SANTOS, Andréa Cristina Monteiro dos; DINIZ, Domingos Luiz Wanderley Picanço; http://lattes.cnpq.br/9601463988942971
Methylmercury (MeHg) is a compound highly neurotoxic and its degenerative mechanisms are not very clear yet. In Central Nervous System, MeHg is mostly uptake by astrocytes, decreasing neuronal exposition. Studies demonstrated that prolactin (PRL) has mitogenic effects on astrocytes and it can regulate pro-inflammatories cytokines expression. The aim of this work was to verify the protective effects of PRL on disturbs provoked by MeHg on cellular viability, morphology, GFAP (glial fibrillary acidic protein) expression, mitogenesis and release of interleukin-1β in glia primary culture of cerebral cortex of newborn rats, with astrocytes in focus. Glia primary culture were exposed to differents concentrations of MeHg (0,1, 1, 5 e 10 μM) in differents time intervals (2, 4, 6, 18 e 24 h) in medium with fetal bovine serum 10%. Results demonstrated progressive decreasing of 20% e 62% on cellular viability after exposed to 5 e 10 μM MeHg for 24 h, respectively, by MTT [3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and disturbs in the GFAP expression and distribution. Differents concentrations of PRL (0.1, 1 e 10 nM) were added in free serum medium to evaluate it proliferative action. This was confirmed by mitogenesis induction around 4.5x in 18h at 10 mM PRL. In this conditions (free serum) were evaluated the effects of co-treatment of 1 nM PRL + 5 μM MeHg on cellular viability, morphology, GFAP expression, mitotic index and release of IL-1β. PRL attenuated disturbs caused by MeHg, increasing viability in 33%, GFAP expression, cellular proliferation (4x), and attenuating morphologic alterations like nuclear picnosis and lisis. These findings prove that PRL can act like a cytoprotective agent in primary culture of glia, particularly in astrocytes, in addition to its mitogenic effects.
Acesso aberto (Open Access)
Exposição à concentração subletal de metilmercúrio: genotoxicidade e alterações na proliferação celular
(Universidade Federal do Pará, 2015-04-01) MALAQUIAS, Allan Costa; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Mercury is a metal that stands out from the rest for present liquid under normal temperature and pressure. This xenobiotic is the largest source of pollution in many parts of the world and has been characterized toxic to the central nervous system (CNS). After dumping in liquid form directly into soil and riverbed, this heavy metal complex with various organic elements or it is converted to methylmercury (MeHg) by aquatic microbiota. The MeHg can move up the food chain, an event known as biomagnification, which directly affects human life. Thereby, the Amazon stands out for having all the components necessary for the maintenance of biogeochemical cycle of mercury as well as populations chronically exposed with this heavy metal. And this metal is considered a public health problem. It is well known that this xenobiotic after acute exposure to high doses promotes disorders related to the emergence of degenerative processes in the CNS, however, the effects at low concentrations are not yet fully described. Despite this cell type play an important role in the mercury intoxication process, the role of this metal on glial cells is not well known, especially on the genome and cell proliferation. Thus, this study aimed to evaluate the effect of exposure to this xenobiotic at low concentration on DNA and cell proliferation in C6 glial lineage cells. The biochemical (mitochondrial activity - measured by MTT assay -) and morphofunctional evaluations (membrane integrity - measured by the assay with dyes and AA BE -) confirmed the absence of cell death after exposure to heavy metals in a concentration of 3 μM for 24 hours. Even without causing cell death processes, the treatment with sublethal concentration of MeHg that was able to significantly increase the levels of markers of genotoxicity (DNA fragmentation, micronuclei, nuclear nucleoplasmic bridges and nuclear bud). At the same time, it was possible to observe a change in the cell cycle by increasing the mitotic index and a change in the cell cycle profile with increased cell population in S and G2 / M phases, suggesting an arrest cell cycle arrest. This change in cell cycle caused by MeHg exposure was followed by number of viable cells and cell confluence decrease, 24 hours after the withdrawal of MeHg of culture medium. The C6 cell line culture in addition showed an increase on doubling time parameter. This study demonstrates for the first time exposure to methylmercury low and sublethal concentration can promote genotoxic events and disturbances in cell proliferation in glial cell origin.
Acesso aberto (Open Access)
Ruptura total do tendão de Aquiles induz resposta inflamatória e ativação glial na medula espinhal de camundongos
(Universidade Federal do Pará, 2022-05) PAULA, Diego Rodrigues de; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247
Achilles tendon rupture is a common accident that affects both professional and recreational athletes. Acute and chronic pain are commonly seen in patients after rupture, usually associated with local inflammatory activation. The factors leading to hyperalgesia in symptomatic patients are poorly understood. Evidence suggests that Achilles tendon rupture is not restricted to tissue changes, but is able to evoke changes in the central nervous system (CNS). This study aimed to evaluate the impact of Achilles tendon rupture on the biochemical and histological profile in the spinal cord (L5) and on the nociceptive response in a murine model. The animals after Achilles tendon tenotomy surgery were divided into two groups: control (without rupture) and Rupture (tenotomized). Mechanical sensitivity test (von Frey) was assessed on the 7th and 14th day post-tenotomy (dpt). Glial reactivity was assessed by immunohistochemistry for microglia (IBA-1) and astrocytes (GFAP). Inflammatory activation was assessed by immunofluorescence for NOS-2 and COX2 at 7th and 14th dpt. We show, by the mechanical sensitivity test, an increase in the algesic response in the ipsilateral paw of the ruptured group on the 7th and 14th dpt when compared to the control group. This phenomenon was accompanied by hyperactivation of astrocytes and microglia in sensory processing areas of the L5 spinal cord, predominantly on the ipsilateral side to the tendon injury. We show inflammatory activation by expression of COX-2 and NOS-2, exclusively in the 14th dpt. These data were supported by biochemical findings that demonstrated significant nitrite levels increase in the lumbar spinal cord of animals submitted to Achilles tendon rupture at 7 and 14 dpt. The present study demonstrated for the first time that complete rupture of the Achilles tendon induces a neuroinflammatory response associated with glial activation in the spinal cord (L5) of mice.
Acesso aberto (Open Access)
Therapeutic concentration of morphine reduces oxidative stress in glioma cell line
(2014-05) ALMEIDA, Mauro Brito de; MALAQUIAS, Allan Costa; NASCIMENTO, José Luiz Martins do; OLIVEIRA, Karen Renata Matos; SILVA, Anderson Manoel Herculano Oliveira da; CRESPO LÓPEZ, Maria Elena
Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2) but partially prevented lipid peroxidation caused by 0.0025% H2O2) (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2), opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.