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Sample records for microglia antioxidative systems

  1. Microglia antioxidant systems and redox signaling

    DEFF Research Database (Denmark)

    Vilhardt, F; Haslund-Vinding, J; Jaquet, V

    2017-01-01

    For many years microglia, the resident CNS macrophages, have been considered only in the context of pathology, but microglia are also glia cells with important physiological functions. Microglia-derived oxidant production by NADPH oxidase (NOX2) is implicated in many CNS disorders. Oxidants don...

  2. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells

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    Iva eBozic

    2015-09-01

    Full Text Available Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate possesses anti-inflammatory effects. Here, the effects of benfotiamine on the pro-oxidative component of activity of LPS-stimulated BV-2 cells were investigated. The activation of microglia was accompanied by upregulation of intracellular antioxidative defense, which was further promoted in the presence of benfotiamine. Namely, activated microglia exposed to non-cytotoxic doses of benfotiamine showed increased levels and activities of hydrogen peroxide- and superoxide-removing enzymes – catalase and glutathione system, and superoxide dismutase. In addition, benfotiamine showed the capacity to directly scavenge superoxide radical anion. As a consequence, benfotiamine suppressed the activation of microglia and provoked a decrease in NO and •O2- production and lipid peroxidation. In conclusion, benfotiamine might silence pro-oxidative activity of microglia to alleviate/prevent oxidative damage of neighboring CNS cells.

  3. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells.

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    Bozic, Iva; Savic, Danijela; Stevanovic, Ivana; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate) possesses anti-inflammatory effects. Here, the effects of benfotiamine on the pro-oxidative component of activity of LPS-stimulated BV-2 cells were investigated. The activation of microglia was accompanied by upregulation of intracellular antioxidative defense, which was further promoted in the presence of benfotiamine. Namely, activated microglia exposed to non-cytotoxic doses of benfotiamine showed increased levels and activities of hydrogen peroxide- and superoxide-removing enzymes-catalase and glutathione system, and superoxide dismutase. In addition, benfotiamine showed the capacity to directly scavenge superoxide radical anion. As a consequence, benfotiamine suppressed the activation of microglia and provoked a decrease in NO and (·)O(-) 2 production and lipid peroxidation. In conclusion, benfotiamine might silence pro-oxidative activity of microglia to alleviate/prevent oxidative damage of neighboring CNS cells.

  4. Benfotiamine upregulates antioxidative system in activated BV-2 microglia cells

    OpenAIRE

    Bozic, Iva; Savic, Danijela; Stevanovic, Ivana; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Chronic microglial activation and resulting sustained neuroinflammatory reaction are generally associated with neurodegeneration. Activated microglia acquires proinflammatory cellular profile that generates oxidative burst. Their persistent activation exacerbates inflammation, which damages healthy neurons via cytotoxic mediators, such as superoxide radical anion and nitric oxide. In our recent study, we have shown that benfotiamine (S-benzoylthiamine O-monophosphate) possesses anti-inflammat...

  5. The role of glucocorticoid, interleukin-1β, and antioxidants in prenatal stress effects on embryonic microglia.

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    Bittle, Jada; Stevens, Hanna E

    2018-02-16

    Maternal stress during pregnancy is associated with an increased risk of psychopathology in offspring. Resident immune cells of the brain, microglia, may be mediators of prenatal stress and altered neurodevelopment. Here, we demonstrate that neither the exogenous pro-inflammatory cytokine, interleukin-1β (IL-1β), nor the glucocorticoid hormone, corticosterone, recapitulated the full effects of prenatal stress on the morphology of microglial cells in the cortical plate of embryonic mice; IL-1β effects showed greater similarity to prenatal stress effects on microglia. Unexpectedly, oil vehicle alone, which has antioxidant properties, moderated the effects of prenatal stress on microglia. Microglia changes with prenatal stress were also sensitive to the antioxidant, N-acetylcysteine, suggesting redox dysregulation as a mechanism of prenatal stress.

  6. Nutrients, Microglia Aging, and Brain Aging

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    Zhou Wu

    2016-01-01

    Full Text Available As the life expectancy continues to increase, the cognitive decline associated with Alzheimer’s disease (AD becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of “microglia aging.” This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  7. Nutrients, Microglia Aging, and Brain Aging.

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    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  8. Microglia - insights into immune system structure, function, and reactivity in the central nervous system

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    Wirenfeldt, Martin; Babcock, Alicia A; Vinters, Harry V

    2011-01-01

    Microglia are essential cellular components of a well-functioning central nervous system (CNS). The development and establishment of the microglial population differs from the other major cell populations in the CNS i.e. neurons and macroglia (astrocytes and oligodendrocytes). This different onto...

  9. Immunosenescence of microglia and macrophages: impact on the ageing central nervous system.

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    Rawji, Khalil S; Mishra, Manoj K; Michaels, Nathan J; Rivest, Serge; Stys, Peter K; Yong, V Wee

    2016-03-01

    Ageing of the central nervous system results in a loss of both grey and white matter, leading to cognitive decline. Additional injury to both the grey and white matter is documented in many neurological disorders with ageing, including Alzheimer's disease, traumatic brain and spinal cord injury, stroke, and multiple sclerosis. Accompanying neuronal and glial damage is an inflammatory response consisting of activated macrophages and microglia, innate immune cells demonstrated to be both beneficial and detrimental in neurological repair. This article will propose the following: (i) infiltrating macrophages age differently from central nervous system-intrinsic microglia; (ii) several mechanisms underlie the differential ageing process of these two distinct cell types; and (iii) therapeutic strategies that selectively target these diverse mechanisms may rejuvenate macrophages and microglia for repair in the ageing central nervous system. Most responses of macrophages are diminished with senescence, but activated microglia increase their expression of pro-inflammatory cytokines while diminishing chemotactic and phagocytic activities. The senescence of macrophages and microglia has a negative impact on several neurological diseases, and the mechanisms underlying their age-dependent phenotypic changes vary from extrinsic microenvironmental changes to intrinsic changes in genomic integrity. We discuss the negative effects of age on neurological diseases, examine the response of senescent macrophages and microglia in these conditions, and propose a theoretical framework of therapeutic strategies that target the different mechanisms contributing to the ageing phenotype in these two distinct cell types. Rejuvenation of ageing macrophage/microglia may preserve neurological integrity and promote regeneration in the ageing central nervous system. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions

  10. Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells.

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    Foresti, Roberta; Bains, Sandip K; Pitchumony, Tamil Selvi; de Castro Brás, Lisandra E; Drago, Filippo; Dubois-Randé, Jean-Luc; Bucolo, Claudio; Motterlini, Roberto

    2013-10-01

    The nuclear factor erythroid derived 2-related factor 2 (Nrf2) and the antioxidant protein heme oxygenase-1 (HO-1) are crucial components of the cellular stress response. These two systems work together to combat oxidative stress and inflammation and are attractive drug targets for counteracting different pathologies, including neuroinflammation. We aimed to identify the most effective Nrf2/HO-1 activators that modulate the inflammatory response in microglia cells. In the present study, we searched the literature and selected 56 compounds reported to activate Nrf2 or HO-1 and analyzed them for HO-1 induction at 6 and 24h and cytotoxicity in BV2 microglial cells in vitro. Approximately 20 compounds up-regulated HO-1 at the concentrations tested (5-20 μM) with carnosol, supercurcumin, cobalt protoporphyrin-IX and dimethyl fumarate exhibiting the best induction/low cytotoxicity profile. Up-regulation of HO-1 by some compounds resulted in increased cellular bilirubin levels but did not augment the expression of proteins involved in heme synthesis (ALAS 1) or biliverdin reductase. Bilirubin production by HO-1 inducers correlated with their potency in inhibiting nitrite production after challenge with interferon-γ (INF-γ) or lipopolysaccharide (LPS). The compounds down-regulated the inflammatory response (TNF-α, PGE2 and nitrite) more strongly in cells challenged with INF-γ than LPS, and silencing HO-1 or Nrf2 with shRNA differentially affected the levels of inflammatory markers. These findings indicate that some small activators of Nrf2/HO-1 are effective modulators of microglia inflammation and highlight the chemical scaffolds that can serve for the synthesis of potent new derivatives to counteract neuroinflammation and neurodegeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. The leech nervous system: a valuable model to study the microglia involvement in regenerative processes.

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    Le Marrec-Croq, Françoise; Drago, Francesco; Vizioli, Jacopo; Sautière, Pierre-Eric; Lefebvre, Christophe

    2013-01-01

    Microglia are intrinsic components of the central nervous system (CNS). During pathologies in mammals, inflammatory processes implicate the resident microglia and the infiltration of blood cells including macrophages. Functions of microglia appear to be complex as they exhibit both neuroprotective and neurotoxic effects during neuropathological conditions in vivo and in vitro. The medicinal leech Hirudo medicinalis is a well-known model in neurobiology due to its ability to naturally repair its CNS following injury. Considering the low infiltration of blood cells in this process, the leech CNS is studied to specify the activation mechanisms of only resident microglial cells. The microglia recruitment is known to be essential for the usual sprouting of injured axons and does not require any other glial cells. The present review will describe the questions which are addressed to understand the nerve repair. They will discuss the implication of leech factors in the microglial accumulation, the identification of nerve cells producing these molecules, and the study of different microglial subsets. Those questions aim to better understand the mechanisms of microglial cell recruitment and their crosstalk with damaged neurons. The study of this dialog is necessary to elucidate the balance of the inflammation leading to the leech CNS repair.

  12. The Leech Nervous System: A Valuable Model to Study the Microglia Involvement in Regenerative Processes

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    Françoise Le Marrec-Croq

    2013-01-01

    Full Text Available Microglia are intrinsic components of the central nervous system (CNS. During pathologies in mammals, inflammatory processes implicate the resident microglia and the infiltration of blood cells including macrophages. Functions of microglia appear to be complex as they exhibit both neuroprotective and neurotoxic effects during neuropathological conditions in vivo and in vitro. The medicinal leech Hirudo medicinalis is a well-known model in neurobiology due to its ability to naturally repair its CNS following injury. Considering the low infiltration of blood cells in this process, the leech CNS is studied to specify the activation mechanisms of only resident microglial cells. The microglia recruitment is known to be essential for the usual sprouting of injured axons and does not require any other glial cells. The present review will describe the questions which are addressed to understand the nerve repair. They will discuss the implication of leech factors in the microglial accumulation, the identification of nerve cells producing these molecules, and the study of different microglial subsets. Those questions aim to better understand the mechanisms of microglial cell recruitment and their crosstalk with damaged neurons. The study of this dialog is necessary to elucidate the balance of the inflammation leading to the leech CNS repair.

  13. Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia

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    Püntener Ursula

    2012-06-01

    Full Text Available Abstract Background Systemic infection leads to generation of inflammatory mediators that result in metabolic and behavioural changes. Repeated or chronic systemic inflammation leads to a state of innate immune tolerance: a protective mechanism against overactivity of the immune system. In this study, we investigated the immune adaptation of microglia and brain vascular endothelial cells in response to systemic inflammation or bacterial infection. Methods Mice were given repeated doses of lipopolysaccharide (LPS or a single injection of live Salmonella typhimurium. Inflammatory cytokines were measured in serum, spleen and brain, and microglial phenotype studied by immunohistochemistry. To assess priming of the innate immune response in the brain, mice were infected with Salmonella typhimurium and subsequently challenged with a focal unilateral intracerebral injection of LPS. Results Repeated systemic LPS challenges resulted in increased brain IL-1β, TNF-α and IL-12 levels, despite attenuated systemic cytokine production. Each LPS challenge induced significant changes in burrowing behaviour. In contrast, brain IL-1β and IL-12 levels in Salmonella typhimurium-infected mice increased over three weeks, with high interferon-γ levels in the circulation. Behavioural changes were only observed during the acute phase of the infection. Microglia and cerebral vasculature display an activated phenotype, and focal intracerebral injection of LPS four weeks after infection results in an exaggerated local inflammatory response when compared to non-infected mice. Conclusions These studies reveal that the innate immune cells in the brain do not become tolerant to systemic infection, but are primed instead. This may lead to prolonged and damaging cytokine production that may have a profound effect on the onset and/or progression of pre-existing neurodegenerative disease.

  14. Optimized isolation enables Ex vivo analysis of microglia from various central nervous system regions

    NARCIS (Netherlands)

    De Haas, Alexander H.; Boddeke, Hendricus W. G. M.; Brouwer, Nieske; Biber, Knut

    2007-01-01

    Ex vivo analysis is an accurate and convenient way to study in vivo microglia phenotype and function. However, current microglia isolation protocols for ex vivo analysis show many differences in isolation steps (perfusion, removal of meninges and blood vessels, mechanical dissociation, enzymatic

  15. Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge.

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    Norden, Diana M; Trojanowski, Paige J; Villanueva, Emmanuel; Navarro, Elisa; Godbout, Jonathan P

    2016-02-01

    Activation of the peripheral immune system elicits a coordinated response from the central nervous system. Key to this immune to brain communication is that glia, microglia, and astrocytes, interpret and propagate inflammatory signals in the brain that influence physiological and behavioral responses. One issue in glial biology is that morphological analysis alone is used to report on glial activation state. Therefore, our objective was to compare behavioral responses after in vivo immune (lipopolysaccharide, LPS) challenge to glial specific mRNA and morphological profiles. Here, LPS challenge induced an immediate but transient sickness response with decreased locomotion and social interaction. Corresponding with active sickness behavior (2-12 h), inflammatory cytokine mRNA expression was elevated in enriched microglia and astrocytes. Although proinflammatory cytokine expression in microglia peaked 2-4 h after LPS, astrocyte cytokine, and chemokine induction was delayed and peaked at 12 h. Morphological alterations in microglia (Iba-1(+)) and astrocytes (GFAP(+)), however, were undetected during this 2-12 h timeframe. Increased Iba-1 immunoreactivity and de-ramified microglia were evident 24 and 48 h after LPS but corresponded to the resolution phase of activation. Morphological alterations in astrocytes were undetected after LPS. Additionally, glial cytokine expression did not correlate with morphology after four repeated LPS injections. In fact, repeated LPS challenge was associated with immune and behavioral tolerance and a less inflammatory microglial profile compared with acute LPS challenge. Overall, induction of glial cytokine expression was sequential, aligned with active sickness behavior, and preceded increased Iba-1 or GFAP immunoreactivity after LPS challenge. © 2015 Wiley Periodicals, Inc.

  16. TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis

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    Renno, T; Krakowski, M; Piccirillo, C

    1995-01-01

    in the pathology of multiple sclerosis and its animal model experimental allergic encephalomyelitis (EAE). We used reverse transcriptase (RT)-PCR to study the kinetics, cellular source, and regulation of cytokine gene expression in the central nervous system (CNS) of SJL/J mice with myelin basic protein......, the majority of which were identified as microglia and macrophages by their Mac-1 phenotype. Microglia could be discriminated by their low expression of CD45. Incubation of freshly derived, adult microglia from normal, uninfiltrated, CNS with activated Th1 supernatant induced the production of TNF-alpha m...

  17. The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

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    Elisa Ridolfi

    2013-01-01

    Full Text Available In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD and frontotemporal lobar degeneration (FTLD have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS. They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

  18. The role of the innate immune system in Alzheimer's disease and frontotemporal lobar degeneration: an eye on microglia.

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    Ridolfi, Elisa; Barone, Cinzia; Scarpini, Elio; Galimberti, Daniela

    2013-01-01

    In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

  19. Intermittent hypoxia from obstructive sleep apnea may cause neuronal impairment and dysfunction in central nervous system: the potential roles played by microglia

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    Yang Q

    2013-08-01

    Full Text Available Qingchan Yang,1,* Yan Wang,2,* Jing Feng,2 Jie Cao,2 Baoyuan Chen2 1Graduate School of Tianjin Medical University, 2Respiratory Department, Tianjin Medical University General Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Abstract: Obstructive sleep apnea (OSA is a common condition characterized by repetitive episodes of complete (apnea or partial (hypopnea obstruction of the upper airway during sleep, resulting in oxygen desaturation and arousal from sleep. Intermittent hypoxia (IH resulting from OSA may cause structural neuron damage and dysfunction in the central nervous system (CNS. Clinically, it manifests as neurocognitive and behavioral deficits with oxidative stress and inflammatory impairment as its pathophysiological basis, which are mediated by microglia at the cellular level. Microglia are dominant proinflammatory cells in the CNS. They induce CNS oxidative stress and inflammation, mainly through mitochondria, reduced nicotinamide adenine dinucleotide phosphate oxidase, and the release of excitatory toxic neurotransmitters. The balance between neurotoxic versus protective and anti- versus proinflammatory microglial factors might determine the final roles of microglia after IH exposure from OSA. Microglia inflammatory impairments will continue and cascade persistently upon activation, ultimately resulting in clinically significant neuron damage and dysfunction in the CNS. In this review article, we summarize the mechanisms of structural neuron damage in the CNS and its concomitant dysfunction due to IH from OSA, and the potential roles played by microglia in this process. Keywords: intermittent hypoxia, obstructive sleep apnea, microglia, inflammation, apoptosis

  20. Modulation of Toll-like receptor-mediated activation of Microglia

    NARCIS (Netherlands)

    Putten, C. M.-T. van der

    2015-01-01

    Microglia are the resident macrophages of the central nervous system (CNS). Like other tissue macrophages, microglia have many different functions under physiological as well as pathological conditions. Microglia can contribute to the initiation, progression and resolution of disease processes and

  1. A homologous form of human interleukin 16 is implicated in microglia recruitment following nervous system injury in leech Hirudo medicinalis.

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    Croq, Françoise; Vizioli, Jacopo; Tuzova, Marina; Tahtouh, Muriel; Sautiere, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Cruikshank, William W; Pestel, Joel; Lefebvre, Christophe

    2010-11-01

    In contrast to mammals, the medicinal leech Hirudo medicinalis can completely repair its central nervous system (CNS) after injury. This invertebrate model offers unique opportunities to study the molecular and cellular basis of the CNS repair processes. When the leech CNS is injured, microglial cells migrate and accumulate at the site of lesion, a phenomenon known to be essential for the usual sprouting of injured axons. In the present study, we demonstrate that a new molecule, designated HmIL-16, having functional homologies with human interleukin-16 (IL-16), has chemotactic activity on leech microglial cells as observed using a gradient of human IL-16. Preincubation of microglial cells either with an anti-human IL-16 antibody or with anti-HmIL-16 antibody significantly reduced microglia migration induced by leech-conditioned medium. Functional homology was demonstrated further by the ability of HmIL-16 to promote human CD4+ T cell migration which was inhibited by antibody against human IL-16, an IL-16 antagonist peptide or soluble CD4. Immunohistochemistry of leech CNS indicates that HmIL-16 protein present in the neurons is rapidly transported and stored along the axonal processes to promote the recruitment of microglial cells to the injured axons. To our knowledge, this is the first identification of a functional interleukin-16 homologue in invertebrate CNS. The ability of HmIL-16 to recruit microglial cells to sites of CNS injury suggests a role for HmIL-16 in the crosstalk between neurons and microglia in the leech CNS repair.

  2. Systemic antioxidants and skin health.

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    Nguyen, Gloria; Torres, Abel

    2012-09-01

    Most dermatologists agree that antioxidants help fight free radical damage and can help maintain healthy skin. They do so by affecting intracellular signaling pathways involved in skin damage and protecting against photodamage, as well as preventing wrinkles and inflammation. In today's modern world of the rising nutraceutical industry, many people, in addition to applying topical skin care products, turn to supplementation of the nutrients missing in their diets by taking multivitamins or isolated, man-made nutraceuticals, in what is known as the Inside-Out approach to skin care. However, ingestion of large quantities of isolated, fragmented nutrients can be harmful and is a poor representation of the kind of nutrition that can be obtained from whole food sources. In this comprehensive review, it was found that few studies on oral antioxidants benefiting the skin have been done using whole foods, and that the vast majority of current research is focused on the study of compounds in isolation. However, the public stands to benefit greatly if more research were to be devoted toward the impact that physiologic doses of antioxidants (obtained from fruits, vegetables, and whole grains) can have on skin health, and on health in general.

  3. Phenolipids as antioxidants in emulsified systems

    DEFF Research Database (Denmark)

    Sørensen, Ann-Dorit Moltke; Bayrasy, Christelle; Laguerre, Mickäel

    Lipid oxidation is a major issue in foods containing LC PUFA and substantial efforts have been made to protect lipids against oxidation. Recent studies carried out with phenolipids (lipophilized phenolics) in emulsified systems have shown that increased lipophilicity did not necessarily lead...... antioxidant effect has been shown to be influenced by the specific phenolic compound and the type of emulsion. The overall aim for our work was to evaluate phenolipids with different lipophilicity as antioxidants in emulsified food. In the study presented here caffeic, ferulic and coumaric acid were selected...... along with their corresponding alkyl esters (C4-C20). The methods used to evaluate the antioxidative effect of the different phenolipids were the CAT assay (o/w emulsion), antioxidant assays (DPPH, Iron chelating and reducing power) and partitioning studies. Moreover, the results from the CAT assay...

  4. Oxidative Stress and Antioxidant System in Periodontitis

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    Wang, Yue; Andrukhov, Oleh; Rausch-Fan, Xiaohui

    2017-01-01

    Periodontitis is a common inflammatory disease, which is initiated by bacterial infection and subsequently progressed by aberrant host response. It can result in the destruction of teeth supporting tissues and have an influence on systemic health. When periodontitis occurs, reactive oxygen species, which are overproduced mostly by hyperactive neutrophils, could not be balanced by antioxidant defense system and cause tissues damage. This is characterized by increased metabolites of lipid peroxidation, DNA damage and protein damage. Local and systemic activities of antioxidants can also be influenced by periodontitis. Total antioxidant capacity, total oxidant status and oxidative stress index have been used to evaluate the oxidative stress associated with periodontitis. Studies have confirmed that inflammatory response in periodontitis is associated with an increased local and systemic oxidative stress and compromised antioxidant capacity. Our review focuses on increased oxidative stress in periodontal disease, specifically, on the relationship between the local and systemic biomarkers of oxidative stress and periodontitis and their association with the pathogenesis of periodontitis. Also, the relationship between periodontitis and systemic inflammation, and the effects of periodontal therapy on oxidative stress parameters will be discussed. PMID:29180965

  5. Microglia immunophenotyping in gliomas

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    Annovazzi, Laura; Mellai, Marta; Bovio, Enrica; Mazzetti, Samanta; Pollo, Bianca; Schiffer, Davide

    2018-01-01

    Microglia, once assimilated to peripheral macrophages, in gliomas has long been discussed and currently it is hypothesized to play a pro-tumor role in tumor progression. Uncertain between M1 and M2 polarization, it exchanges signals with glioma cells to create an immunosuppressive microenvironment and stimulates cell proliferation and migration. Four antibodies are currently used for microglia/macrophage identification in tissues that exhibit different cell forms and cell localization. The aim of the present work was to describe the distribution of the different cell forms and to deduce their significance on the basis of what is known on their function from the literature. Normal resting microglia, reactive microglia, intermediate and bumpy forms and macrophage-like cells can be distinguished by Iba1, CD68, CD16 and CD163 and further categorized by CD11b, CD45, c-MAF and CD98. The number of microglia/macrophages strongly increased from normal cortex and white matter to infiltrating and solid tumors. The ramified microglia accumulated in infiltration areas of both high- and low-grade gliomas, when hypertrophy and hyperplasia occur. In solid tumors, intermediate and bumpy forms prevailed and there is a large increase of macrophage-like cells in glioblastoma. The total number of microglia cells did not vary among the three grades of malignancy, but macrophage-like cells definitely prevailed in high-grade gliomas and frequently expressed CD45 and c-MAF. CD98+ cells were present. Microglia favors tumor progression, but many aspects suggest that the phagocytosing function is maintained. CD98+ cells can be the product of fusion, but also of phagocytosis. Microglia correlated with poorer survival in glioblastoma, when considering CD163+ cells, whereas it did not change prognosis in isocitrate dehydrogenase-mutant low grade gliomas. PMID:29399160

  6. Neuroprotective effect of curcumin against oxidative damage in BV-2 microglia and high intraocular pressure animal model.

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    Yue, Yan-Kun; Mo, Bin; Zhao, Jun; Yu, Ya-Jie; Liu, Lu; Yue, Chang-Li; Liu, Wu

    2014-10-01

    The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. In this study, we aim to evaluate the antioxidant effects of curcumin in BV-2 microglia oxidative damage and assess its neuroprotective effects in a chronic high IOP rat model. BV-2 microglia cell line was used in an in vitro study and Wistar rats were used in an in vivo study. Cultured BV-2 microglia cells were pretreated with 10, 1, or 0.1 μM curcumin for 1 h, and sustained oxidative stress was induced by subjecting BV-2 microglia to 200 μM hydrogen peroxide (H2O2) for 24 h. MTT assay was used to determine cell viability. Changes of intracellular reactive oxygen species (ROS) and apoptosis were analyzed by flow cytometry. Three episcleral veins were cauterized to induce high IOP in Wistar rats and measured by Tonopen. After 6 weeks of treatment with curcumin (10 mg/kg/day) by intragastric administration, surviving of retinal ganglion cells was quantified. Activation of caspase 3, cytochrome c, BAX, and BCL2 was quantified by Western blotting both in BV-2 microglia and in animal model. Data were analyzed with the GraphPad Prism 5.0 software, and Pcurcumin, the cell viability increased and the intracellular ROS and apoptosis significantly decreased. In the in vivo study, chronic mild IOP elevation was induced for 4 weeks. In the curcumin-treated group, curcumin protected rat BV-2 microglia from death significantly. In both H2O2-treated BV-2 microglia and glaucoma models, caspase 3, cytochrome c, and BAX were downregulated and BCL2 was upregulated in the curcumin-treated group. Curcumin affords neuroprotective effects by inhibiting oxidative damage and could be a new or adjunctive treatment for glaucoma.

  7. The neuropathological basis to the functional role of microglia/macrophages in gliomas.

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    Schiffer, Davide; Mellai, Marta; Bovio, Enrica; Annovazzi, Laura

    2017-09-01

    The paper wants to be a tracking shot of the main recent acquisitions on the function and significance of microglia/macrophages in gliomas. The observations have been principally carried out on in vitro cultures and on tumor transplants in animals. Contrary to what is deduced from microglia in non-neoplastic pathologic conditions of central nervous system (CNS), most conclusions indicate that microglia acts favoring tumor proliferation through an immunosuppression induced by glioma cells. By immunohistochemistry, different microglia phenotypes are recognized in gliomas, from ramified microglia to frank macrophagic aspect. One wonders whether the functional conclusions drawn from many microglia studies, but not in conditions of human pathology, apply to all the phenotypes recognizable in them. It is difficult to verify in human pathology a prognostic significance of microglia. Only CD163-positive microglia/macrophages inversely correlate with glioma patients' survival, whereas the total number of microglia does not change with the malignancy grade.

  8. Polyphenols, Antioxidants and the Sympathetic Nervous System.

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    Bruno, Rosa Maria; Ghiadoni, Lorenzo

    2018-01-01

    A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity, metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympathoexcitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel therapeutic

  9. What is microglia neurotoxicity (Not)?

    DEFF Research Database (Denmark)

    Biber, Knut; Owens, Trevor; Boddeke, Erik

    2014-01-01

    and vulnerable organ like the brain should host numerous potential killers, we here review the concept of microglia neurotoxicity. On one hand it is discussed that most of our understanding about how microglia kill neurons is based on in vitro experiments or correlative staining studies that suffer from...... the difficulty to discriminate microglia and peripheral myeloid cells in the diseased brain. On the other hand it is described that a more functional approach by mutating, inactivating or deleting microglia is seldom associated with a beneficial outcome in an acute injury situation, suggesting that microglia...

  10. Inflammation leads to distinct populations of extracellular vesicles from microglia

    DEFF Research Database (Denmark)

    Yang, Yiyi; Boza-Serrano, Antonio; Dunning, Christopher J.R.

    2018-01-01

    Background: Activated microglia play an essential role in inflammatory responses elicited in the central nervous system (CNS). Microglia-derived extracellular vesicles (EVs) are suggested to be involved in propagation of inflammatory signals and in the modulation of cell-to-cell communication...

  11. MafB antagonizes phenotypic alteration induced by GM-CSF in microglia

    Energy Technology Data Exchange (ETDEWEB)

    Koshida, Ryusuke, E-mail: rkoshida-myz@umin.ac.jp; Oishi, Hisashi, E-mail: hoishi@md.tsukuba.ac.jp; Hamada, Michito; Takahashi, Satoru

    2015-07-17

    Microglia are tissue-resident macrophages which are distributed throughout the central nervous system (CNS). Recent studies suggest that microglia are a unique myeloid population distinct from peripheral macrophages in terms of origin and gene expression signature. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic cytokine regulating myeloid development, has been shown to stimulate proliferation and alter phenotype of microglia in vitro. However, how its signaling is modulated in microglia is poorly characterized. MafB, a bZip transcriptional factor, is highly expressed in monocyte-macrophage lineage cells including microglia, although its role in microglia is largely unknown. We investigated the crosstalk between GM-CSF signaling and MafB by analyzing primary microglia. We found that Mafb-deficient microglia grew more rapidly than wild-type microglia in response to GM-CSF. Moreover, the expression of genes associated with microglial differentiation was more downregulated in Mafb-deficient microglia cultured with GM-CSF. Notably, such differences between the genotypes were not observed in the presence of M-CSF. In addition, we found that Mafb-deficient microglia cultured with GM-CSF barely extended their membrane protrusions, probably due to abnormal activation of RhoA, a key regulator of cytoskeletal remodeling. Altogether, our study reveals that MafB is a negative regulator of GM-CSF signaling in microglia. These findings could provide new insight into the modulation of cytokine signaling by transcription factors in microglia. - Highlights: • GM-CSF alters the phenotype of microglia in vitro more potently than M-CSF. • Transcription factor MafB antagonizes the effect of GM-CSF on microglia in vitro. • MafB deficiency leads to RhoA activation in microglia in response to GM-CSF. • We show for the first time the function of MafB in microglia.

  12. Histamine Regulates the Inflammatory Profile of SOD1-G93A Microglia and the Histaminergic System Is Dysregulated in Amyotrophic Lateral Sclerosis

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    Savina Apolloni

    2017-11-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a late-onset motor neuron disease where activated glia release pro-inflammatory cytokines that trigger a vicious cycle of neurodegeneration in the absence of resolution of inflammation. Given the well-established role of histamine as a neuron-to-glia alarm signal implicated in brain disorders, the aim of this study was to investigate the expression and regulation of the histaminergic pathway in microglial activation in ALS mouse model and in humans. By examining the contribution of the histaminergic system to ALS, we found that particularly via H1 and H4 receptors, histamine promoted an anti-inflammatory profile in microglia from SOD1-G93A mice by modulating their activation state. A decrease in NF-κB and NADPH oxidase 2 with an increase in arginase 1 and P2Y12 receptor was induced by histamine only in the ALS inflammatory environment, but not in the healthy microglia, together with an increase in IL-6, IL-10, CD163, and CD206 phenotypic markers in SOD1-G93A cells. Moreover, histaminergic H1, H2, H3, and H4 receptors, and histamine metabolizing enzymes histidine decarboxylase, histamine N-methyltransferase, and diamine oxidase were found deregulated in spinal cord, cortex, and hypothalamus of SOD1-G93A mice during disease progression. Finally, by performing a meta-analysis study, we found a modulated expression of histamine-related genes in cortex and spinal cord from sporadic ALS patients. Our findings disclose that histamine acts as anti-inflammatory agent in ALS microglia and suggest a dysregulation of the histaminergic signaling in ALS.

  13. Nutritional and nanotechnological modulators of microglia

    Directory of Open Access Journals (Sweden)

    Dusica Maysinger

    2016-07-01

    Full Text Available Microglia are the essential responders to alimentary, pharmacological and nanotechnological immunomodulators. These neural cells play multiple roles as surveyors, sculptors, and guardians of essential parts of complex neural circuitries. Microglia can play dual roles in the central nervous system; they can be deleterious and/or protective. The immunomodulatory effects of alimentary components, gut microbiota and nanotechnological products have been investigated in microglia at the single cell level and in vivo using intravital imaging approaches, and different biochemical assays. This review highlights some of the emerging questions and topics from studies involving alimentation, microbiota, nanotechnological products, and associated problems in this area of research. Some of the advantages and limitations of in vitro and in vivo models used to study the neuromodulatory effects of these factors, as well as the merits and pitfalls of intravital imaging modalities employed are presented.

  14. Antioxidants

    Science.gov (United States)

    Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods, including fruits and ... are also available as dietary supplements. Examples of antioxidants include Beta-carotene Lutein Lycopene Selenium Vitamin A ...

  15. Studies on the hepatic antioxidant defense system in &lambda ...

    African Journals Online (AJOL)

    Studies on the hepatic antioxidant defense system in λ cyhalothrin-induced ... Significant (P<0.05) elevation in the level of lipid peroxidation was observed in λ ... The results of the present investigation have indicated that the tissue antioxidant defense system is operating at a lower rate despite ... HOW TO USE AJOL.

  16. Pyrroloquinoline quinone (PQQ inhibits lipopolysaccharide induced inflammation in part via downregulated NF-κB and p38/JNK activation in microglial and attenuates microglia activation in lipopolysaccharide treatment mice.

    Directory of Open Access Journals (Sweden)

    Chongfei Yang

    Full Text Available Therapeutic strategies designed to inhibit the activation of microglia may lead to significant advancement in the treatment of most neurodegenerative diseases. Pyrroloquinoline quinone (PQQ is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and has been reported to exert potent immunosuppressive effects. In the present study, the anti-inflammatory effects of PQQ was investigated in LPS treated primary microglia cells. Our observations showed that pretreatment with PQQ significantly inhibited the production of NO and PGE2 and suppressed the expression of pro-inflammatory mediators such as iNOS, COX-2, TNF-a, IL-1b, IL-6, MCP-1 and MIP-1a in LPS treated primary microglia cells. The nuclear translocation of NF-κB and the phosphorylation level of p65, p38 and JNK MAP kinase pathways were also inhibited by PQQ in LPS stimulated primary microglia cells. Further a systemic LPS treatment acute inflammation murine brain model was used to study the suppressive effects of PQQ against neuroinflammation in vivo. Mice treated with PQQ demonstrated marked attenuation of neuroinflammation based on Western blotting and immunohistochemistry analysis of Iba1-against antibody in the brain tissue. Indicated that PQQ protected primary cortical neurons against microglia-mediated neurotoxicity. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of neurodegenerative diseases associated with microglia activation.

  17. Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Monica R P Elmore

    Full Text Available Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored. Here, we examine the responsiveness of newly repopulated microglia to an inflammatory stimulus, as well as determine the impact of these cells on behavior, cognition, and neuroinflammation. Two month-old wild-type mice were placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397 diet was then removed in a subset of animals to allow microglia to repopulate and behavioral testing conducted beginning at 14 d repopulation. Finally, inflammatory profiling of the microglia-repopulated brain in response to lipopolysaccharide (LPS; 0.25 mg/kg or phosphate buffered saline (PBS was determined 21 d after inhibitor removal using quantitative real time polymerase chain reaction (RT-PCR, as well as detailed analyses of microglial morphologies. We find mice with repopulated microglia to perform similarly to controls by measures of behavior, cognition, and motor function. Compared to control/resident microglia, repopulated microglia had larger cell bodies and less complex branching in their processes, which resolved over time after inhibitor removal. Inflammatory profiling revealed that the mRNA gene expression of repopulated microglia was similar to normal resident microglia and that these new cells appear functional and responsive to LPS. Overall, these data demonstrate that newly repopulated microglia function

  18. JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

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    Ling Yan

    2013-01-01

    Full Text Available Excessive fluoride may cause central nervous system (CNS dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS, and NADPH oxidase (NOX is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells.

  19. JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

    Science.gov (United States)

    Yan, Ling; Liu, Shengnan; Wang, Chen; Wang, Fei; Song, Yingli; Yan, Nan; Xi, Shuhua; Liu, Ziyou; Sun, Guifan

    2013-01-01

    Excessive fluoride may cause central nervous system (CNS) dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS), and NADPH oxidase (NOX) is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular O2 ·− and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL) resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells. PMID:24072958

  20. The Lifespan and Turnover of Microglia in the Human Brain

    Directory of Open Access Journals (Sweden)

    Pedro Réu

    2017-07-01

    Full Text Available The hematopoietic system seeds the CNS with microglial progenitor cells during the fetal period, but the subsequent cell generation dynamics and maintenance of this population have been poorly understood. We report that microglia, unlike most other hematopoietic lineages, renew slowly at a median rate of 28% per year, and some microglia last for more than two decades. Furthermore, we find no evidence for the existence of a substantial population of quiescent long-lived cells, meaning that the microglia population in the human brain is sustained by continuous slow turnover throughout adult life.

  1. Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia

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    Philip W. Brownjohn

    2018-04-01

    Full Text Available Summary: The derivation of microglia from human stem cells provides systems for understanding microglial biology and enables functional studies of disease-causing mutations. We describe a robust method for the derivation of human microglia from stem cells, which are phenotypically and functionally comparable with primary microglia. We used stem cell-derived microglia to study the consequences of missense mutations in the microglial-expressed protein triggering receptor expressed on myeloid cells 2 (TREM2, which are causal for frontotemporal dementia-like syndrome and Nasu-Hakola disease. We find that mutant TREM2 accumulates in its immature form, does not undergo typical proteolysis, and is not trafficked to the plasma membrane. However, in the absence of plasma membrane TREM2, microglia differentiate normally, respond to stimulation with lipopolysaccharide, and are phagocytically competent. These data indicate that dementia-associated TREM2 mutations have subtle effects on microglia biology, consistent with the adult onset of disease in individuals with these mutations. : Brownjohn and colleagues report methods to generate microglia from induced pluripotent human stem cells, which they demonstrate are highly similar to cultured primary human microglia. Microglia differentiated from patient-derived stem cells carrying neurological disease-causing mutations in the TREM2 receptor differentiate normally and respond appropriately to pathogenic stimuli, despite the absence of functional TREM2 receptor on the plasma membrane. Keywords: dementia, microglia, TREM2, Nasu-Hakola disease, frontotemporal dementia, iPSC-microglia, neuroinflammation

  2. Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue.

    Science.gov (United States)

    Tamashiro, Tami T; Dalgard, Clifton Lee; Byrnes, Kimberly R

    2012-08-15

    Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain injury, and nervous system infection. Under these activating conditions, microglia increase their phagocytic activity, undergo morpohological and proliferative change, and actively secrete reactive oxygen and nitrogen species, pro-inflammatory chemokines and cytokines, often activating a paracrine or autocrine loop. As these microglial responses contribute to disease pathogenesis in neurological conditions, research focused on microglia is warranted. Due to the cellular heterogeneity of the brain, it is technically difficult to obtain sufficient microglial sample material with high purity during in vivo experiments. Current research on the neuroprotective and neurotoxic functions of microglia require a routine technical method to consistently generate pure and healthy microglia with sufficient yield for study. We present, in text and video, a protocol to isolate pure primary microglia from mixed glia cultures for a variety of downstream applications. Briefly, this technique utilizes dissociated brain tissue from neonatal rat pups to produce mixed glial cell cultures. After the mixed glial cultures reach confluency, primary microglia are mechanically isolated from the culture by a brief duration of shaking. The microglia are then plated at high purity for experimental study. The principle and protocol of this methodology have been described in the literature. Additionally, alternate methodologies to isolate primary microglia are well described. Homogenized brain tissue may be separated

  3. Developmental stage of oligodendrocytes determines their response to activated microglia in vitro

    Directory of Open Access Journals (Sweden)

    Bresnahan Jacqueline C

    2007-11-01

    Full Text Available Abstract Background Oligodendrocyte progenitor cells (OPCs and mature oligodendrocytes are both lost in central nervous system injury and disease. Activated microglia may play a role in OPC and oligodendrocyte loss or replacement, but it is not clear how the responses of OPCs and oligodendrocytes to activated microglia differ. Methods OPCs and microglia were isolated from rat cortex. OPCs were induced to differentiate into oligodendrocytes with thyroid hormone in defined medium. For selected experiments, microglia were added to OPC or oligodendrocyte cultures. Lipopolysaccharide was used to activate microglia and microglial activation was confirmed by TNFα ELISA. Cell survival was assessed with immunocytochemistry and cell counts. OPC proliferation and oligodendrocyte apoptosis were also assessed. Results OPCs and oligodendrocytes displayed phenotypes representative of immature and mature oligodendrocytes, respectively. Activated microglia reduced OPC survival, but increased survival and reduced apoptosis of mature oligodendrocytes. Activated microglia also underwent cell death themselves. Conclusion Activated microglia may have divergent effects on OPCs and mature oligodendrocytes, reducing OPC survival and increasing mature oligodendrocyte survival. This may be of importance because activated microglia are present in several disease states where both OPCs and mature oligodendrocytes are also reacting to injury. Activated microglia may simultaneously have deleterious and helpful effects on different cells after central nervous system injury.

  4. A systems biology perspective on Nrf2-mediated antioxidant response

    International Nuclear Information System (INIS)

    Zhang Qiang; Pi Jingbo; Woods, Courtney G.; Andersen, Melvin E.

    2010-01-01

    Cells in vivo are constantly exposed to reactive oxygen species (ROS) generated endogenously and exogenously. To defend against the deleterious consequences of ROS, cells contain multiple antioxidant enzymes expressed in various cellular compartments to scavenge these toxic species. Under oxidative stresses, these antioxidant enzymes are upregulated to restore redox homeostasis. Such an adaptive response results from the activation of a redox-sensitive gene regulatory network mediated by nuclear factor E2-related factor 2. To more completely understand how the redox control system is designed by nature to meet homeostatic goals, we have examined the network from a systems perspective using engineering approaches. As with man-made control devices, the redox control system can be decomposed into distinct functional modules, including transducer, controller, actuator, and plant. Cells achieve specific performance objectives by utilizing nested feedback loops, feedforward control, and ultrasensitive signaling motifs, etc. Given that endogenously generated ROS are also used as signaling molecules, our analysis suggests a novel mode of action to explain oxidative stress-induced pathological conditions and diseases. Specifically, by adaptively upregulating antioxidant enzymes, oxidative stress may inadvertently attenuate ROS signals that mediate physiological processes, resulting in aberrations of cellular functions and adverse consequences. Lastly, by simultaneously considering the two competing cellular tasks-adaptive antioxidant defense and ROS signaling-we re-examine the premise that dietary antioxidant supplements is generally beneficial to human health. Our analysis highlights some possible adverse effects of these widely consumed antioxidants.

  5. Microglia Responses in Acute and Chronic Neurological Diseases: What Microglia-Specific Transcriptomic Studies Taught (and did Not Teach Us

    Directory of Open Access Journals (Sweden)

    Hélène E. Hirbec

    2017-07-01

    Full Text Available Over the last decade, microglia have been acknowledged to be key players in central nervous system (CNS under both physiological and pathological conditions. They constantly survey the CNS environment and as immune cells, in pathological contexts, they provide the first host defense and orchestrate the immune response. It is well recognized that under pathological conditions microglia have both sequential and simultaneous, beneficial and detrimental effects. Cell-specific transcriptomics recently became popular in Neuroscience field allowing concurrent monitoring of the expression of numerous genes in a given cell population. Moreover, by comparing two or more conditions, these approaches permit to unbiasedly identify deregulated genes and pathways. A growing number of studies have thus investigated microglial transcriptome remodeling over the course of neuropathological conditions and highlighted the molecular diversity of microglial response to different diseases. In the present work, we restrict our review to microglia obtained directly from in vivo samples and not cell culture, and to studies using whole-genome strategies. We first critically review the different methods developed to decipher microglia transcriptome. In particular, we compare advantages and drawbacks of flow cytometry and laser microdissection to isolate pure microglia population as well as identification of deregulated microglial genes obtained via RNA sequencing (RNA-Seq vs. microarrays approaches. Second, we summarize insights obtained from microglia transcriptomes in traumatic brain and spinal cord injuries, pain and more chronic neurological conditions including Amyotrophic lateral sclerosis (ALS, Alzheimer disease (AD and Multiple sclerosis (MS. Transcriptomic responses of microglia in other non-neurodegenerative CNS disorders such as gliomas and sepsis are also addressed. Third, we present a comparison of the most activated pathways in each neuropathological condition

  6. Recent Advances in the Study of Bipolar/Rod-Shaped Microglia and their Roles in Neurodegeneration

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    Ngan Pan Bennett Au

    2017-05-01

    Full Text Available Microglia are the resident immune cells of the central nervous system (CNS and they contribute to primary inflammatory responses following CNS injuries. The morphology of microglia is closely associated with their functional activities. Most previous research efforts have attempted to delineate the role of ramified and amoeboid microglia in the pathogenesis of neurodegenerative diseases. In addition to ramified and amoeboid microglia, bipolar/rod-shaped microglia were first described by Franz Nissl in 1899 and their presence in the brain was closely associated with the pathology of infectious diseases and sleeping disorders. However, studies relating to bipolar/rod-shaped microglia are very limited, largely due to the lack of appropriate in vitro and in vivo experimental models. Recent studies have reported the formation of bipolar/rod-shaped microglia trains in in vivo models of CNS injury, including diffuse brain injury, focal transient ischemia, optic nerve transection and laser-induced ocular hypertension (OHT. These bipolar/rod-shaped microglia formed end-to-end alignments in close proximity to the adjacent injured axons, but they showed no interactions with blood vessels or other types of glial cell. Recent studies have also reported on a highly reproducible in vitro culture model system to enrich bipolar/rod-shaped microglia that acts as a powerful tool with which to characterize this form of microglia. The molecular aspects of bipolar/rod-shaped microglia are of great interest in the field of CNS repair. This review article focuses on studies relating to the morphology and transformation of microglia into the bipolar/rod-shaped form, along with the differential gene expression and spatial distribution of bipolar/rod-shaped microglia in normal and pathological CNSs. The spatial arrangement of bipolar/rod-shaped microglia is crucial in the reorganization and remodeling of neuronal and synaptic circuitry following CNS injuries. Finally, we

  7. Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood.

    Science.gov (United States)

    Schaafsma, Wandert; Basterra, Laura Bozal; Jacobs, Sabrina; Brouwer, Nieske; Meerlo, Peter; Schaafsma, Anne; Boddeke, Erik W G M; Eggen, Bart J L

    2017-10-01

    Maternal inflammation during pregnancy can have detrimental effects on embryonic development that persist during adulthood. However, the underlying mechanisms and insights in the responsible cell types are still largely unknown. Here we report the effect of maternal inflammation on fetal microglia, the innate immune cells of the central nervous system (CNS). In mice, a challenge with LPS during late gestation stages (days 15-16-17) induced a pro-inflammatory response in fetal microglia. Adult whole brain microglia of mice that were exposed to LPS during embryonic development displayed a persistent reduction in pro-inflammatory activation in response to a re-challenge with LPS. In contrast, hippocampal microglia of these mice displayed an increased inflammatory response to an LPS re-challenge. In addition, a reduced expression of brain-derived neurotrophic factor (BDNF) was observed in hippocampal microglia of LPS-offspring. Microglia-derived BDNF has been shown to be important for learning and memory processes. In line with these observations, behavioral- and learning tasks with mice that were exposed to maternal inflammation revealed reduced home cage activity, reduced anxiety and reduced learning performance in a T-maze. These data show that exposure to maternal inflammation during late gestation results in long term changes in microglia responsiveness during adulthood, which is different in nature in hippocampus compared to total brain microglia. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Huperzine A protects neural stem cells against Aβ-induced apoptosis in a neural stem cells and microglia co-culture system

    Science.gov (United States)

    Zhu, Ning; Lin, Jizong; Wang, Kewan; Wei, Meidan; Chen, Qingzhuang; Wang, Yong

    2015-01-01

    Objectives: This study aims to explore whether Huperzine A (HupA) could protect neural stem cells against amyloid beta-peptide Aβ induced apoptosis in a neural stem cells (NSCs) and microglia co-culture system. Methods: Rat NSCs and microglial cells were isolated, cultured and identified with immunofluorescence Assays (IFA). Co-culture systems of NSCs and microglial cells were employed using Transwell Permeable Supports. The effects of Aβ1-42 on NSCs were studied in 4 groups using co-culture systems: NSCs, Aβ+NSCs, co-culture and Aβ+co-culture groups. Bromodeoxyuridine (BrdU) incorporation and flow cytometry were utilized to assess the differences of proliferation, differentiation and apoptosis of NSCs between the groups. LQ test was performed to assess the amounts of IL-6, TNF-α and MIP-α secreted, and flow cytometry and Western blotting were used to assess apoptosis of NSCs and the expressions of Bcl-2 and Bax in each group. Results: IFA results showed that isolated rat NSCs were nestin-positive and microglial cells were CD11b/c-positive. Among all the groups, the Aβ+co-culture group has the lowest BrdU expression level, the lowest MAP2-positive, ChAT-positive cell counts and the highest NSC apoptosis rate. Smaller amounts of IL-6, TNF-α and MIP-α were being secreted by microglial cells in the HupA+Aβ+co-culture group compared with those in the Aβ+ co-culture group. Also the Bcl-2: Bax ratio was much higher in the HupA+Aβ+co-culture group than in the Aβ+co-culture group. Conclusions: HupA inhibits cell apoptosis through restraining microglia’s inflammatory response induced by Aβ1-42. PMID:26261518

  9. Antioxidant status, immune system, blood metabolites and carcass ...

    African Journals Online (AJOL)

    This experiment was conducted to evaluate the effects of dietary turmeric rhizome powder (TP) on performance, blood metabolite, immune system, antioxidant status, and relative weight of organs in pre and post heat stressed broilers. Two hundred and sixty-four (264) day-old male Arian broiler chicks were randomly ...

  10. Liposomal clodronate selectively eliminates microglia from primary astrocyte cultures

    Directory of Open Access Journals (Sweden)

    Kumamaru Hiromi

    2012-05-01

    Full Text Available Abstract Background There is increasing interest in astrocyte biology because astrocytes have been demonstrated to play prominent roles in physiological and pathological conditions of the central nervous system, including neuroinflammation. To understand astrocyte biology, primary astrocyte cultures are most commonly used because of the direct accessibility of astrocytes in this system. However, this advantage can be hindered by microglial contamination. Although several authors have warned regarding microglial contamination in this system, complete microglial elimination has never been achieved. Methods The number and proliferative potential of contaminating microglia in primary astrocyte cultures were quantitatively assessed by immunocytologic and flow cytometric analyses. To examine the utility of clodronate for microglial elimination, primary astrocyte cultures or MG-5 cells were exposed to liposomal or free clodronate, and then immunocytologic, flow cytometric, and gene expression analyses were performed. The gene expression profiles of microglia-eliminated and microglia-contaminated cultures were compared after interleukin-6 (IL-6 stimulation. Results The percentage of contaminating microglia exceeded 15% and continued to increase because of their high proliferative activity in conventional primary astrocyte cultures. These contaminating microglia were selectively eliminated low concentration of liposomal clodronate. Although primary microglia and MG-5 cells were killed by both liposomal and free clodronate, free clodronate significantly affected the viability of astrocytes. In contrast, liposomal clodronate selectively eliminated microglia without affecting the viability, proliferation or activation of astrocytes. The efficacy of liposomal clodronate was much higher than that of previously reported methods used for decreasing microglial contamination. Furthermore, we observed rapid tumor necrosis factor-α and IL-1b gene induction in

  11. Bidirectional Microglia-Neuron Communication in the Healthy Brain

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    Ukpong B. Eyo

    2013-01-01

    Full Text Available Unlike other resident neural cells that are of neuroectodermal origin, microglia are resident neural cells of mesodermal origin. Traditionally recognized for their immune functions during disease, new roles are being attributed to these cells in the development and maintenance of the central nervous system (CNS including specific communication with neurons. In this review, we highlight some of the recent findings on the bidirectional interaction between neurons and microglia. We discuss these interactions along two lines. First, we review data that suggest that microglial activity is modulated by neuronal signals, focusing on evidence that (i neurons are capable of regulating microglial activation state and influence basal microglial activities; (ii classic neurotransmitters affect microglial behavior; (iii chemotactic signals attract microglia during acute neuronal injury. Next, we discuss some of the recent data on how microglia signal to neurons. Signaling mechanisms include (i direct physical contact of microglial processes with neuronal elements; (ii microglial regulation of neuronal synapse and circuit by fractalkine, complement, and DAP12 signaling. In addition, we discuss the use of microglial depletion strategies in studying the role of microglia in neuronal development and synaptic physiology. Deciphering the mechanisms of bidirectional microglial-neuronal communication provides novel insights in understanding microglial function in both the healthy and diseased brain.

  12. Microglia in Alzheimer's Disease: It's All About Context

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    Tara M. Weitz

    2012-01-01

    Full Text Available Neuroinflammation is now regarded as both an early event and prime mover in the pathobiology of Alzheimer disease (AD, a neurodegenerative disease that represents a growing public health threat. As the resident innate immune cells within the central nervous system, microglia are centrally positioned as key orchestrators of brain inflammation. It is now accepted that numerous forms of activated microglia exist. Furthermore, while some types of reactive microglia are detrimental, others can actually be beneficial. In the context of AD etiopathology, much debate surrounds whether these enigmatic cells play “good” or “bad” roles. In this article, we distill a complex clinical and experimental literature focused on the contribution of microglia to AD pathology and progression. A synthesis of the literature only seems possible when considering context– the conditions under which microglia encounter and mount immunological responses to AD pathology. In order to carry out these diverse contextual responses, a number of key receptors and signaling pathways are variously activated. It will be critically important for future studies to address molecular mediators that lead to beneficial microglial responses and therefore represent important therapeutic targets for AD.

  13. A starring role for microglia in brain sex differences.

    Science.gov (United States)

    Lenz, Kathryn M; McCarthy, Margaret M

    2015-06-01

    Microglia, the resident innate immune cells in the brain, have long been understood to be crucial to maintenance in the nervous system, by clearing debris, monitoring for infiltration of infectious agents, and mediating the brain's inflammatory and repair response to traumatic injury, stroke, or neurodegeneration. A wave of new research has shown that microglia are also active players in many basic processes in the healthy brain, including cell proliferation, synaptic connectivity, and physiology. Microglia, both in their capacity as phagocytic cells and via secretion of many neuroactive molecules, including cytokines and growth factors, play a central role in early brain development, including sexual differentiation of the brain. In this review, we present the vast roles microglia play in normal brain development and how perturbations in the normal neuroimmune environment during development may contribute to the etiology of brain-based disorders. There are notable differences between microglia and neuroimmune signaling in the male and female brain throughout the life span, and these differences may contribute to the vast differences in the incidence of neuropsychiatric and neurological disorders between males and females. © The Author(s) 2014.

  14. Effects of Artea, a systemic fungicide, on the antioxidant system and ...

    African Journals Online (AJOL)

    Effects of Artea, a systemic fungicide, on the antioxidant system and the respiratory activity of durum wheat ( Triticum durum L .). ... African Journal of Biotechnology ... Root respiratory activity was also determined using a polarographic method ...

  15. Modulation of Hematopoietic Lineage Specification Impacts TREM2 Expression in Microglia-Like Cells Derived From Human Stem Cells.

    Science.gov (United States)

    Amos, Peter J; Fung, Susan; Case, Amanda; Kifelew, Jerusalem; Osnis, Leah; Smith, Carole L; Green, Kevin; Naydenov, Alipi; Aloi, Macarena; Hubbard, Jesse J; Ramakrishnan, Aravind; Garden, Gwenn A; Jayadev, Suman

    2017-01-01

    Microglia are the primary innate immune cell type in the brain, and their dysfunction has been linked to a variety of central nervous system disorders. Human microglia are extraordinarily difficult to obtain for experimental investigation, limiting our ability to study the impact of human genetic variants on microglia functions. Previous studies have reported that microglia-like cells can be derived from human monocytes or pluripotent stem cells. Here, we describe a reproducible relatively simple method for generating microglia-like cells by first deriving embryoid body mesoderm followed by exposure to microglia relevant cytokines. Our approach is based on recent studies demonstrating that microglia originate from primitive yolk sac mesoderm distinct from peripheral macrophages that arise during definitive hematopoiesis. We hypothesized that functional microglia could be derived from human stem cells by employing BMP-4 mesodermal specification followed by exposure to microglia-relevant cytokines, M-CSF, GM-CSF, IL-34, and TGF-β. Using immunofluorescence microscopy, flow cytometry, and reverse transcription polymerase chain reaction, we observed cells with microglia morphology expressing a repertoire of markers associated with microglia: Iba1, CX3CR1, CD11b, TREM2, HexB, and P2RY12. These microglia-like cells maintain myeloid functional phenotypes including Aβ peptide phagocytosis and induction of pro-inflammatory gene expression in response to lipopolysaccharide stimulation. Addition of small molecules BIO and SB431542, previously demonstrated to drive definitive hematopoiesis, resulted in decreased surface expression of TREM2. Together, these data suggest that mesodermal lineage specification followed by cytokine exposure produces microglia-like cells in vitro from human pluripotent stem cells and that this phenotype can be modulated by factors influencing hematopoietic lineage in vitro.

  16. The antioxidative system of Norway spruce: Effects of different stress factors. Das antioxidative System der Fichte: Einfluss von verschiedenen Stressfaktoren

    Energy Technology Data Exchange (ETDEWEB)

    Schittenhelm, J. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany)); Westphal, S. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany)); Toder, S. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany)); Wagner, E. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany))

    1993-08-01

    The effects of different stress factors on the antioxidative system of 6-year-old Norway spruces of the same clone were examined. Flooding and permanent darkness had only minor effects. On the other hand drought, chilling, intense light, and very high ozone concentrations showed strong but distinct consequences. This indicates that the damages by these stress factors are due to different toxic oxygen species, and that the stress factors could produce synergistic damages under natural field conditions. (orig.)

  17. High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia.

    Science.gov (United States)

    Baufeld, Caroline; Osterloh, Anja; Prokop, Stefan; Miller, Kelly R; Heppner, Frank L

    2016-09-01

    Diets high in fat (HFD) are known to cause an immune response in the periphery as well as the central nervous system. In peripheral adipose tissue, this immune response is primarily mediated by macrophages that are recruited to the tissue. Similarly, reactivity of microglia, the innate immune cells of the brain, has been shown to occur in the hypothalamus of mice fed a high-fat diet. To characterize the nature of the microglial response to diets high in fat in a temporal fashion, we studied the phenotypic spectrum of hypothalamic microglia of mice fed high-fat diet for 3 days and 8 weeks by assessing their tissue reaction and inflammatory signature. While we observed a significant increase in Iba1+ myeloid cells and a reaction of GFAP+ astrocytes in the hypothalamus after 8 weeks of HFD feeding, we found the hypothalamic myeloid cell reaction to be limited to endogenous microglia and not mediated by infiltrating myeloid cells. Moreover, obese humans were found to present with signs of hypothalamic gliosis and exacerbated microglia dystrophy, suggesting a targeted microglia response to diet in humans as well. Notably, the glial reaction occurring in the mouse hypothalamus was not accompanied by an increase in pro-inflammatory cytokines, but rather by an anti-inflammatory reaction. Gene expression analyses of isolated microglia not only confirmed this observation, but also revealed a downregulation of microglia genes important for sensing signals in the microenvironment. Finally, we demonstrate that long-term exposure of microglia to HFD in vivo does not impair the cell's ability to respond to additional stimuli, like lipopolysaccharide. Taken together, our findings support the notion that microglia react to diets high in fat in a region-specific manner in rodents as well as in humans; however, this response changes over time as it is not exclusively pro-inflammatory nor does exposure to HFD prime microglia in the hypothalamus.

  18. Lipophilized phenolics as antioxidants in fish oil enriched food systems

    DEFF Research Database (Denmark)

    Sørensen, Ann-Dorit Moltke; Nielsen, Nina Skall; Jacobsen, Charlotte

    Food products containing long chain omega-3 PUFA are highly susceptible to oxidation, which causes undesirable flavors and loss of health beneficial fatty acids. Many omega-3 enriched food products on the market are oil-in-water emulsions. According to the so called “polar paradox”, polar compounds...... hypothesis is that lipophilization of such polar phenolic compounds may improve their efficacy in fish oil enriched food systems. Our study aimed at evaluating rutin and dihydrocaffeic acid and their esters as antioxidants in o/w emulsion model system and milk enriched with fish oil. Moreover, the effect...

  19. Sortilin in microglia reactivity

    DEFF Research Database (Denmark)

    Svenningsen, Anne Louise Søby; Jager, Sara Buskbjerg; Richner, Mette

    Neuropathic pain is a serious neurological disease estimated to affect around 8% of the Western population. It can be caused by either direct injuries to the peripheral nervous system (e.g. surgery) or indirect injuries (e.g. diabetes or cancer). Unfortunately, patients very often do not respond ...

  20. Antioxidant Activity of Flaxseed Extracts in Lipid Systems

    Directory of Open Access Journals (Sweden)

    Adriana Slavova-Kazakova

    2015-12-01

    Full Text Available The aim of this work was to compare the antioxidant activity of the extract of flaxseed and its alkaline hydrolysate in two model systems: lipid autoxidation of triacylglycerols of sunflower oil (TGSO—in a homogeneous lipid media and during β-carotene-linoleate emulsion system. In addition, pure lignans were tested. The material was defatted with hexane and then phenolic compounds were extracted using dioxane-ethanol (50:50, v/v mixture. Carbohydrates were removed from the crude extract using an Amberlite XAD-16 column chromatography. The content of total phenolic compounds in the crude extract and after alkaline hydrolysis was determined using a Folin-Ciocalteu’s phenol reagent. Individual phenolic compounds were determined by nordihydroguaiaretic acid (RP-HPLC method in gradient system. The alkaline hydrolysis increased the content of total phenolics in the extract approximately by 10%. In the extracts of flaxseed, phenolic compounds were present in the form of macromolecular complex. In the alkaline hydrolysate, secoisolariciresinol diglucoside (SDG was found as the main phenolic compound. Small amounts of p-coumaric and ferulic acids were also determined. SDG and both extracts were not able to inhibit effectively lipid autoxidation. The kinetics of TGSO autoxidation at 80 °C in absence and in presence of the extract before hydrolysis (EBH and after hydrolysis (EAH was monitored and compared with known standard antioxidants. Ferulic acid (FA and butylated hydroxyl toluene (BHT showed much higher antioxidant efficiency and reactivity than that of both extracts. Secoisolariciresinol (SECO showed a higher activity in both model systems than SDG. However, the activity of SECO was much lower than that of nordihydroquaiaretic acid (NDGA.

  1. Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia

    Directory of Open Access Journals (Sweden)

    Stephanie A. Amici

    2017-11-01

    Full Text Available Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals via molecular programs to define pathogen/injury inflammatory responses provides an opportunity to better understand the multilayered nature of macrophages, as well as target and modulate cellular programs to control excessive inflammation. This is particularly important in MS and other neuroinflammatory diseases, where chronic inflammatory macrophage and microglial responses may contribute to pathology. Here, we perform a comprehensive review of our current understanding of how molecular pathways modulate tissue macrophage phenotype, covering both classic pathways and the emerging role of microRNAs, receptor-tyrosine kinases and metabolism in macrophage phenotype. In addition, we discuss pathway parallels in microglia, novel markers helpful in the identification of peripheral macrophages versus microglia and markers linked to their phenotype.

  2. Microglia energy metabolism in metabolic disorder

    NARCIS (Netherlands)

    Kalsbeek, Martin J. T.; Mulder, Laurie; Yi, Chun-Xia

    2016-01-01

    Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This

  3. Ginsan activated the antioxidant defense systems in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jie Young; Son, Soo Jung; Ahn, Ji Yeon; Shim, Ji Young; Han, Young Soo; Jung, In Sung; Yun, Yeon Sook [KIRMS Daegu (Korea, Republic of)

    2003-07-01

    Ginsan, a polysaccharide extracted from Panax ginseng, has hematopoietic activity and is also known as a good biological-response modifier. In this investigation, we studied the effects of ginsan on the {gamma}-radiation induced alterations of some antioxidant systems in spleen of Balb/c mice. There are many data that irradiation induces Reactive Oxygen Species (ROS), which plays an important causative role in radiation damage of cell. The level of ROS in cells is regulated by enzymatic and nonenzymatic antioxidant systems. The most powerful ones among them are superoxide dismutases (SODs) catalyzing the dismutation of superoxide anion radical o{sub 2} to H{sub 2}O{sub 2}, catalase deactivating h-2O{sub 2} and reduced glutathion (GSH) detoxifying H{sub 2}O{sub 2} and other ROS> At the 5{sub th} day after sublethal whole body irradiation, splenocytes of irradiated mice expressed only marginally increased levels of Mn-SOD, however, Cu/Zn-SOD, catalase, thioredoxine reductase (TR) and thioredoxine (TRX) mRNA (135% increase compared to control), however, the combination of irradiation with ginsan increased the SODs and GPX production more effectively. In addition to the above results, we obtained the similar data of protein expression. The enzyme activities of SOD, catalase, and GPX of ginsan-treated and irradiated mice were significantly enhanced by 140, 115, 126% respectively, compared with those of irradiated mice. Based on these results, we propose that the induction of antioxidant enzymes of ginsan is at least in part due to its capacity to protect against radiation.

  4. Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging

    NARCIS (Netherlands)

    Yin, Zhuoran; Raj, Divya D.; Schaafsma, Wandert; van der Heijden, Roel A.; Kooistra, Susanne M.; Reijne, Aaffien C.; Zhang, Xiaoming; Moser, Jill; Brouwer, Nieske; Heeringa, Peter; Yi, Chun-Xia; van Dijk, Gertjan; Laman, Jon D.; Boddeke, Erik W. G. M.; Eggen, Bart J. L.

    2018-01-01

    Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis.

  5. Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging

    Directory of Open Access Journals (Sweden)

    Zhuoran Yin

    2018-03-01

    Full Text Available Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD or low-fat diet (LFD during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS. Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32 in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.

  6. Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging.

    Science.gov (United States)

    Yin, Zhuoran; Raj, Divya D; Schaafsma, Wandert; van der Heijden, Roel A; Kooistra, Susanne M; Reijne, Aaffien C; Zhang, Xiaoming; Moser, Jill; Brouwer, Nieske; Heeringa, Peter; Yi, Chun-Xia; van Dijk, Gertjan; Laman, Jon D; Boddeke, Erik W G M; Eggen, Bart J L

    2018-01-01

    Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD) or low-fat diet (LFD) during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS). Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake) on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32) in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.

  7. Dietary antioxidant synergy in chemical and biological systems.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan

    2017-07-24

    Antioxidant (AOX) synergies have been much reported in chemical ("test-tube" based assays focusing on pure chemicals), biological (tissue culture, animal and clinical models), and food systems during the past decade. Tentative synergies differ from each other due to the composition of AOX and the quantification methods. Regeneration mechanism responsible for synergy in chemical systems has been discussed. Solvent effects could contribute to the artifacts of synergy observed in the chemical models. Synergy in chemical models may hardly be relevant to biological systems that have been much less studied. Apparent discrepancies exist in understanding the molecular mechanisms in both chemical and biological systems. This review discusses diverse variables associated with AOX synergy and molecular scenarios for explanation. Future research to better utilize the synergy is suggested.

  8. Microglia are essential to masculinization of brain and behavior

    Science.gov (United States)

    Lenz, Kathryn M.; Nugent, Bridget M.; Haliyur, Rachana; McCarthy, Margaret M.

    2013-01-01

    Brain sexual differentiation in rodents results from the perinatal testicular androgen surge. In the preoptic area (POA), estradiol aromatized from testosterone upregulates the production of the proinflammatory molecule, prostaglandin E2 (PGE2) to produce sex-specific brain development. PGE2 produces a two-fold greater density of dendritic spines in males than in females and masculinizes adult copulatory behavior. One neonatal dose of PGE2 masculinizes the POA and behavior, and simultaneous treatment with an inhibitor of additional prostaglandin synthesis prevents this masculinization, indicating a positive feed-forward process that leads to sustained increases in PGE2. The mechanisms underlying this feed-forward process were unknown. Microglia, the primary immunocompetent cells in the brain, are active neonatally, contribute to normal brain development, and both produce and respond to prostaglandins. We investigated whether there are sex differences in microglia in the POA and whether they influence developmental masculinization. Neonatal males had twice as many ameboid microglia as females and a more activated morphological profile, and both estradiol and PGE2 masculinized microglial number and morphology in females. Microglial inhibition during the critical period for sexual differentiation prevented sex differences in microglia, estradiol-induced masculinization of dendritic spine density, and adult copulatory behavior. Microglial inhibition also prevented the estradiol-induced upregulation of PGE2, indicating that microglia are essential to the feed-forward process through which estradiol upregulates prostaglandin production. These studies demonstrate that immune cells in the brain interact with the nervous and endocrine systems during development, and are crucial for sexual differentiation of brain and behavior. PMID:23407936

  9. Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan

    Directory of Open Access Journals (Sweden)

    Tuan Leng Tay

    2018-01-01

    Full Text Available Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance, and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD, hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs, and obsessive-compulsive disorder (OCD or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD, bipolar disorder (BD, schizophrenia, eating disorders and sleep disorders. Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer’s and Parkinson’s. Taking into account the recent identification of

  10. Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan.

    Science.gov (United States)

    Tay, Tuan Leng; Béchade, Catherine; D'Andrea, Ivana; St-Pierre, Marie-Kim; Henry, Mathilde S; Roumier, Anne; Tremblay, Marie-Eve

    2017-01-01

    Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer's and Parkinson's). Taking into account the recent identification of microglia

  11. Innate immune functions of microglia isolated from human glioma patients

    Directory of Open Access Journals (Sweden)

    Grimm Elizabeth

    2006-03-01

    Full Text Available Abstract Background Innate immunity is considered the first line of host defense and microglia presumably play a critical role in mediating potent innate immune responses to traumatic and infectious challenges in the human brain. Fundamental impairments of the adaptive immune system in glioma patients have been investigated; however, it is unknown whether microglia are capable of innate immunity and subsequent adaptive anti-tumor immune responses within the immunosuppressive tumor micro-environment of human glioma patients. We therefore undertook a novel characterization of the innate immune phenotype and function of freshly isolated human glioma-infiltrating microglia (GIM. Methods GIM were isolated by sequential Percoll purification from patient tumors immediately after surgical resection. Flow cytometry, phagocytosis and tumor cytotoxicity assays were used to analyze the phenotype and function of these cells. Results GIM expressed significant levels of Toll-like receptors (TLRs, however they do not secrete any of the cytokines (IL-1β, IL-6, TNF-α critical in developing effective innate immune responses. Similar to innate macrophage functions, GIM can mediate phagocytosis and non-MHC restricted cytotoxicity. However, they were statistically less able to mediate tumor cytotoxicity compared to microglia isolated from normal brain. In addition, the expression of Fas ligand (FasL was low to absent, indicating that apoptosis of the incoming lymphocyte population may not be a predominant mode of immunosuppression by microglia. Conclusion We show for the first time that despite the immunosuppressive environment of human gliomas, GIM are capable of innate immune responses such as phagocytosis, cytotoxicity and TLR expression but yet are not competent in secreting key cytokines. Further understanding of these innate immune functions could play a critical role in understanding and developing effective immunotherapies to malignant human gliomas.

  12. Benfotiamine attenuates inflammatory response in LPS stimulated BV-2 microglia.

    Science.gov (United States)

    Bozic, Iva; Savic, Danijela; Laketa, Danijela; Bjelobaba, Ivana; Milenkovic, Ivan; Pekovic, Sanja; Nedeljkovic, Nadezda; Lavrnja, Irena

    2015-01-01

    Microglial cells are resident immune cells of the central nervous system (CNS), recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine) derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70 (Hsp70), tumor necrosis factor alpha α (TNF-α), interleukin-6 (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10) production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus. Therefore, benfotiamine may

  13. The response of antioxidant systems in Nostoc sphaeroides against UV-B radiation and the protective effects of exogenous antioxidants

    Science.gov (United States)

    Wang, Gaohong; Hu, Chunxiang; Li, Dunhai; Zhang, Delu; Li, Xiaoyan; Chen, Kun; Liu, Yongding

    UV radiation is one of many harmful factors found in space that are detrimental to organisms on earth in space exploration. In the present work, we examined the role of antioxidant system in Nostoc sphaeroides Kütz (Cyanobacterium) and the effects of exogenously applied antioxidant molecules on its photosynthetic rate under UV-B radiation. It was found that UV-B radiation promoted the activity of antioxidant system to protect photosystem II (PSII) and exogenously applied antioxidant: sodium nitroprusside (SNP) and N-acetylcysteine (NAC) had an obvious protection on PSII activity under UV-B radiation. The activity of superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), peroxidase (POD, EC 1.11.1.7) and content of MDA (malondialdehyde) and ASC (ascorbate) were improved by 0.5 mM and 1 mM SNP, but 0.1 mM SNP decreased the activity of antioxidant system. Addition of exogenous NAC decreased the activity of SOD, POD, CAT and the content MDA and ASC. In contrast, exogenously applied NAC increased GSH content. The results suggest that exogenous SNP and NAC may protect algae by different mechanisms: SNP may play double roles as both sources of reactive free radicals as well as ROS scavengers in mediating the protective role of PSII on algae under UV-B radiation. On the other hand, NAC functions as an antioxidant or precursor of glutathione, which could protect PSII directly from UV-B radiation.

  14. Learned helplessness activates hippocampal microglia in rats: A potential target for the antidepressant imipramine.

    Science.gov (United States)

    Iwata, Masaaki; Ishida, Hisahito; Kaneko, Koichi; Shirayama, Yukihiko

    An accumulating body of evidence has demonstrated that inflammation is associated with the pathology of depression. We recently found that psychological stress induces inflammation in the hippocampus of the rat brain through the inflammasome, a component of the innate immune system. Microglia, the resident macrophages in the brain, play a central role in the innate immune system and express inflammasomes; thus, we hypothesized that hippocampal microglia would be key mediators in the development of depression via stress-induced inflammation. To test this hypothesis and to determine how antidepressants modulate microglial function, we used immunohistochemistry to examine the morphological changes that occur in the hippocampal microglia of rats exposed to the learned helplessness (LH) paradigm. We noted significantly increased numbers of activated microglia in the granule cell layer, hilus, CA1, and CA3 regions of the hippocampi of LH rats. Conversely, administering imipramine to LH rats for 7days produced a significant decrease in the number of activated microglia in the hilus, but not in the other examined regions. Nonetheless, there were no significant differences in the combined number of activated and non-activated microglia either in LH or LH+imipramine rats relative to control rats. In addition, treating the naïve rats with imipramine or fluvoxamine produced no discernible microglial changes. These data suggest that stress activates hippocampal microglia, while certain antidepressants decrease the number of activated microglia in the hilus, but not in other hippocampal regions. Therefore, the hilus represents a candidate target region for the antidepressant imipramine. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Protective microglia and its regulation in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Weidong Le

    2016-09-01

    Full Text Available Microglia mediated neuroinflammation is a hallmark of Parkinson’s disease (PD. It has been reported that microglia in the brain of PD have both neurotoxic and neuroprotective effects, depending on the microglial activation states. In this review, we will focus on the recent research findings of the neuroprotective role of microglia-mediated neuroinflammation in PD. Accumulating new evidences have indicated that the protective mechanisms of microglia may result from its regulation of transrepression pathways via nuclear receptors, anti-inflammatory responses, neuron-microglia crosstalk, histone modification and microRNA regulation. All of these protective mechanisms of microglia orchestrate with each other to repress the production of neurotoxic inflammatory components. Since the detrimental effects of inflammation overwhelm the protective effects of microglia during the disease progression of PD, exploring an in-depth understanding of the protective mechanisms of microglia and promoting the transformation of beneficial microglia are urgently important for the treatment of PD.

  16. Priming of microglia in a DNA-repair deficient model of accelerated aging.

    Science.gov (United States)

    Raj, Divya D A; Jaarsma, Dick; Holtman, Inge R; Olah, Marta; Ferreira, Filipa M; Schaafsma, Wandert; Brouwer, Nieske; Meijer, Michel M; de Waard, Monique C; van der Pluijm, Ingrid; Brandt, Renata; Kreft, Karim L; Laman, Jon D; de Haan, Gerald; Biber, Knut P H; Hoeijmakers, Jan H J; Eggen, Bart J L; Boddeke, Hendrikus W G M

    2014-09-01

    Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microglia is enhanced sensitivity to inflammatory stimuli, referred to as priming. It is unclear if priming is due to intrinsic microglia ageing or induced by the ageing neural environment. We have studied this in Ercc1 mutant mice, a DNA repair-deficient mouse model that displays features of accelerated aging in multiple tissues including the CNS. In Ercc1 mutant mice, microglia showed hallmark features of priming such as an exaggerated response to peripheral lipopolysaccharide exposure in terms of cytokine expression and phagocytosis. Specific targeting of the Ercc1 deletion to forebrain neurons resulted in a progressive priming response in microglia exemplified by phenotypic alterations. Summarizing, these data show that neuronal genotoxic stress is sufficient to switch microglia from a resting to a primed state. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Isolation of primary microglia from the human post-mortem brain: effects of ante- and post-mortem variables.

    Science.gov (United States)

    Mizee, Mark R; Miedema, Suzanne S M; van der Poel, Marlijn; Adelia; Schuurman, Karianne G; van Strien, Miriam E; Melief, Jeroen; Smolders, Joost; Hendrickx, Debbie A; Heutinck, Kirstin M; Hamann, Jörg; Huitinga, Inge

    2017-02-17

    Microglia are key players in the central nervous system in health and disease. Much pioneering research on microglia function has been carried out in vivo with the use of genetic animal models. However, to fully understand the role of microglia in neurological and psychiatric disorders, it is crucial to study primary human microglia from brain donors. We have developed a rapid procedure for the isolation of pure human microglia from autopsy tissue using density gradient centrifugation followed by CD11b-specific cell selection. The protocol can be completed in 4 h, with an average yield of 450,000 and 145,000 viable cells per gram of white and grey matter tissue respectively. This method allows for the immediate phenotyping of microglia in relation to brain donor clinical variables, and shows the microglia population to be distinguishable from autologous choroid plexus macrophages. This protocol has been applied to samples from over 100 brain donors from the Netherlands Brain Bank, providing a robust dataset to analyze the effects of age, post-mortem delay, brain acidity, and neurological diagnosis on microglia yield and phenotype. Our data show that cerebrospinal fluid pH is positively correlated to microglial cell yield, but donor age and post-mortem delay do not negatively affect viable microglia yield. Analysis of CD45 and CD11b expression showed that changes in microglia phenotype can be attributed to a neurological diagnosis, and are not influenced by variation in ante- and post-mortem parameters. Cryogenic storage of primary microglia was shown to be possible, albeit with variable levels of recovery and effects on phenotype and RNA quality. Microglial gene expression substantially changed due to culture, including the loss of the microglia-specific markers, showing the importance of immediate microglia phenotyping. We conclude that primary microglia can be isolated effectively and rapidly from human post-mortem brain tissue, allowing for the study of the

  18. The role of the antioxidant system during intense endurance exercise: lessons from migrating birds.

    Science.gov (United States)

    Cooper-Mullin, Clara; McWilliams, Scott R

    2016-12-01

    During migration, birds substantially increase their metabolic rate and burn fats as fuel and yet somehow avoid succumbing to overwhelming oxidative damage. The physiological means by which vertebrates such as migrating birds can counteract an increased production of reactive species (RS) are rather limited: they can upregulate their endogenous antioxidant system and/or consume dietary antioxidants (prophylactically or therapeutically). Thus, birds can alter different components of their antioxidant system to respond to the demands of long-duration flights, but much remains to be discovered about the complexities of RS production and antioxidant protection throughout migration. Here, we use bird migration as an example to discuss how RS are produced during endurance exercise and how the complex antioxidant system can protect against cellular damage caused by RS. Understanding how a bird's antioxidant system responds during migration can lend insights into how antioxidants protect birds during other life-history stages when metabolic rate may be high, and how antioxidants protect other vertebrates from oxidative damage during endurance exercise. © 2016. Published by The Company of Biologists Ltd.

  19. A novel lung slice system with compromised antioxidant defenses

    Energy Technology Data Exchange (ETDEWEB)

    Hardwick, S.J.; Adam, A.; Cohen, G.M. (Univ. of London (England)); Smith, L.L. (Imperial Chemical Industries PLC, Cheshire (England))

    1990-04-01

    In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 {mu}M) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP{sup +}, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of {sup 14}CO{sub 2} from D-({sup 14}C(U))-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.

  20. The State of the Antioxidant System in Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Gulnozakhon Z. Aripkhodjaeva

    2014-06-01

    Full Text Available Chronic hepatitis of viral etiology ranks very high in human pathology with respect to its socio-economic and medical significance. In viral hepatitis, membrane destruction occurs via the processes of lipoperoxidation, a valid factor that triggers the mechanism of hepatocyte necrosis. The glutathione system is also involved in the first line of cell defense actions against the effect of the free radicals. In this study, 128 patients with Chronic Hepatitis C (CHC were examined. The degree of antioxidant defense was determined by the indicators of the activity of the glutathione and glutathione-dependent enzymes. The total, reduced and oxidized glutathione levels were determined by V. G. Chernishov. The activity of the glutathione-dependent enzymes, viz., glutathione peroxidase (GP, glutathione reductase (GR and glutathione transferase (GT was measured by the method prescribed by S. N. Vlasova and co-authors (1990. The results of the investigations performed revealed that in CHC patients, deep-seated disorders were observed in the glutathione system manifested by a decrease in the total glutathione levels, its oxidized and reduced forms, changes in the glutathione enzymes and the interrelationships between the intensity of the changes and the degree of the intoxication syndrome.

  1. A novel lung slice system with compromised antioxidant defenses

    International Nuclear Information System (INIS)

    Hardwick, S.J.; Adam, A.; Cohen, G.M.; Smith, L.L.

    1990-01-01

    In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 μM) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP + , and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of 14 CO 2 from D-[ 14 C(U)]-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone

  2. Toxic effects of erythromycin, ciprofloxacin and sulfamethoxazole exposure to the antioxidant system in Pseudokirchneriella subcapitata

    International Nuclear Information System (INIS)

    Nie Xiangping; Liu Binyang; Yu Huijuan; Liu Weiqiu; Yang Yufeng

    2013-01-01

    We tested antioxidant responses of the green microalga Pseudokirchneriella subcapitata exposed to different concentrations of the three antibiotics erythromycin (ETM), ciprofloxacin (CPF) and sulfamethoxazole (SMZ). Measurements included the level of lipid peroxidation, the total antioxidative capacity and three major antioxidant mechanisms: the ascorbate–glutathione cycle, the xanthophyll cycle and the enzyme activities of catalase (CAT), superoxide dismutase (SOD), guaiacol glutathione peroxidase (GPX) and glutathione-S-transferase (GST). Three antibiotics significantly affect the antioxidant system of P. subcapitata, but in different ways the alga was more tolerant to CPF and SMZ exposures than to ETM exposure. ETM caused reductions in AsA and GSH biosynthesis, ascorbate–glutathione cycle, xanthophylls cycle and antioxidant enzyme activities. The toxicity of CPF seems to be mainly overcome via induction of the ascorbate–glutathione cycle and CAT, SOD and GPX activities, while the toxicity of SMZ on the photosynthetic apparatus is predominantly reduced by the xanthophyll cycle and GST activity. - Highlights: ► Antibiotics may affect the antioxidant system of Pseudokirchneriella subcapitata. ► Erythromycin decreased AsA, GSH biosynthesis and antioxidant enzyme activities. ► Ciprofloxacin and sulfamethoxazole were lower toxic than erythromycin. - Antibiotics (Erythromycin, ciprofloxacin and sulfamethoxazole) cause the change of antioxidant system and lead to oxidative stress to a green microalga, Pseudokirchneriella subcapitata.

  3. Glucose pathways adaptation supports acquisition of activated microglia phenotype.

    Science.gov (United States)

    Gimeno-Bayón, J; López-López, A; Rodríguez, M J; Mahy, N

    2014-06-01

    With its capacity to survey the environment and phagocyte debris, microglia assume a diversity of phenotypes to respond specifically through neurotrophic and toxic effects. Although these roles are well accepted, the underlying energetic mechanisms associated with microglial activation remain largely unclear. This study investigates microglia metabolic adaptation to ATP, NADPH, H(+) , and reactive oxygen species production. To this end, in vitro studies were performed with BV-2 cells before and after activation with lipopolysaccharide + interferon-γ. Nitric oxide (NO) was measured as a marker of cell activation. Our results show that microglial activation triggers a metabolic reprogramming based on an increased glucose uptake and a strengthening of anaerobic glycolysis, as well as of the pentose pathway oxidative branch, while retaining the mitochondrial activity. Based on this energy commitment, microglial defense capacity increases rapidly as well as ribose-5-phosphate and nucleic acid formation for gene transcription, essential to ensure the newly acquired functions demanded by central nervous system signaling. We also review the role of NO in this microglial energy commitment that positions cytotoxic microglia within the energetics of the astrocyte-neuron lactate shuttle. Copyright © 2014 Wiley Periodicals, Inc.

  4. Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging.

    Science.gov (United States)

    Plaza-Zabala, Ainhoa; Sierra-Torre, Virginia; Sierra, Amanda

    2017-03-09

    Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases. Herein, we first describe the basic concepts of autophagy and its regulation, discuss key aspects for its accurate monitoring at the experimental level, and summarize the evidence linking autophagy impairment to CNS senescence and disease. We focus on acute, chronic, and autoimmunity-mediated neurodegeneration, including ischemia/stroke, Alzheimer's, Parkinson's, and Huntington's diseases, and multiple sclerosis. Next, we describe the actual and potential impact of autophagy on microglial phagocytic and inflammatory function. Thus, we provide evidence of how autophagy may affect microglial phagocytosis of apoptotic cells, amyloid-β, synaptic material, and myelin debris, and regulate the progression of age-associated neurodegenerative diseases. We also discuss data linking autophagy to the regulation of the microglial inflammatory phenotype, which is known to contribute to age-related brain dysfunction. Overall, we update the current knowledge of autophagy and microglia, and highlight as yet unexplored mechanisms whereby autophagy in microglia may contribute to CNS disease and senescence.

  5. Studies on the hepatic antioxidant defense system in λ cyhalothrin ...

    African Journals Online (AJOL)

    user

    induced oxidative stress in fresh water tilapia ... Key words: Antioxidant status, λ cyhalothrin, lipid peroxidation, Oreochromis mossambicus, oxidative stress, synthetic pyrethroid. ..... and Stress: A case history for red–sore disease in largemouth bass.

  6. Microglia energy metabolism in metabolic disorder.

    Science.gov (United States)

    Kalsbeek, Martin J T; Mulder, Laurie; Yi, Chun-Xia

    2016-12-15

    Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx. Fatty acids are another source of energy for microglia and have also been shown to strongly influence microglial immune activity. Glutamine, although possibly suitable for use as an energy substrate by microglia, has been shown to have neurotoxic effects when overloaded. Microglial fuel metabolism might be associated with microglial reactivity under different pathophysiological conditions and a microglial fuel switch may thus be the underlying cause of hypothalamic dysregulation, which is associated with obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Antioxidant system parameters in children from different follow-up groups who suffered from Chernobyl accident and their changes at application of antioxidants (vitamin E and iskador)

    International Nuclear Information System (INIS)

    Antipkyin, Yu.G.; Pochinok, T.V.; Omel'chenko, L.Yi.; Arabs'ka, L.P.; Osins'ka, L.F.; Vasyuk, O.M.

    1998-01-01

    Low-dose radiation causes changes in the lipid peroxidation-antioxidant protective system in children who frequently suffer from acute respiratory virus infections. To improve the general condition and to normalize the metabolic disturbances it is advisable to administer antioxidants (vitamin E, Iskador)

  8. The role of disorders of the prooxidant-antioxidant system in diabetes etiopathology

    Directory of Open Access Journals (Sweden)

    Małgorzata Mrowicka

    2011-08-01

    Full Text Available Chronic hyperglycemia is believed to play a pivotal role in the development of diabetic complications. It was found that hyperglycemia triggered a number of mechanisms that evoke overproduction of reactive oxygen species (ROS. Diabetes mellitus is associated with an increased level of free radicals, disturbances of the enzymatic antioxidant defense system and lower concentration of exogenous antioxidants. In consequence, these abnormalities lead to a redox imbalance called oxidative stress. The aim of the present study is to summarize the role of reactive oxygen species and changes in the antioxidant defense system in the development of diabetic complications.

  9. Benfotiamine attenuates inflammatory response in LPS stimulated BV-2 microglia.

    Directory of Open Access Journals (Sweden)

    Iva Bozic

    Full Text Available Microglial cells are resident immune cells of the central nervous system (CNS, recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS and NO; cyclooxygenase-2 (COX-2, heat-shock protein 70 (Hsp70, tumor necrosis factor alpha α (TNF-α, interleukin-6 (IL-6, whereas it increased anti-inflammatory interleukin-10 (IL-10 production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2, c-Jun N-terminal kinases (JNK and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB in the nucleus. Therefore

  10. Effects of Rhizobium inoculation on Trifolium resupinatum antioxidant system under sulfur dioxide pollution

    Directory of Open Access Journals (Sweden)

    Ladan Bayat

    2014-01-01

    Full Text Available Introduction: Plant growth stimulating rhizobacteria are beneficial bacteria that can cause resistance to various stresses in plants. One of these stresses is SO2 air pollution. SO2 is known as a strong damaging air pollutant that limits growth of plants. The aim of this study is evaluation of the effects of bacterial inoculation with native and standard Rhizobium on Persian clover root growth and antioxidants activity and capacity under air SO2 pollution. Materials and methods: In this study, 31 days plants (no-inoculated and inoculated with two strains of Rhizobium exposed to the different concentrations of SO2 (0 as a control, 0.5, 1, 1.5 and 2 ppm for 5 consecutive days and 2 hours per day. Results: Results showed different concentrations of SO2 had a significant effect on Persian clover root weight and antioxidant system. Increasing SO2 stress decreased root fresh and dry weight and antioxidant capacities (IC50 and increased antioxidant activities (I% of Persian clover leaves significantly in comparison to the control plants (under 0 ppm and increased SOD, CAT and GPX activity. Inoculation of Persian clover plants with native and standard Rhizobium increased root weight and did not show a significant effect on antioxidants activity and capacity, but interaction between Rhizobium inoculation and SO2 treatment reduced significantly the stress effects of high concentration of SO2 on root growth and antioxidants activity and capacity. In fact, level of this change of root growth and antioxidant system under SO2 pollution stress in inoculated plants was lower than in the non-inoculated plants. Discussion and conclusion: As a result, an increase in SO2 concentration caused a decrease in root weight, increase in antioxidants activity and capacity of Persian clover. Inoculation with Rhizobium strains could alleviate the effect of SO2 pollution on antioxidant system by effects on root growth.

  11. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    International Nuclear Information System (INIS)

    Kakita, Hiroki; Aoyama, Mineyoshi; Nagaya, Yoshiaki; Asai, Hayato; Hussein, Mohamed Hamed; Suzuki, Mieko; Kato, Shin; Saitoh, Shinji; Asai, Kiyofumi

    2013-01-01

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N G -monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for IAE

  12. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    Energy Technology Data Exchange (ETDEWEB)

    Kakita, Hiroki [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aoyama, Mineyoshi, E-mail: ao.mine@med.nagoya-cu.ac.jp [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Nagaya, Yoshiaki; Asai, Hayato [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Hussein, Mohamed Hamed [Neonatal Intensive Care Unit, Pediatric Hospital, Cairo University, Cairo 11559 (Egypt); Maternal and Child Health Department, VACSERA, 51 Wizaret El-Zeraa-Agouza, Giza 22311 (Egypt); Suzuki, Mieko [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Kato, Shin [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Saitoh, Shinji [Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2013-04-15

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N{sup G}-monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for

  13. Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury.

    Science.gov (United States)

    Yang, Xiaodong; Xu, Shaoqing; Qian, Yiwei; Xiao, Qin

    2017-08-01

    Microglia are the primary cells that exert immune function in the central nervous system (CNS), and accumulating evidence suggests that microglia act as key players in the initiation of neurodegenerative diseases. It is now well recognized that microglia have functional plasticity and dual phenotypes, proinflammatory M1 and anti-inflammatory M2 phenotypes. Inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for the treatment of neuroinflammation-related diseases. Resveratrol has been demonstrated to exert anti-inflammatory effects by suppressing M1 microglia activation. However, the role of resveratrol in regulating microglia polarization and the molecular mechanisms involved have not been fully clarified. In this study, we tested whether resveratrol could suppress microglia activation by promoting microglia polarization toward the M2 phenotype via PGC-1α by measuring M1 and M2 markers in vitro and in vivo. Our study demonstrated that resveratrol reduced inflammatory damage and promoted microglia polarization to the M2 phenotype in LPS-induced neuroinflammation. In addition, resveratrol ameliorated LPS-induced sickness behavior in mice. The promoting effects of resveratrol on M2 polarization were attenuated by knocking down PGC-1α. PGC-1α not only suppressed LPS-evoked M1 marker expression by inhibition of NF-κB activity but also increased M2 marker expression by coactivation of the STAT6 and STAT3 pathways. We propose that overexpression PGC-1α by resveratrol could be a potential therapeutic approach to suppress neuroinflammation by regulating microglia polarization. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Physiological antioxidant system and oxidative stress in stomach cancer patients with normal renal and hepatic function

    Directory of Open Access Journals (Sweden)

    E Prabhakar Reddy

    2010-04-01

    Full Text Available Role of free radicals has been proposed in the pathogenesis of many diseases. Gastric cancer is a common disease worldwide, and leading cause of cancer death in India. Severe oxidative stress produces reactive oxygen species (ROS and induces uncontrolled lipid peroxidation. Albumin, uric acid (UA and Bilirubin are important physiological antioxidants. We aimed to evaluate and assess the role of oxidative stress (OS and physiological antioxidant system in stomach cancer patients. Lipid peroxidation measured as plasma Thio Barbituric Acid Reactive substances (TBARS, was found to be elevated significantly (p=0.001 in stomach cancer compared to controls along with a decrease in plasma physiological antioxidant system. The documented results were due to increased lipid peroxidation and involvement of physiological antioxidants in scavenging free radicals but not because of impaired hepatic and renal functions.

  15. Antioxidant Effect of Seaweed Extracts in Vitro and in Food Emulsion Systems Enriched With Fish Oil

    DEFF Research Database (Denmark)

    Larsen, Ditte Baun; Farvin, Sabeena; Jacobsen, Charlotte

    Natural antioxidants derived from marine algae have a high content of bioactive components with potential for improving oxidative stability of lipids in food systems. Bioactive components like polyphenols have been identified in marine algae. In this presentation we will discuss results from our...... ongoing work on the brown algae Fucus vesiculosus. This seaweed contains a wide range of polyphenols with potential antioxidant activity. Thus, in vitro antioxidant properties of F. vesiculosus extracts have been found to be related to the total polyphenolic content. It has been suggested that the primary...... antioxidant activity comes from secondary metabolites such as phlorotannins, a dominant polyphenolic compound. However, studies on the effectiveness of seaweed extracts in food model systems are sparse, therefore there is a need to look further into this area. Results obtained in our lab with different...

  16. NADPH oxidases in Microglia oxidant production

    DEFF Research Database (Denmark)

    Haslund-Vinding, J; McBean, G; Jaquet, V

    2017-01-01

    inhibitors. Finally, we review the recent literature on NOX and other sources of ROS that are involved in activation of the inflammasome and discuss the potential influence of microglia-derived oxidants on neurogenesis, neural differentiation and culling of surplus progenitor cells. The degree to which...

  17. Microglia Modulate Wiring of the Embryonic Forebrain

    Directory of Open Access Journals (Sweden)

    Paola Squarzoni

    2014-09-01

    Full Text Available Dysfunction of microglia, the tissue macrophages of the brain, has been associated with the etiology of several neuropsychiatric disorders. Consistently, microglia have been shown to regulate neurogenesis and synaptic maturation at perinatal and postnatal stages. However, microglia invade the brain during mid-embryogenesis and thus could play an earlier prenatal role. Here, we show that embryonic microglia, which display a transiently uneven distribution, regulate the wiring of forebrain circuits. Using multiple mouse models, including cell-depletion approaches and cx3cr1−/−, CR3−/−, and DAP12−/− mutants, we find that perturbing microglial activity affects the outgrowth of dopaminergic axons in the forebrain and the laminar positioning of subsets of neocortical interneurons. Since defects in both dopamine innervation and cortical networks have been linked to neuropsychiatric diseases, our study provides insights into how microglial dysfunction can impact forebrain connectivity and reveals roles for immune cells during normal assembly of brain circuits.

  18. Neuroprotective function for ramified microglia in hippocampal excitotoxicity

    Directory of Open Access Journals (Sweden)

    Vinet Jonathan

    2012-01-01

    Full Text Available Abstract Background Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. Methods Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia. Results Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA. Conclusions Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.

  19. Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia.

    Science.gov (United States)

    Delgado, R; Carlin, A; Airaghi, L; Demitri, M T; Meda, L; Galimberti, D; Baron, P; Lipton, J M; Catania, A

    1998-06-01

    Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin-derived amino acid sequences that include alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of alpha-MSH (1-13), alpha-MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon gamma (IFN-gamma). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-gamma, microglia increased release of alpha-MSH. Production of TNF-alpha, IL-6, and NO was greater in activated microglia after innmunoneutralization of endogenous alpha-MSH. The results suggest that alpha-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.

  20. Brucella abortus-activated microglia induce neuronal death through primary phagocytosis.

    Science.gov (United States)

    Rodríguez, Ana M; Delpino, M Victoria; Miraglia, M Cruz; Costa Franco, Miriam M; Barrionuevo, Paula; Dennis, Vida A; Oliveira, Sergio C; Giambartolomei, Guillermo H

    2017-07-01

    Inflammation has long been implicated as a contributor to pathogenesis in neurobrucellosis. Many of the associated neurocognitive symptoms of neurobrucellosis may be the result of neuronal dysfunction resulting from the inflammatory response induced by Brucella abortus infection in the central nervous system. In this manuscript, we describe an immune mechanism for inflammatory activation of microglia that leads to neuronal death upon B. abortus infection. B. abortus was unable to infect or harm primary cultures of mouse neurons. However, when neurons were co-cultured with microglia and infected with B. abortus significant neuronal loss occurred. This phenomenon was dependent on TLR2 activation by Brucella lipoproteins. Neuronal death was not due to apoptosis, but it was dependent on the microglial release of nitric oxide (NO). B. abortus infection stimulated microglial proliferation, phagocytic activity and engulfment of neurons. NO secreted by B. abortus-activated microglia induced neuronal exposure of the "eat-me" signal phosphatidylserine (PS). Blocking of PS-binding to protein milk fat globule epidermal growth factor-8 (MFG-E8) or microglial vitronectin receptor-MFG-E8 interaction was sufficient to prevent neuronal loss by inhibiting microglial phagocytosis without affecting their activation. Taken together, our results indicate that B. abortus is not directly toxic to neurons; rather, these cells become distressed and are killed by phagocytosis in the inflammatory surroundings generated by infected microglia. Neuronal loss induced by B. abortus-activated microglia may explain, in part, the neurological deficits observed during neurobrucellosis. © 2017 Wiley Periodicals, Inc.

  1. Are microglia minding us? Digging up the unconscious mind-brain relationship from a neuropsychoanalytic approach.

    Directory of Open Access Journals (Sweden)

    Takahiro A. Kato

    2013-02-01

    Full Text Available The unconscious mind-brain relationship remains unresolved. From the perspective of neuroscience, neuronal networks including synapses have been dominantly believed to play crucial roles in human mental activities, while glial contribution to mental activities has long been ignored. Recently, it has been suggested that microglia, glial cells with immunological/inflammatory functions, play important roles in psychiatric disorders. Newly revealed microglial roles, such as constant direct contact with synapses even in normal brain, have defied the common traditional belief that microglia do not contribution to neuronal networks. Recent human neuroeconomic investigations with healthy volunteers using minocycline, an antibiotic with inhibitory effects on microglial activation, suggest that microglia may unconsciously modulate human social behaviors as noise.We herein propose a novel unconscious mind structural system in the brain centering on microglia from a neuropsychoanalytic approach. At least to some extent, microglial activation in the brain may activate unconscious drives as psychological immune memory/reaction in the mind, and result in various emotions, traumatic reactions, psychiatric symptoms including suicidal behaviors, and (psychoanalytic transference during interpersonal relationships. Microglia have the potential to bridge the huge gap between neuroscience, biological psychiatry, psychology and psychoanalysis as a key player to connect the conscious and the unconscious world.

  2. Oxidative stress and the antioxidant enzyme system in the developing brain

    Directory of Open Access Journals (Sweden)

    So-Yeon Shim

    2013-03-01

    Full Text Available Preterm infants are vulnerable to the oxidative stress due to the production of large amounts of free radicals, antioxidant system insufficiency, and immature oligodendroglial cells. Reactive oxygen species (ROS play a pivotal role in the development of periventricular leukomalacia. The three most common ROS are superoxide (O2&#8226;-, hydroxyl radical (OH&#8226;, and hydrogen peroxide (H2O2. Under normal physiological conditions, a balance is maintained between the production of ROS and the capacity of the antioxidant enzyme system. However, if this balance breaks down, ROS can exert toxic effects. Superoxide dismutase, glutathione peroxidase, and catalase are considered the classical antioxidant enzymes. A recently discovered antioxidant enzyme family, peroxiredoxin (Prdx, is also an important scavenger of free radicals. Prdx1 expression is induced at birth, whereas Prdx2 is constitutively expressed, and Prdx6 expression is consistent with the classical antioxidant enzymes. Several antioxidant substances have been studied as potential therapeutic agents; however, further preclinical and clinical studies are required before allowing clinical application.

  3. Intracellular antioxidants dissolve man-made antioxidant nanoparticles: using redox vulnerability of nanoceria to develop a responsive drug delivery system.

    Science.gov (United States)

    Muhammad, Faheem; Wang, Aifei; Qi, Wenxiu; Zhang, Shixing; Zhu, Guangshan

    2014-01-01

    Regeneratable antioxidant property of nanoceria has widely been explored to minimize the deleterious influences of reactive oxygen species. Limited information is, however, available regarding the biological interactions and subsequent fate of nanoceria in body fluids. This study demonstrates a surprising dissolution of stable and ultrasmall (4 nm) cerium oxide nanoparticles (CeO2 NPs) in response to biologically prevalent antioxidant molecules (glutathione, vitamin C). Such a redox sensitive behavior of CeO2 NPs is subsequently exploited to design a redox responsive drug delivery system for transporting anticancer drug (camptothecin). Upon exposing the CeO2 capped and drug loaded nanoconstruct to vitamin c or glutathione, dissolution-accompanied aggregation of CeO2 nanolids unleashes the drug molecules from porous silica to achieve a significant anticancer activity. Besides stimuli responsive drug delivery, immobilization of nanoceria onto the surface of mesoporous silica also facilitates us to gain a basic insight into the biotransformation of CeO2 in physiological mediums.

  4. In Vivo Imaging of Microglia Turnover in the Mouse Retina After Ionizing Radiation and Dexamethasone Treatment

    DEFF Research Database (Denmark)

    Alt, C.; Runnels, J. M.; Mortensen, L. J.

    2014-01-01

    irradiation with a confocal scanning laser ophthalmoscope that we custom-built specifically for multicolor imaging of the murine retina. RESULTS. Ionizing radiation resulted in loss of 75% of the resident retinal microglia population after 70 days. Recruitment of BMDCs was delayed with respect...... dexamethasone preserves resident microglia and minimizes recruitment of BMDCs after ionizing radiation exposure and BMT.......PURPOSE. Gamma irradiation and bone marrow transplantation (BMT) are established clinical procedures for the treatment of hematologic malignancies. The radiation targets cells in the bone marrow, but injury to other tissues, including the central nervous system (CNS), have been reported. Here, we...

  5. Phytotoxicity of pesticides mancozeb and chlorpyrifos: correlation with the antioxidative defence system in Allium cepa.

    Science.gov (United States)

    Fatma, Firdos; Verma, Sonam; Kamal, Aisha; Srivastava, Alka

    2018-02-01

    Pesticides are a group of chemical substances which are widely used to improve agricultural production. However, these substances could be persistent in soil and water, accumulative in sediment or bio-accumulative in biota depending on their solubility, leading to different types of environmental pollution. The present study was done to assess the impact of pesticides-mancozeb and chlorpyrifos, via morphological and physiological parameters using Allium cepa test system. Phytotoxic effects of pesticides were examined via germination percentage, survival percentage, root and shoot length, root shoot length ratio, seedling vigor index, percentage of phytotoxicity and tolerance index. Oxidative stress on Allium seedlings caused by pesticides was also assessed by investigating the activity of antioxidative enzymes viz. catalase, peroxidase and superoxide dismutase. Correlation was worked out between morphological parameters and antioxidative enzymes to bring out the alliance between them. Mancozeb and chlorpyrifos concentrations were significantly and positively correlated with the activity of antioxidative enzymes and negatively correlated with morphological parameters. Significant positive correlation between various morphological parameters showed their interdependency. However, negative correlation was obtained between activity of antioxidative enzymes and morphological parameters. The enzymes however, showed positive correlation with each other. Based on our result we can conclude that all morphological parameters were adversely affected by the two pesticides as reflected by phytotoxicity in Allium . Their negative correlation with activity of antioxidative enzymes indicates that upregulation of antioxidative enzymes is not sufficient to overcome the toxic effect, thereby signifying the threat being caused by the regular use of these pesticides.

  6. Microglia and neuroprotection: implications for Alzheimer's disease.

    Science.gov (United States)

    Streit, Wolfgang J

    2005-04-01

    The first part of this paper summarizes some of the key observations from experimental work in animals that support a role of microglia as neuroprotective cells after acute neuronal injury. These studies point towards an important role of neuronal-microglial crosstalk in the facilitation of neuroprotection. Conceptually, injured neurons are thought to generate rescue signals that trigger microglial activation and, in turn, activated microglia produce trophic or other factors that help damaged neurons recover from injury. Against this background, the second part of this paper summarizes recent work from postmortem studies conducted in humans that have revealed the occurrence of senescent, or dystrophic, microglial cells in the aged and Alzheimer's disease brain. These findings suggest that microglial cells become increasingly dysfunctional with advancing age and that a loss of microglial cell function may involve a loss of neuroprotective properties that could contribute to the development of aging-related neurodegeneration.

  7. The antioxidant system of seminal fluid during in vitro storage of sterlet Acipenser ruthenus sperm.

    Science.gov (United States)

    Dzyuba, Viktoriya; Cosson, Jacky; Dzyuba, Borys; Yamaner, Gunes; Rodina, Marek; Linhart, Otomar

    2016-04-01

    The role of the seminal fluid antioxidant system in protection against damage to spermatozoa during in vitro sperm storage is unclear. This study investigated the effect of in vitro storage of sterlet Acipenser ruthenus spermatozoa together with seminal fluid for 36 h at 4 °C on spermatozoon motility rate and curvilinear velocity, thiobarbituric acid reactive substance level, and components of enzyme and non-enzyme antioxidant system (superoxide dismutase and catalase activity and uric acid concentration) in seminal fluid. Spermatozoon motility parameters after sperm storage were significantly decreased, while the level of thiobarbituric acid reactive substances, activity of superoxide dismutase and catalase, and uric acid concentration did not change. Our findings suggest that the antioxidant system of sterlet seminal fluid is effective in preventing oxidative stress during short-term sperm storage and prompt future investigations of changes in spermatozoon homeostasis and in spermatozoon plasma membrane structure which are other possible reasons of spermatozoon motility deterioration upon sperm storage.

  8. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

    Energy Technology Data Exchange (ETDEWEB)

    Dannhausen, Katharina; Karlstetter, Marcus; Caramoy, Albert [Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne (Germany); Volz, Cornelia; Jägle, Herbert [Department of Ophthalmology, University Hospital Regensburg, Regensburg (Germany); Liebisch, Gerhard [Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg (Germany); Utermöhlen, Olaf [Institute for Medical Microbiology, Immunology and Hygiene and Center for Molecular Medicine Cologne, University of Cologne, Cologne (Germany); Langmann, Thomas, E-mail: thomas.langmann@uk-koeln.de [Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne (Germany)

    2015-08-21

    Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice. • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.

  9. Modification of antioxidant systems in cell walls of maize roots by different nitrogen sources

    International Nuclear Information System (INIS)

    Hadži-Tašković Šukalović V; Vuletić, M.; Marković, K.; Željko, Vučinić; Kravić, N.

    2016-01-01

    Antioxidant systems of maize root cell walls grown on different nitrogen sources were evaluated. Plants were grown on a medium containing only NO3- or the mixture of NO3-+NH4+, in a 2:1 ratio. Eleven-day old plants, two days after the initiation of lateral roots, were used for the experiments. Cell walls were isolated from lateral roots and primary root segments, 2-7 cm from tip to base, representing zones of intense or decreased growth rates, respectively. Protein content and the activity of enzymes peroxidase, malate dehydrogenase and ascorbate oxidase ionically or covalently bound to the walls, as well as cell wall phenolic content and antioxidant capacity, were determined. Cell walls of plants grown on mixed N possess more developed enzymatic antioxidant systems and lower non-enzymatic antioxidant defenses than cell walls grown on NO3-. Irrespective of N treatment, the activities of all studied enzymes and protein content were higher in cell walls of lateral compared to primary roots. Phenolic content of cell walls isolated from lateral roots was higher in NO3--grown than in mixed N grown plants. No significant differences could be observed in the isozyme patterns of cell wall peroxidases isolated from plants grown on different nutrient solution. Our results indicate that different N treatments modify the antioxidant systems of root cell walls. Treatment with NO3- resulted in an increase of constitutive phenolic content, while the combination of NO3-+NH4+ elevated the redox enzyme activities in root cell walls.

  10. Modification of antioxidant systems in cell walls of maize roots by different nitrogen sources

    Energy Technology Data Exchange (ETDEWEB)

    Hadži-Tašković Šukalović V; Vuletić, M.; Marković, K.; Željko, Vučinić; Kravić, N.

    2016-07-01

    Antioxidant systems of maize root cell walls grown on different nitrogen sources were evaluated. Plants were grown on a medium containing only NO3- or the mixture of NO3-+NH4+, in a 2:1 ratio. Eleven-day old plants, two days after the initiation of lateral roots, were used for the experiments. Cell walls were isolated from lateral roots and primary root segments, 2-7 cm from tip to base, representing zones of intense or decreased growth rates, respectively. Protein content and the activity of enzymes peroxidase, malate dehydrogenase and ascorbate oxidase ionically or covalently bound to the walls, as well as cell wall phenolic content and antioxidant capacity, were determined. Cell walls of plants grown on mixed N possess more developed enzymatic antioxidant systems and lower non-enzymatic antioxidant defenses than cell walls grown on NO3-. Irrespective of N treatment, the activities of all studied enzymes and protein content were higher in cell walls of lateral compared to primary roots. Phenolic content of cell walls isolated from lateral roots was higher in NO3--grown than in mixed N grown plants. No significant differences could be observed in the isozyme patterns of cell wall peroxidases isolated from plants grown on different nutrient solution. Our results indicate that different N treatments modify the antioxidant systems of root cell walls. Treatment with NO3- resulted in an increase of constitutive phenolic content, while the combination of NO3-+NH4+ elevated the redox enzyme activities in root cell walls.

  11. [Formation of the compensation answer in the system "lipid peroxidation - antioxidant protection" in rats with alimentary dislipidemia].

    Science.gov (United States)

    Karaman, Iu K; Novgorodtseva, T P; Vitkina, T I; Lobanova, E G

    2011-01-01

    It is investigated conditions of system "lipid peroksidation - antioxidant protection" at rats of the line Wistar at prolonged formation alimentary dyslipidemia (DLP). It is established, that at formation DLP during 46 days in cells there was no increase in resistance and capacity of processes antioxidant protection. In prolonged DLP (90 days) was characterized by occurrence of the compensation-adaptive answer in the system "lipid peroksidation - antioxidant protection".

  12. Bone marrow-derived microglia infiltrate into the paraventricular nucleus of chronic psychological stress-loaded mice.

    Directory of Open Access Journals (Sweden)

    Koji Ataka

    Full Text Available BACKGROUND: Microglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow. METHODS AND FINDINGS: Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1(lowCCR2(+CXCR4(high, as distinct from CX3CR1(highCCR2(-CXCR4(low resident microglia, and express higher levels of interleukin-1β (IL-1β but lower levels of tumor necrosis factor-α (TNF-α. Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1 in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1 in the bone marrow and increases the frequency of CXCR4(+ monocytes in peripheral circulation. And then a chemokine (C-C motif receptor 2 (CCR2 or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN. CONCLUSION: Chronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.

  13. Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

    International Nuclear Information System (INIS)

    Wang, Cheng; Nie, Xiaoke; Zhang, Yan; Li, Ting; Mao, Jiamin; Liu, Xinhang; Gu, Yiyang; Shi, Jiyun; Xiao, Jing; Wan, Chunhua; Wu, Qiyun

    2015-01-01

    Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

  14. Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng; Nie, Xiaoke; Zhang, Yan [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Li, Ting; Mao, Jiamin [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Liu, Xinhang [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Gu, Yiyang; Shi, Jiyun [Department of Labor and Environmental Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Xiao, Jing [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wan, Chunhua [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wu, Qiyun, E-mail: wqy@ntu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)

    2015-10-15

    Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis. - Highlights: • PFOS exposure induced expression of iNOS and production of NO in HAPI microglia. • PFOS induced the production of ROS in HAPI microglia. • ERK/JNK MAPK pathways were activated following PFOS exposure in HAPI microglia. • NO released by HAPI microglia participated in the apoptosis of SH-SY5Y cells.

  15. Antioxidant system for the preservation of vitamin A in Ultra Rice.

    Science.gov (United States)

    Li, Yao Olive; Lam, Jane; Diosady, Levente L; Jankowski, Shirley

    2009-03-01

    Ultra Rice grains are micronutrient-fortified, extruded rice grains designed to address specific nutritional deficiencies in populations where rice is a staple food. Vitamin A and some of the B vitamins, as well as iron and zinc, are target nutrients for fortification through Ultra Rice technology. Vitamin A is sensitive to degradation. Therefore, the original Ultra Rice formulations included stabilizers, some of which were not approved as food additives in all of the receiving markets. To develop a new antioxidant system for improving vitamin A storage stability in Ultra Rice grains, while complying with international food regulations. Ten formulations were prepared containing various combinations of hydrophilic and hydrophobic antioxidants, as well as moisture stabilizers. Accelerated vitamin A storage stability tests were conducted at 25 degrees, 35 degrees, and 45 degrees C with 70% to 100% relative humidity. The most stable samples contained one or more phenolic antioxidants, a water-soluble antioxidant, and stabilizing agents. The best results were obtained by using butylated hydroxyanisole (BHA) in combination with butylated hydroxytoluene (BHT) as the hydrophobic antioxidants and ascorbic acid as the hydrophilic antioxidant. Citric acid and sodium tripolyphosphate (STPP) were used to chelate metal ions and to stabilize moisture, respectively. The best formulations retained more than 85% and approximately 70% of the added vitamin A at 25 degrees and 45 degrees C, respectively, after 24 weeks storage. The best antioxidant system, composed of generally accepted food additives, improved vitamin A stability while reducing the price, thus greatly improving the commercial viability of Ultra Rice grains for use as a ricefortificant.

  16. Selective activation of microglia in spinal cord but not higher cortical regions following nerve injury in adult mouse

    Directory of Open Access Journals (Sweden)

    Shang Yuze

    2008-04-01

    Full Text Available Abstract Neuronal plasticity along the pathway for sensory transmission including the spinal cord and cortex plays an important role in chronic pain, including inflammatory and neuropathic pain. While recent studies indicate that microglia in the spinal cord are involved in neuropathic pain, a systematic study has not been performed in other regions of the central nervous system (CNS. In the present study, we used heterozygous Cx3cr1GFP/+mice to characterize the morphological phenotypes of microglia following common peroneal nerve (CPN ligation. We found that microglia showed a uniform distribution throughout the CNS, and peripheral nerve injury selectively activated microglia in the spinal cord dorsal horn and related ventral horn. In contrast, microglia was not activated in supraspinal regions of the CNS, including the anterior cingulate cortex (ACC, prefrontal cortex (PFC, primary and secondary somatosensory cortex (S1 and S2, insular cortex (IC, amygdala, hippocampus, periaqueductal gray (PAG and rostral ventromedial medulla (RVM. Our results provide strong evidence that nerve injury primarily activates microglia in the spinal cord of adult mice, and pain-related cortical plasticity is likely mediated by neurons.

  17. Priming of microglia in a DNA-repair deficient model of accelerated aging

    NARCIS (Netherlands)

    Raj, Divya D. A.; Jaarsma, Dick; Holtman, Inge R.; Olah, Marta; Ferreira, Filipa M.; Schaafsma, Wandert; Brouwer, Nieske; Meijer, Michel M.; de Waard, Monique C.; van der Pluijm, Ingrid; Brandt, Renata; Kreft, Karim L.; Laman, Jon D.; de Haan, Gerald; Biber, Knut P. H.; Hoeijmakers, Jan H. J.; Eggen, Bart J. L.; Boddeke, Hendrikus W. G. M.

    Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of

  18. 28-Homobrassinolide mitigates boron induced toxicity through enhanced antioxidant system in Vigna radiata plants.

    Science.gov (United States)

    Yusuf, Mohammad; Fariduddin, Qazi; Ahmad, Aqil

    2011-11-01

    The objective of this study was to establish relationship between boron induced oxidative stress and antioxidant system in Vigna radiata plants and also to investigate whether brassinosteroids will enhance the level of antioxidant system that could confer tolerance to the plants from the boron induced oxidative stress. The mung bean (V. radiata cv. T-44) plants were administered with 0.50, 1.0 and 2.0 mM boron at 6 d stage for 7 d along with nutrient solution. At 13 d stage, the seedlings were sprayed with deionized water (control) or 10(-8) M of 28-homobrassinolide and plants were harvested at 21 d stage to assess growth, leaf gas-exchange traits and biochemical parameters. The boron treatments diminished growth, water relations and photosynthetic attributes along with nitrate reductase and carbonic anhydrase activity in the concentration dependent manner whereas, it enhanced lipid peroxidation, electrolyte leakage, accumulation of H(2)O(2) as well as proline, and various antioxidant enzymes in the leaves of mung bean which were more pronounced at higher concentrations of boron. However, the follow-up application of 28-homobrassinolide to the boron stressed plants improved growth, water relations and photosynthesis and further enhanced the various antioxidant enzymes viz. catalase, peroxidase and superoxide dismutase and content of proline. The elevated level of antioxidant enzymes as well as proline could have conferred tolerance to the B-stressed plants resulting in improved growth, water relations and photosynthetic attributes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Microglia: An Interface between the Loss of Neuroplasticity and Depression

    Directory of Open Access Journals (Sweden)

    Gaurav Singhal

    2017-09-01

    Full Text Available Depression has been widely accepted as a major psychiatric disease affecting nearly 350 million people worldwide. Research focus is now shifting from studying the extrinsic and social factors of depression to the underlying molecular causes. Microglial activity is shown to be associated with pathological conditions, such as psychological stress, pathological aging, and chronic infections. These are primary immune effector cells in the CNS and regulate the extensive dialogue between the nervous and the immune systems in response to different immunological, physiological, and psychological stressors. Studies have suggested that during stress and pathologies, microglia play a significant role in the disruption of neuroplasticity and have detrimental effects on neuroprotection causing neuroinflammation and exacerbation of depression. After a systematic search of literature databases, relevant articles on the microglial regulation of bidirectional neuroimmune pathways affecting neuroplasticity and leading to depression were reviewed. Although, several hypotheses have been proposed for the microglial role in the onset of depression, it is clear that all molecular pathways to depression are linked through microglia-associated neuroinflammation and hippocampal degeneration. Molecular factors such as an excess of glucocorticoids and changes in gene expression of neurotrophic factors, as well as neuro active substances secreted by gut microbiota have also been shown to affect microglial morphology and phenotype resulting in depression. This review aims to critically analyze the various molecular pathways associated with the microglial role in depression.

  20. Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro

    Directory of Open Access Journals (Sweden)

    Guo-Qing Wang

    2018-01-01

    Full Text Available Parkinson’s disease (PD is one of the most common neurodegenerative diseases characterized with a gradual loss of midbrain substantia nigra (SN dopamine (DA neurons. An excessive evidence demonstrated that microglia-mediated inflammation might be involved in the pathogenesis of PD. Thus, inhibition of neuroinflammation might possess a promising potential for PD treatment. Icariin (ICA, a single active component extracted from the Herba Epimedii, presents amounts of pharmacological properties, such as anti-inflammation, anti-oxidant, and anti-aging. Recent studies show ICA produced neuroprotection against brain dysfunction. However, the mechanisms underlying ICA-exerted neuroprotection are fully illuminated. In the present study, two different neurotoxins of 6-hydroxydopamine (6-OHDA and lipopolysaccharide (LPS-induced rat midbrain DA neuronal damage were applied to investigate the neuroprotective effects of ICA. In addition, primary rat midbrain neuron-glia co-cultures were performed to explore the mechanisms underlying ICA-mediated DA neuroprotection. In vitro data showed that ICA protected DA neurons from LPS/6-OHDA-induced DA neuronal damage and inhibited microglia activation and pro-inflammatory factors production via the suppression of nuclear factor-κB (NF-κB pathway activation. In animal results, ICA significantly reduced microglia activation and significantly attenuated LPS/6-OHDA-induced DA neuronal loss and subsequent animal behavior changes. Together, ICA could protect DA neurons against LPS- and 6-OHDA-induced neurotoxicity both in vivo and in vitro. These actions might be closely associated with the inhibition of microglia-mediated neuroinflammation.

  1. Feeding the beast: can microglia in the senescent brain be regulated by diet?

    Science.gov (United States)

    Johnson, Rodney W

    2015-01-01

    Microglial cells, resident macrophages in the central nervous system (CNS), are relatively quiescent but can respond to signals from the peripheral immune system and induce neuroinflammation. In aging, microglia tend to transition to the M1 pro-inflammatory state and become hypersensitive to messages emerging from immune-to-brain signaling pathways. Thus, whereas in younger individuals where microglia respond to signals from the peripheral immune system and induce a well-controlled neuroinflammatory response that is adaptive (e.g., when well controlled, fever and sickness behavior facilitate recovery from infection), in older individuals with an infection, microglia overreact and produce excessive levels of inflammatory cytokines causing behavioral pathology including cognitive dysfunction. Importantly, recent studies indicate a number of naturally occurring bioactive compounds present in certain foods have anti-inflammatory properties and are capable of mitigating brain microglial cells. These include, e.g., flavonoid and non-flavonoid compounds in fruits and vegetables, and n-3 polyunsaturated fatty acids (PUFA) in oily fish. Thus, dietary bioactives have potential to restore the population of microglial cells in the senescent brain to a more quiescent state. The pragmatic concept to constrain microglia through dietary intervention is significant because neuroinflammation and cognitive deficits are co-morbid factors in many chronic inflammatory diseases. Controlling microglial cell reactivity has important consequences for preserving adult neurogenesis, neuronal structure and function, and cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Targeting of the Glutathione, Thioredoxin, and Nrf2 Antioxidant Systems in Head and Neck Cancer.

    Science.gov (United States)

    Roh, Jong-Lyel; Jang, Hyejin; Kim, Eun Hye; Shin, Daiha

    2017-07-10

    The glutathione (GSH), thioredoxin (Trx), and Nrf2 systems represent a major defense against reactive oxygen species (ROS), the cellular imbalance of which in cancer promotes growth and therapeutic resistance. This study investigated whether targeting the GSH, Trx, and Nrf2 antioxidant systems effectively eliminated head and neck cancer (HNC). At high concentrations, auranofin, but not buthionine sulfoximine (BSO) alone, decreased the viability of HNC, whereas even at low concentrations, auranofin plus BSO synergized to kill HNC cells. Dual silencing of the genes for GCLM and TrxR1 induced GSH depletion, Trx activity inhibition, and ROS accumulation, synergistically killing HNC cells. Inhibition of the GSH and Trx systems resulted in activation of the Nrf2-antioxidant response element (ARE) pathway, which may result in suboptimal GSH and Trx inhibition where HNC is resistant. Genetic inhibition of Nrf2 and/or HO-1 or trigonelline enhanced growth suppression, ROS accumulation, and cell death from GSH and Trx inhibition. The in vivo effects of GSH, Trx, and Nrf2 system inhibition were confirmed in a mouse HNC xenograft model by achieving growth inhibition >60% compared with those of control. Innovations: This study is the first to show that triple inhibition of GSH, Trx, and Nrf2 pathways could be an effective method to overcome the resistance of HNC. Inhibition of the Nrf2-ARE pathway in addition to dual inhibition of the GSH and Trx antioxidant systems can effectively eliminate resistant HNC. Antioxid. Redox Signal. 27, 106-114.

  3. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid

    DEFF Research Database (Denmark)

    Meyer, Anne Merete Boye; Jacobsen, Charlotte Munch

    1996-01-01

    Meyer, A. S. & C. Jacobsen, 1996. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid, J. Food Lipids, 3, 139-147.......Meyer, A. S. & C. Jacobsen, 1996. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise: Partion of ascorbic acid, J. Food Lipids, 3, 139-147....

  4. RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems

    Directory of Open Access Journals (Sweden)

    Daiha Shin

    2017-10-01

    Condensed abstract: This study revealed a novel RITA resistant mechanism associated with the sustained induction of autophagy, p62 overexpression, and Keap1-Nrf2 antioxidant system activation. The combined treatment of RITA with the autophagy inhibitor 3-methyladenine overcomes RITA resistance via dual inhibition of autophagy and antioxidant systems in vitro and in vivo.

  5. Establishment of a ternary network system for evaluating the antioxidant fraction of Danhong injection.

    Science.gov (United States)

    Wang, Yan; Jiang, Zhenzuo; Yang, Fan; Chai, Xin; Zhu, Yan; Zhao, Xiaoya; Jiang, Miaomiao; Yang, Jing; Zhao, Buchang; Qian, Ke; Wang, Yuefei

    2016-10-01

    Oxidative stress plays a crucial role in numerous cardiovascular diseases. As an effective therapy, Danhong injection (DHI) is considered to act through an antioxidant mechanism for the treatment of cardiovascular disease. In our study, we focused on the potential contribution of the antioxidant capacity of DHI fractions (Frs) and established an innovative screening method based on a 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity assay. A ternary network evaluation system, which was constructed based on the radical scavenging activity, the area under the activity-concentration curve and the solid content of the fractions, was implemented to select the fractions that posed the greatest antioxidant effect. As a result, Frs 5-7 and Frs 17-19 were shown to exhibit superior antioxidant activity according to the regression area of the ternary network, which was >0.5. Furthermore, the active fractions were characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry combined with nuclear magnetic resonance. This study provided an effective method for the comprehensive evaluation of the antioxidant effect of DHI fractions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Contribution of galloylation and polymerization to the antioxidant activity of polyphenols in fish lipid systems.

    Science.gov (United States)

    Iglesias, Jacobo; Pazos, Manuel; Lois, Salomé; Medina, Isabel

    2010-06-23

    Polyphenolic fractions extracted from pine (Pinus pinaster) bark, grape (Vitis vinifera) pomace, and witch hazel (Hamamelis virginiana) bark were selected for investigating the influence of the number of phenolic units, polymerization, and the content of esterified galloyl residues (galloylation) on their efficacy for inhibiting lipid oxidation in fish lipid enriched foodstuffs. Experiments carried out with nongalloylated pine bark fractions with different polymerization degrees demonstrated that the number of catechin residues per molecule modulates their reducing and chelating properties in solution. In real food systems such as bulk fish oil and fish oil-in-water emulsions, the efficacy against lipid oxidation was highly dependent on the physical location of the antioxidant at the oxidative sensitive sites. The lowest polymerized fractions were the most efficient in bulk fish oil samples, whereas proanthocyanidins with an intermediate polymerization degree showed the highest activity in fish oil-in-water emulsions. Galloylation did not influence the antioxidant effectiveness of proanthocyanidins in bulk fish oils. The presence of galloyl groups favored the antioxidant activity of the polyphenols in emulsions, although results indicated that a high degree of galloylation did not improve significantly the activity found with medium galloylated proanthocyanidins. The results obtained in this research provide useful information about the relationship between structure and antioxidant activity in order to design antioxidant additives with application in fish oil-enriched functional foods.

  7. EXTRACT OF Punica granatum L.: AN ALTERNATIVE TO BHT AS AN ANTIOXIDANT IN SEMISSOLID EMULSIFIED SYSTEMS

    Directory of Open Access Journals (Sweden)

    Jéssica Tiago Tozetto

    Full Text Available Pomegranate (Punica granatum L. is a fruit which has important pharmacological activities and has been attracting attention due to its important antioxidant activity, a significant feature in relation to cosmetics. Formulations containing different concentrations of an ethanolic extract of pomegranate (0.1, 1.0 and 5.0% (w/w as an antioxidant agent showed that this is an interesting alternative for the use of natural products with biological activity. The stability and rheology of semissolid systems containing an extract of this plant were evaluated. Preliminary stability studies showed greater physico-chemical stability of the formulation, and thus it was used in an accelerated stability study, as well the quantification of total phenolic compounds and the determination of antioxidant activity. It was observed that different concentrations of the extract did not significantly influence the stability. Moreover, the formulation was found to have better stability when stored at room temperature than under heated or cooled conditions. Formulations containing 0.1 and 5.0% of extract showed more stable rheological behavior, due to the absence of a solid/liquid transition in the rheogram. Tests confirmed the high phenolic content and antioxidant activity, demonstrating the potential of this plant for use in cosmetology as an antioxidant.

  8. [Responses of antioxidation system of Cynodon dactylon to recirculated landfill leachate irrigation].

    Science.gov (United States)

    Wang, Ruyi; He, Pinjing; Shao, Liming; Zhang, Bin; Li, Guojian

    2005-05-01

    With pot experiment, this paper studied the membrane lipid peroxidation and the variations of antioxidation system in Cynodon dactylon under recirculated landfill leachate irrigation. The results showed that when irrigated with low dilution ratio ( 25%), there existed an obvious negative fect on Cynodon dactylon, i.e., the chlorophyll a/b ratio decreased, while cell membrane permeability and MDA and H2O2 contents increased, which meant that the membrane lipid peroxidation was accelerated. The contents antioxidants AsA, GSH and Car also showed the similar trend, i.e., they increased with increasing leachate dilution ratio when irrigated with low dilution ratio leachate, but decreased under medium or high dilution ratio leachate irrigation. Among three test anti-oxidative enzymes, SOD and POD activities showed a similar change test antioxidants, and POD activity was more sensitive, while CAT activity was on the contrary. The contents test antioxidants and the activities of SOD and POD were negatively and significantly correlated to MDA content, indicating that they might play an important role in preventing Cynodon dactylon from cell membrane lipid peroxdation.

  9. [Formation of antioxidant defence system of geese in embryogenesis and early postnatal ontogenesis].

    Science.gov (United States)

    Danchenko, O O; Kalytka, V V

    2002-01-01

    The features of antioxidant protection of tissues of a liver and blood of the gooses in embriogenesis and early postnatal ontogenesis are found out. Maximal contents TBA active products both in a liver, and in a blood are observed in 28 diurnal embriones. Is shown, that in a liver the activity of basic antioxidant enzymes (superoxide dismutases, catalase and glutathione peroxidase) in a liver is developed already at early stages embriogenesis and is considerably enlarged in the end embriogenesis. The becoming of enzymatic system of a blood descends much more slower.

  10. Impact of reactive oxygen species on antioxidant capacity of male reproductive system.

    Science.gov (United States)

    Riaz, Muhammad; Mahmood, Zahed; Shahid, Muhammad; Saeed, M Usman Qamar; Tahir, Imtiaz Mahmood; Shah, Sm Ali; Munir, Naveed; El-Ghorab, Ahmed

    2016-09-01

    The present research work was aimed to study the mutual interaction of reactive oxygen species (ROS) and basal cells antioxidant capacity in the male reproductive system and to further establish the association between selected heavy metals and stress markers. Total oxidant status (TOS) and total antioxidant status (TAS) of serum and seminal plasma were determined by automated photometric methods. The concentrations of Selenium (Se), Lead (Pb), and Cadmium (Cd) were determined by using atomic absorption spectrophotometer. The TOS was increased significantly (P male infertility. © The Author(s) 2015.

  11. Consequences for central nervous system functional state of exposure to ionizing radiation modification with antioxidants

    International Nuclear Information System (INIS)

    Tukalenko, Je.V.; Varets'kij, V.V.; Rakochyi, O.G.; Dmyitryijeva, Yi.R.

    2004-01-01

    Aim: to estimate the pattern of ionizing radiation effects modification by antioxidants using central nervous system functional state indices. The studies were carried out using 84 rats. Beta-carotene and alpha-tocopherol were found to significantly improve conditioned activity indices level of the animals exposed to ionizing radiation and emotional-pain stress

  12. Development of new antioxidant systems for frying oil and omega-3 oils

    Science.gov (United States)

    The development of natural antioxidant systems for frying oil will be discussed in this presentation. This study aimed to utilize vegetable oils such as soybean oil for frying, of which the United States is the world’s largest producer. To overcome the vulnerability of soybean oil to oxidation due t...

  13. Protective effects of agmatine on lipopolysaccharide-injured microglia and inducible nitric oxide synthase activity.

    Science.gov (United States)

    Ahn, Soo Kyung; Hong, Samin; Park, Yu Mi; Choi, Ja Yong; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

    2012-12-17

    Proinflammatory factors released from activated microglia contribute to maintaining homeostasis against various noxious stimuli in the central nervous system. If excessive, however, they may initiate a pathologic neuroinflammatory process. In this investigation, we evaluated whether agmatine, a primary polyamine known to protect neurons, reduces lipopolysaccharide (LPS)-induced damage to microglia in vitro and in vivo. For in vitro study, BV2-immortalized murine microglia were exposed to LPS with agmatine treatment. After 24hours, cell viability and the amount of nitrite generated were determined. For in vivo study, LPS was microinjected into the corpus callosum of adult male albino mice. Agmatine was intraperitoneally administered at the time of injury. Brains were evaluated 24hours after LPS microinjection to check for immunoreactivity with a microglial marker of ionized calcium binding adaptor molecule 1 (Iba1) and inducible nitric oxide synthase (iNOS). Using western blot analysis, protein expression of iNOS as well as that of the proinflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β, was determined. Agmatine significantly reduced the LPS-induced BV2 microglial cytotoxicity from over 80% to less than 60% (pAgmatine also decreased the activities of microglia and iNOS induced by LPS microinjection into corpus callosum. Our findings reveal that agmatine attenuates LPS-induced microglial damage and suggest that agmatine may serve as a novel therapeutic strategy for neuroinflammatory diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. SERPINA3K plays antioxidant roles in cultured pterygial epithelial cells through regulating ROS system.

    Directory of Open Access Journals (Sweden)

    Chengpeng Zhu

    Full Text Available We recently demonstrated that SERPINA3K, a serine proteinase inhibitor, has antioxidant activity in the cornea. Here we investigated the antioxidant effects of SERPINA3K on the pterygial, which is partially caused by oxidative stress in pathogenesis. The head part of primary pterygial tissue was dissected and then cultured in keratinocyte serum-free defined medium (KSFM. The cultured pterygial epithelial cells (PECs were treated with SERPINA3K. The cell proliferation and migration of PECs were measured and analyzed. Western blot and quantitative real-time polymerase chain reaction (PCR assay were performed. It showed that SERPINA3K significantly suppressed the cell proliferation of PECs in a concentration-dependent manner, compared with cultured human conjunctival epithelial cells. SERPINA3K also inhibited the cell migration of PECs. Towards its underlying mechanism, SERPINA3K had antioxidant activities on the PECs by significantly inhibiting NADPH oxidase 4 (NOX4, which is an important enzyme of ROS generation, and by elevating the levels of key antioxidant factors of ROS: such as NAD(PH dehydrogenase (quinone 1 (NQO1, NF-E2-related factor-2 (NRF2 and superoxide dismutases (SOD2. Meanwhile, SERPINA3K down-regulated the key effectors of Wnt signaling pathway: β-catenin, nonphospho-β-catenin, and low-density lipoprotein receptor-related protein 6 (LRP6. We provided novel evidence that SERPINA3K had inhibitory effects on pterygium and SERPINA3K played antioxidant role via regulating the ROS system and antioxidants.

  15. Effect of Whole-Body Cryotherapy on Antioxidant Systems in Experimental Rat Model

    Directory of Open Access Journals (Sweden)

    Bronisława Skrzep-Poloczek

    2017-01-01

    Full Text Available Background. The purpose of this study was to verify the effect of whole-body cryotherapy (WBC in rats on their antioxidant systems, lipid peroxidation products, and their total oxidative status at different exposure times and temperatures. Methods. Antioxidants in serum, plasma, liver, and erythrocytes were evaluated in two study groups following 1 min of exposure to −60°C and −90°C, for 5 and 10 consecutive days. Results. WBC increased the activity of superoxide dismutase, catalase in the group subjected to 5 and 10 days exposure, −60°C. The glutathione S-transferase activity increased in the groups subjected to 10 days WBC sessions. Total antioxidant capacity increased after 5 and 10 days of 1 min WBC, −60°C; a decrease was observed at −90°C. A decreased level of erythrocyte malondialdehyde concentration was observed at −60°C after 5 and 10 days of cryostimulation. An increased concentration was measured at −90°C after 10 days, and increase of erythrocyte malondialdehyde concentration after 5 days, −90°C. Conclusions. To the best of our knowledge, this is the first research showing the effect of WBC in rats at different exposure times and temperatures. The effect of cryotherapy on enzymatic and nonenzymatic antioxidant systems was observed in the serum of animals exposed to a temperature of −60°C in comparison to control.

  16. Trichoderma harzianum T-78 supplementation of compost stimulates the antioxidant defence system in melon plants.

    Science.gov (United States)

    Bernal-Vicente, Agustina; Pascual, José A; Tittarelli, Fabio; Hernández, José A; Diaz-Vivancos, Pedro

    2015-08-30

    Compost is emerging as an alternative plant growing medium in efforts to achieve more sustainable agriculture. The addition of specific microorganisms such as Trichoderma harzianum to plant growth substrates increases yields and reduces plant diseases, but the mechanisms of such biostimulants and the biocontrol effects are not yet fully understood. In this work we investigated how the addition of citrus and vineyard composts, either alone or in combination with T. harzianum T-78, affects the antioxidant defence system in melon plants under nursery conditions. Compost application and/or Trichoderma inoculation modulated the antioxidant defence system in melon plants. The combination of citrus compost and Trichoderma showed a biostimulant effect that correlated with an increase in ascorbate recycling enzymes (monodehydroascorbate reductase, dehydroascorbate reductase) and peroxidase. Moreover, the inoculation of both composts with Trichoderma increased the activity of antioxidant enzymes, especially those involved in ascorbate recycling. Based on the long-established relationship between ascorbic acid and plant defence responses as well as plant growth and development, it can be suggested that ascorbate recycling activities play a major role in the protection provided by Trichoderma and its biostimulant effect and that these outcomes are linked to increases in antioxidant enzymes. We can conclude that the combination of citrus compost and T. harzianum T-78 constitutes a viable, environmentally friendly strategy for improving melon plant production. © 2014 Society of Chemical Industry.

  17. Antioxidant system of erythrocytes after γ-irradiation against the background of preliminary long-term overheating

    International Nuclear Information System (INIS)

    Melikhov, O.G.; Kozlov, N.B.

    1991-01-01

    A study was made of the influence of preliminary long-term heating on the state of the antioxidant system of erythrocytes after γ-irradiation. The activity of antioxidant protection enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in erythrocytes varied in different directions depending on the preliminary long-term overheating schedule and perhaps on the structure and intracellular localization of the enzyme

  18. Characterization and antioxidant activity of bovine serum albumin and sulforaphane complex in different solvent systems

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Xueyan; Zhou, Rui; Jing, Hao, E-mail: h200521@cau.edu.cn

    2014-02-15

    Modes and influencing factors of bovine serum albumin (BSA) and sulforaphane (SFN) interaction will help us understand the interaction mechanisms and functional changes of bioactive small molecule and biomacromolecule. This study investigated interaction mechanisms of BSA and SFN and associated antioxidant activity in three solvent systems of deionized water (dH{sub 2}O), dimethyl sulfoxide (DMSO) and ethanol (EtOH), using Fourier transform infrared spectroscopy (FT-IR), fluorescence spectroscopy, synchronous fluorescence spectroscopy, DPPH and ABTS radical scavenging assays. The results revealed that SFN had ability to quench BSA's fluorescence in static modes, and to interact with BSA at both tyrosine (Tyr) and tryptophan (Trp) residues, while the Trp residues were highly sensitive, which was demonstrated by fluorescence at 340 nm. Hydrophobic forces, hydrogen bonds and van der Waals interactions were all involved in BSA and SFN interaction, which were not significantly changed by three solvents. The binding constant values and binding site numbers were in a descending order of dH{sub 2}O>DMSO>EtOH. The values of free energy change were in a descending order of dH{sub 2}O>DMSO>EtOH, which indicated that the binding forces were in a descending order of dH{sub 2}O>DMSO>EtOH. There was no significant difference in antioxidant activity between SFN and BSA–SFN. Moreover, three solvents had not significant influence on antioxidant activity of SFN and BSA–SFN. -- Highlights: • We report interaction mechanisms of BSA and sulforaphane in three solvent systems. • We report antioxidant activity of BSA–sulforaphane complex in three solvent systems. • Decreasing the solvent polarity will decrease the binding of BSA and sulforaphane. • Three solvents had not influence on antioxidant activity of BSA–sulforaphane.

  19. The subpopulation of microglia sensitive to neurotransmitters/neurohormones is modulated by stimulation with LPS, interferon-γ, and IL-4.

    Science.gov (United States)

    Pannell, Maria; Szulzewsky, Frank; Matyash, Vitali; Wolf, Susanne A; Kettenmann, Helmut

    2014-05-01

    Recently, neurotransmitters/neurohormones have been identified as factors controlling the function of microglia, the immune competent cells of the central nervous system. In this study, we compared the responsiveness of microglia to neurotransmitters/neurohormones. We freshly isolated microglia from healthy adult C57Bl/6 mice and found that only a small fraction (1-20%) responded to the application of endothelin, histamine, substance P, serotonin, galanin, somatostatin, angiotensin II, vasopressin, neurotensin, dopamine, or nicotine. In cultured microglia from neonatal and adult mice, a similarly small population of cells responded to these neurotransmitters/neurohormones. To induce a proinflammatory phenotype, we applied lipopolysaccaride (LPS) or interferon-gamma (IFN-γ) to the cultures for 24 h. Several of the responding populations increased; however, there was no uniform pattern when comparing adult with neonatal microglia or LPS with IFN-γ treatment. IL-4 as an anti-inflammatory substance increased the histamine-, substance P-, and somatostatin-sensitive populations only in microglia from adult, but not in neonatal cells. We also found that the expression of different receptors was not strongly correlated, indicating that there are many different populations of microglia with a distinct set of receptors. Our results demonstrate that microglial cells are a heterogeneous population with respect to their sensitivity to neurotransmitters/neurohormones and that they are more responsive in defined activation states. Copyright © 2014 Wiley Periodicals, Inc.

  20. Noninvasive Quantification of Retinal Microglia Using Widefield Autofluorescence Imaging.

    Science.gov (United States)

    Kokona, Despina; Schneider, Nadia; Giannakaki-Zimmermann, Helena; Jovanovic, Joel; Ebneter, Andreas; Zinkernagel, Martin

    2017-04-01

    To validate widefield autofluorescence (AF) in vivo imaging of the retina in mice expressing green fluorescent protein (gfp) in microglia, and to monitor retinal microglia reconstitution in vivo after lethal irradiation and bone marrow transplantation. Transgenic Cx3cr1gfp/gfp and wildtype Balb/c mice were used in this study. A confocal scanning laser ophthalmoscope was used for AF imaging with a 55° and a widefield 102° lens. Intrasession reproducibility was assessed for each lens. To investigate reconstitution in vivo, bone marrow from Cx3cr1gfp/gfp mice was used to rescue lethally irradiated wildtype mice. Data were compared to confocal microscopy of retinal flat mounts. Both the 55° and the 102° lens produced high resolution images of retinal microglia with similar microglia density. However, compared to the 55° lens, the widefield 102° lens captured approximately 3.6 times more microglia cells (1515 ± 123 cells versus 445 ± 76 cells [mean ± SD], for 102° and 55°, respectively, P < 0.001). No statistical difference in the number of gfp positive cells within corresponding areas was observed within the same imaging session. Imaging of microglia reconstitution showed a similar time course compared to flat mount preparations with an excellent correlation between microglia cell numbers in AF and gfp-stained flat mounts (R = 0.92, P < 0.0001). Widefield AF imaging of mice with gfp expressing microglia can be used to quantify retinal microglia. In vivo microglia counts corresponded very well with ex vivo counts on retinal flat mounts. As such, AF imaging can largely replace ex vivo quantification.

  1. Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response.

    Science.gov (United States)

    Cai, Qing; Li, Yuanyuan; Pei, Gang

    2017-03-24

    Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated. Further, GLP effect on microglial behavioural modulations in correlation with the inflammatory responses remains to be unravelled. The aim of this work was to quantitatively analyse the contributions of GLP on microglia. The BV2 microglia and primary mouse microglia were stimulated by lipopolysaccharides (LPS) and amyloid beta 42 (Aβ 42 ) oligomer, respectively. Investigation on the effect of GLP was carried by quantitative determination of the microglial pro- and anti-inflammatory cytokine expressions and behavioural modulations including migration, morphology and phagocytosis. Analysis of microglial morphology and phagocytosis modulations was confirmed in the zebrafish brain. Quantitative results revealed that GLP down-regulates LPS- or Aβ-induced pro-inflammatory cytokines and promotes anti-inflammatory cytokine expressions in BV-2 and primary microglia. In addition, GLP attenuates inflammation-related microglial migration, morphological alterations and phagocytosis probabilities. We also showed that modulations of microglial behavioural responses were associated with MCP-1 and C1q expressions. Overall, our study provides an insight into the GLP regulation of LPS- and Aβ-induced neuroinflammation and serves an implication that the neuroprotective function of GLP might be achieved through modulation of microglial inflammatory and behavioural responses.

  2. In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed.

    Science.gov (United States)

    Vainchtein, I D; Vinet, J; Brouwer, N; Brendecke, S; Biagini, G; Biber, K; Boddeke, H W G M; Eggen, B J L

    2014-10-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of microglia, the resident macrophages of the CNS, remains ambiguous. Therefore, we have compared the phenotypes of microglia and macrophages in a mouse model for MS, experimental autoimmune encephalomyelitis (EAE). In order to properly discriminate between these two cell types, microglia were defined as CD11b(pos) CD45(int) Ly-6C(neg) , and infiltrated macrophages as CD11b(pos) CD45(high) Ly-6C(pos) . During clinical EAE, microglia displayed a weakly immune-activated phenotype, based on the expression of MHCII, co-stimulatory molecules (CD80, CD86, and CD40) and proinflammatory genes [interleukin-1β (IL-1β) and tumour necrosis factor- α (TNF-α)]. In contrast, CD11b(pos) CD45(high) Ly-6C(pos) infiltrated macrophages were strongly activated and could be divided into two populations Ly-6C(int) and Ly-6C(high) , respectively. Ly-6C(high) macrophages contained less myelin than Ly-6C(int) macrophages and expression levels of the proinflammatory cytokines IL-1β and TNF-α were higher in Ly-6C(int) macrophages. Together, our data show that during clinical EAE, microglia are only weakly activated whereas infiltrated macrophages are highly immune reactive. © 2014 Wiley Periodicals, Inc.

  3. Development of an active food packaging system with antioxidant properties based on green tea extract.

    Science.gov (United States)

    Carrizo, Daniel; Gullo, Giuseppe; Bosetti, Osvaldo; Nerín, Cristina

    2014-01-01

    A formula including green tea extract (GTE) was developed as an active food packaging material. This formula was moulded to obtain an independent component/device with antioxidant properties that could be easily coupled to industrial degassing valves for food packaging in special cases. GTE components (i.e., gallic acid, catechins and caffeine) were identified and quantified by HPLC-UV and UPLC-MS and migration/diffusion studies were carried out. Antioxidant properties of the formula alone and formula-valve were measured with static and dynamic methods. The results showed that the antioxidant capacity (scavenging of free radicals) of the new GTE formula was 40% higher than the non-active system (blank). This antioxidant activity increased in parallel with the GTE concentration. The functional properties of the industrial target valve (e.g., flexibility) were studied for different mixtures of GTE, and good results were found with 17% (w/w) of GTE. This new active formula can be an important addition for active packaging applications in the food packaging industry, with oxidative species-scavenging capacity, thus improving the safety and quality for the consumer and extending the shelf-life of the packaged food.

  4. Influence Of Pentoxifylline And Mexidol On Lipid Peroxidation And Anti-oxidant System In Patients With Urolithiasis

    Directory of Open Access Journals (Sweden)

    A.B. Polozov

    2009-12-01

    Full Text Available Research objective is to prove correction possibility of lipid peroxidation and antioxidant system protection in neph-rolithiasis by taking pentoxifylline and mexidol. 158 patients with kidney concretion have been under the research. Distance shock-wave lithotripsy (ESWL has been carried out. Structure of stones and antioxidant system state have been investigated in all patients. They have been divided into three groups - control, receiving pentoxifylline and receiving mexidol. Influence of indicated preparations on processes of lipid peroxidation and antioxidant system has been studied in case of different structure of concretion

  5. Whole body exposure to low-dose γ-radiation enhances the antioxidant defense system

    International Nuclear Information System (INIS)

    Pathak, C.M.; Avti, P.K.; Khanduja, K.L.; Sharma, S.C.

    2008-01-01

    It is believed that the extent of cellular damage by low- radiation dose is proportional to the effects observed at high radiation dose as per the Linear-No-Threshold (LNT) hypothesis. However, this notion may not be true at low-dose radiation exposure in the living system. Recent evidence suggest that the living organisms do not respond to ionizing radiations in a linear manner in the low dose range 0.01-0.5Gy and rather restore the homeostasis both in vivo and in vitro by normal physiological mechanisms such as cellular and DNA repair processes, immune reactions, antioxidant defense, adaptive responses, activation of immune functions, stimulation of growth etc. In this study, we have attempted to find the critical radiation dose range and the post irradiation period during which the antioxidant defense systems in the lungs, liver and kidneys remain stimulated in these organs after whole body exposure of the animals to low-dose radiation

  6. [The activity of glutathione antioxidant system at melaksen and valdoxan action under experimental hyperthyroidism in rats].

    Science.gov (United States)

    Gorbenko, M V; Popova, T N; Shul'gin, K K; Popov, S S

    2013-01-01

    Investigation of glutathione antioxidant system activity and diene conjugates content in rats liver and blood serum at the influence of melaksen and valdoxan under experimental hyperthyroidism (EG) has been revealed. It has been established that the activities of glutathione reductase (GR), glutathione peroxidase (GP) and glutathione transferase (GT), growing at pathological conditions, change to the side of control value at these substunces introduction. Reduced glutathione content (GSH) at melaxen and valdoxan action increased compared with values under the pathology, that, obviously, could be associated with a reduction of its spending on the detoxication of free radical oxidation (FRO) toxic products. Diene conjugates level in rats liver and blood serum, increasing at experimental hyperthyroidism conditions, under introduction of melatonin level correcting drugs, also approached to the control meaning. Results of the study indicate on positive effect of melaxen and valdoxan on free radical homeostasis, that appears to be accompanied by decrease of load on the glutathione antioxidant system in comparison with the pathology.

  7. Microglia are required for astroglial toll-like receptor 4 response and for optimal TLR2 and TLR3 response

    DEFF Research Database (Denmark)

    Holm, Thomas H; Draeby, Dina; Owens, Trevor

    2012-01-01

    Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll-like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond as stron......Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll-like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond...... astrocytes from mixed glial cultures and measured their response to TLR agonists. Our results show that the response of astrocytes to TLR2 and TLR3 agonists is greatly enhanced by, and response to TLR4 agonists is completely dependent on, the presence of functional microglia. In the case of the TLR4 response...

  8. Regulation of vacuolar H+-ATPase in microglia by RANKL

    International Nuclear Information System (INIS)

    Serrano, Eric M.; Ricofort, Ryan D.; Zuo, Jian; Ochotny, Noelle; Manolson, Morris F.; Holliday, L. Shannon

    2009-01-01

    Vacuolar H + -ATPases (V-ATPases) are large electrogenic proton pumps composed of numerous subunits that play vital housekeeping roles in the acidification of compartments of the endocytic pathway. Additionally, V-ATPases play specialized roles in certain cell types, a capacity that is linked to cell type selective expression of isoforms of some of the subunits. We detected low levels of the a3 isoform of the a-subunit in mouse brain extracts. Examination of various brain-derived cell types by immunoblotting showed a3 was expressed in the N9 microglia cell line and in primary microglia, but not in other cell types. The expression of a3 in osteoclasts requires stimulation by Receptor Activator of Nuclear Factor κB-ligand (RANKL). We found that Receptor Activator of Nuclear Factor κB (RANK) was expressed by microglia. Stimulation of microglia with RANKL triggered increased expression of a3. V-ATPases in microglia were shown to bind microfilaments, and stimulation with RANKL increased the proportion of V-ATPase associated with the detergent-insoluble cytoskeletal fraction and with actin. In summary, microglia express the a3-subunit of V-ATPase. The expression of a3 and the interaction between V-ATPases and microfilaments was modulated by RANKL. These data suggest a novel molecular pathway for regulating microglia.

  9. Activation of Microglia by Histamine and Substance P

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    Jin Zhu

    2014-08-01

    Full Text Available Background: Activated microglia perform many of the immune effector functions typically associated with macrophages. However, the regulators involved in microglial activation are not well defined. Because microglia play a pivotal role in immune surveillance of the CNS, we studied the effect of the neuromediators histamine and substance P on microglia. Methods: The induction of microglial activation by histamine and substance P was examined using primary cultured microglia. Fluorescent images were acquired with a confocal microscope. The levels of TNF-α and IL-6 were measured with a commercial ELISA kit. Intracellular reactive oxygen species (ROS levels were determined by dichlorodihydrofluorescein oxidation. The mitochondrial membrane potential was assessed with the MitoProbe™ JC-1 assay kit. Results: We found that the neuromediators histamine and substance P were able to stimulate microglial activation and the subsequent production of ROS and proinflammatory factors TNF-α and IL-6. These effects were partially abolished by antagonists of the histamine receptors H1 and H4 and of the substance P receptors NK-1, NK-2 and NK-3. Histamine induced mitochondrial membrane depolarization in microglia. Conclusions: These results indicate that the neuromediators histamine and SP can trigger microglial activation and release of pro-inflammatory factors from microglia, thus contributing to the development of microglia-mediated inflammation in the brain.

  10. Anti-inflammatory effects of glaucocalyxin B in microglia cells

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    Ping Gan

    2015-05-01

    Full Text Available Over-activated microglia is involved in various kinds of neurodegenerative process including Parkinson, Alzheimer and HIV dementia. Suppression of microglial over activation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory and neuroprotective effects of the ent-kauranoid diterpenoids, which were isolated from the aerial parts of Rabdosia japonica (Burm. f. var. glaucocalyx (Maxim. Hara, were investigated in cultured microglia cells. Glaucocalyxin B (GLB, one of five ent-kauranoid diterpenoids, significantly decreased the generation of nitric oxide (NO, tumor necrosis factor (TNF-α, interleukin (IL-1β, cyclooxygenase (COX-2 and inducible nitric oxide synthase (iNOS in the lipopolysaccharide (LPS-activated microglia cells. In addition, GLB inhibited activation of nuclear factor-κB (NF-κB, p38 mitogen-activated protein kinase (MAPK and generation of reactive oxygen species (ROS in LPS-activated microglia cells. Furthermore, GLB strongly induced the expression of heme oxygenase (HO-1 in BV-2 microglia cells. Finally, GLB exhibited neuroprotective effect by preventing over-activated microglia induced neurotoxicity in a microglia/neuron co-culture model. Taken together, the present study demonstrated that the GLB possesses anti-nueroinflammatory activity, and might serve as a potential therapeutic agent for treating neuroinflammatory diseases.

  11. Immune priming of microglia in a DNA repair deficient model of accelerated aging

    NARCIS (Netherlands)

    Raj, D. A.; Jaarsma, D.; Brouwer, N.; Hoeijmakers, J. H. J.; Eggen, B. J. L.; Biber, K. P. H.; Boddeke, H. W. G. M.

    2012-01-01

    Ageing of brain tissue has been associated with enhanced activity and immune priming of microglia in mice, rats and primates. It is, however, not clear yet whether this age-related microglia activation is due to the intrinsic process of microglia aging or is an adapted response of microglia to the

  12. Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains.

    Science.gov (United States)

    Abreu, Renata Viana; Silva-Oliveira, Eliane Moretto; Moraes, Márcio Flávio Dutra; Pereira, Grace Schenatto; Moraes-Santos, Tasso

    2011-10-01

    Coffee is a popular beverage consumed worldwide and its effect on health protection has been well studied throughout literature. This study investigates the effect of chronic coffee and caffeine ingestion on cognitive behavior and the antioxidant system of rat brains. The paradigms of open field and object recognition were used to assess locomotor and exploratory activities, as well as learning and memory. The antioxidant system was evaluated by determining the activities of glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as the lipid peroxidation and reduced glutathione content. Five groups of male rats were fed for approximately 80 days with different diets: control diet (CD), fed a control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and 0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented with caffeine. The estimated caffeine intake was approximately 20 and 40 mg/kg per day, for the 3%Co-0.04%Ca and 6%Co-0.08%Ca treatments, respectively. At 90 days of life, the animals were subjected to the behavioral tasks and then sacrificed. The results indicated that the intake of coffee, similar to caffeine, improved long-term memory when tested with object recognition; however, this was not accompanied by an increase in locomotor and exploratory activities. In addition, chronic coffee and caffeine ingestion reduced the lipid peroxidation of brain membranes and increased the concentration of reduced-glutathione. The activities of the GR and SOD were similarly increased, but no change in GPx activity could be observed. Thus, besides improving cognitive function, our data show that chronic coffee consumption modulates the endogenous antioxidant system in the brain. Therefore, chronic coffee ingestion, through the protection of the antioxidant system, may play an important role in preventing age-associated decline in the cognitive

  13. The ischemic environment drives microglia and macrophage function

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    Stefano eFumagalli

    2015-04-01

    Full Text Available Cells of myeloid origin such as microglia and macrophages act at the crossroads of several inflammatory mechanisms during pathophysiology. Besides pro-inflammatory activity (M1 polarization, myeloid cells acquire protective functions (M2 and participate in the neuroprotective innate mechanisms after brain injury. Experimental research is making considerable efforts to understand the rules that regulate the balance between toxic and protective brain innate immunity. Environmental changes affects microglia/macrophage functions. Hypoxia can affect myeloid cell distribution, activity and phenotype. With their intrinsic differences, microglia and macrophages respond differently to hypoxia, the former depending on ATP to activate, the latter switching to anaerobic metabolism and adapting to hypoxia. Myeloid cell functions include homeostasis control, damage-sensing activity, chemotaxis and phagocytosis, all distinctive features of these cells. Specific markers and morphologies enable to recognize each functional state. To ensure homeostasis and activate when needed, microglia/macrophage physiology is finely tuned. Microglia are controlled by several neuron-derived components, including contact-dependent inhibitory signals and soluble molecules. Changes in this control can cause chronic activation or priming with specific functional consequences. Strategies such as stem cell treatment may enhance microglia protective polarization. This review presents data from the literature that has greatly advanced our understanding of myeloid cell action in brain injury. We discuss the selective responses of microglia and macrophages to hypoxia after stroke and review relevant markers with the aim of defining the different subpopulations of myeloid cells that are recruited to the injured site. We also cover the functional consequences of chronically active microglia and review pivotal works on microglia regulation that offer new therapeutic possibilities for acute

  14. P2X7 signaling promotes microsphere embolism-triggered microglia activation by maintaining elevation of Fas ligand

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    Lu Ying-mei

    2012-07-01

    Full Text Available Abstract Background The cerebral microvascular occlusion elicits microvascular injury which mimics the different degrees of stroke severity observed in patients, but the mechanisms underlying these embolic injuries are far from understood. The Fas ligand (FasL-Fas system has been implicated in a number of pathogenic states. Here, we examined the contribution of microglia-derived FasL to brain inflammatory injury, with a focus on the potential to suppress the FasL increase by inhibition of the P2X7-FasL signaling with pharmacological or genetic approaches during ischemia. Methods The cerebral microvascular occlusion was induced by microsphere injection in experimental animals. Morphological changes in microglial cells were studied immunohistochemically. The biochemical analyses were used to examine the intracellular changes of P2X7/FasL signaling. The BV-2 cells and primary microglia from mice genetically deficient in P2X7 were used to further establish a linkage between microglia activation and FasL overproduction. Results The FasL expression was continuously elevated and was spatiotemporally related to microglia activation following microsphere embolism. Notably, P2X7 expression concomitantly increased in microglia and presented a distribution pattern that was similar to that of FasL in ED1-positive cells at pathological process of microsphere embolism. Interestingly, FasL generation in cultured microglia cells subjected to oxygen-glucose deprivation-treated neuron-conditioned medium was prevented by the silencing of P2X7. Furthermore, FasL induced the migration of BV-2 microglia, whereas the neutralization of FasL with a blocking antibody was highly effective in inhibiting ischemia-induced microglial mobility. Similar results were observed in primary microglia from wild-type mice or mice genetically deficient in P2X7. Finally, the degrees of FasL overproduction and neuronal death were consistently reduced in P2X7−/− mice compared with wild

  15. A study of Some Hormones and AntioxidantSystems Disturbances in Older Men

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    Reem Abdul-Raheem Al-Saadi

    2018-02-01

    Full Text Available      Ageing is a physiological phenomenon that manifested itself with disturbances of many homeostatic regulating mechanisms of the body . The present study was conducted and employed to investigate two major systems( hormones and antioxidant systems that can be implicated in progress of aging .The total number of subjects included in the present study was fifty (50 healthy men and classified according to their ages into two groups, the first group included 25 younger men (control group and their ages ranged between 21 to 30 years old whereas the second group included 25 older men and their ages were between 61 to 70 years old.  Data obtained from this study indicated a significant decrease(p0.05 occurring among hormones( testosterone  , T3 and glutathione peroxidase and of malondehyde .   From these results ,one can be concluded that with ageing there are many disturbances and fluctuations of hypothalamic-adrenal and thyroid axis that accompanied with drop of essential antioxidant components that may be lead to suppress of defense against free radicals and the present study concluded that the changes occurring in studied hormones have not relations and effects on the antioxidant systems.

  16. Dystrophic microglia in the aging human brain.

    Science.gov (United States)

    Streit, Wolfgang J; Sammons, Nicole W; Kuhns, Amanda J; Sparks, D Larry

    2004-01-15

    We have studied microglial morphology in the human cerebral cortex of two nondemented subjects using high-resolution LN-3 immunohistochemistry. Several abnormalities in microglial cytoplasmic structure, including deramification, spheroid formation, gnarling, and fragmentation of processes, were identified. These changes were determined to be different from the morphological changes that occur during microglial activation and they were designated collectively as microglial dystrophy. Quantitative evaluation of dystrophic changes in microglia revealed that these were much more prevalent in the older subject (68-year-old) than in the younger one (38-year-old). Thus, we conclude that microglial dystrophy is a sign of microglial cell senescence. We hypothesize that microglial senescence could be important for understanding age-related declines in cognitive function. Copyright 2003 Wiley-Liss, Inc.

  17. 6-Mercaptopurine attenuates tumor necrosis factor-? production in microglia through Nur77-mediated transrepression and PI3K/Akt/mTOR signaling-mediated translational regulation

    OpenAIRE

    Huang, Hsin-Yi; Chang, Hui-Fen; Tsai, Ming-Jen; Chen, Jhih-Si; Wang, Mei-Jen

    2016-01-01

    Background The pathogenesis of several neurodegenerative diseases often involves the microglial activation and associated inflammatory processes. Activated microglia release pro-inflammatory factors that may be neurotoxic. 6-Mercaptopurine (6-MP) is a well-established immunosuppressive drug. Common understanding of their immunosuppressive properties is largely limited to peripheral immune cells. However, the effect of 6-MP in the central nervous system, especially in microglia in the context ...

  18. COMBINED EFFECTS OF CO2 AND O3 ON ANTIOXIDATIVE AND PHOTOPROTECTIVE DEFENSE SYSTEMS IN NEEDLES OF PONDEROSA PINE

    Science.gov (United States)

    To determine interactive effects of important environmental stresses on biochemical defense mechanisms of tree seedlings, we studied responses to elevated O3 and elevated atmospheric CO2 on antioxidative and photoprotective systems in needles of ponderosa pine (Pinus ponderosa Do...

  19. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.

    Science.gov (United States)

    McMillin, Matthew; Frampton, Gabriel; Thompson, Michelle; Galindo, Cheryl; Standeford, Holly; Whittington, Eric; Alpini, Gianfranco; DeMorrow, Sharon

    2014-07-10

    Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. These findings suggest that CCL2 is elevated systemically following acute liver injury and that CCL2 is involved in both the

  20. Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems

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    Sung Ryul Lee

    2018-01-01

    Full Text Available Zinc is recognized as an essential trace metal required for human health; its deficiency is strongly associated with neuronal and immune system defects. Although zinc is a redox-inert metal, it functions as an antioxidant through the catalytic action of copper/zinc-superoxide dismutase, stabilization of membrane structure, protection of the protein sulfhydryl groups, and upregulation of the expression of metallothionein, which possesses a metal-binding capacity and also exhibits antioxidant functions. In addition, zinc suppresses anti-inflammatory responses that would otherwise augment oxidative stress. The actions of zinc are not straightforward owing to its numerous roles in biological systems. It has been shown that zinc deficiency and zinc excess cause cellular oxidative stress. To gain insights into the dual action of zinc, as either an antioxidant or a prooxidant, and the conditions under which each role is performed, the oxidative stresses that occur in zinc deficiency and zinc overload in conjunction with the intracellular regulation of free zinc are summarized. Additionally, the regulatory role of zinc in mitochondrial homeostasis and its impact on oxidative stress are briefly addressed.

  1. Determination of antioxidant activity of Hibiscus sabdariffa and Croton caudatus in Saccharomyces cerevisiae model system.

    Science.gov (United States)

    Subhaswaraj, Pattnaik; Sowmya, M; Bhavana, V; Dyavaiah, Madhu; Siddhardha, Busi

    2017-08-01

    From ancient times, plants and plant derived products are exploited as a prominent source of folkloric medicines with tremendous therapeutic potential for an array of health disorders. In the present study, ethanolic leaf extract of Hibiscus sabdariffa and Croton caudatus were evaluated for free radical scavenging activity in Saccharomyces cerevisiae model system. H. sabdariffa and C. caudatus showed tremendous DPPH free radical scavenging potential with an IC 50 value of 184.88 and 305.39 µg/mL respectively at a concentration of 500 µg/mL. The ethanolic leaf extract of H. sabdariffa and C. caudatus also showed significant hydoxyl radical scavenging and total antioxidant activity. Ascorbic acid was used as positive control. The in vitro antioxidant activity was further supported by in vivo studies using radical scavenging mechanism in S. cerevisiae wild type and its isogenic deletion strains sod1∆ and tsa1∆ . The mutant yeast cells substantially scavenged the stress generated by H 2 O 2 when supplemented with ethanolic leaf extract of H. sabdariffa and C. caudatus as evident from spot assays followed by fluorescence assay (DCF-DA) using fluorescence microscopic and intensity studies. H. sabdariffa and C.caudatus significantly neutralize the ROS level in yeast mutants with concomitant decrease in fluorescence intensity as compared to the untreated yeast cells. The results suggested the efficacy of H. sabdariffa and C. caudatus as potent antioxidants in yeast system and thus their futuristic applications in therapeutics.

  2. Self-Assembly of Multi-nanozymes to Mimic an Intracellular Antioxidant Defense System.

    Science.gov (United States)

    Huang, Yanyan; Liu, Zhen; Liu, Chaoqun; Ju, Enguo; Zhang, Yan; Ren, Jinsong; Qu, Xiaogang

    2016-06-01

    In this work, for the first time, we constructed a novel multi-nanozymes cooperative platform to mimic intracellular antioxidant enzyme-based defense system. V2 O5 nanowire served as a glutathione peroxidase (GPx) mimic while MnO2 nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V2 O5 @pDA@MnO2 nanocomposite could serve as one multi-nanozyme model to mimic intracellular antioxidant enzyme-based defense procedure in which, for example SOD, CAT, and GPx co-participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Comparison of microglia and infiltrating CD11c+ cells as antigen presenting cells for T cell proliferation and cytokine response

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Løbner, Morten; Cédile, Oriane

    2014-01-01

    BACKGROUND: Tissue-resident antigen-presenting cells (APC) exert a major influence on the local immune environment. Microglia are resident myeloid cells in the central nervous system (CNS), deriving from early post-embryonic precursors, distinct from adult hematopoietic lineages. Dendritic cells...... (DC) and macrophages infiltrate the CNS during experimental autoimmune encephalomyelitis (EAE). Microglia are not considered to be as effective APC as DC or macrophages. METHODS: In this work we compared the antigen presenting capacity of CD11c+ and CD11c- microglia subsets with infiltrating CD11c......+ APC, which include DC. The microglial subpopulations (CD11c- CD45dim CD11b+ and CD11c+ CD45dim CD11b+) as well as infiltrating CD11c+ CD45high cells were sorted from CNS of C57BL/6 mice with EAE. Sorted cells were characterised by flow cytometry for surface phenotype and by quantitative real-time PCR...

  4. Prevention of lipid oxidation in omega-3 enriched oofds by antioxidants and the use of delivery systems

    DEFF Research Database (Denmark)

    Jacobsen, Charlotte

    Due to the health beneficial effects of marine omega-3 fatty acids there is an increasing interest in developing functional foods containing these healthy fatty acids. However, such foods are very susceptible to lipid oxidation, which will give rise to undesirable off-flavours and unhealthy...... oxidation products. Efficients strategies to prevent lipid oxidation are therefore required. Such strategies include addition of antioxidants or the use of omega-3 delivery emulsions. However, antioxidant efficacy in complex omega-3 enriched foods are influenced by many factors including the lipophilicity...... of the antioxidants. Selection of the optimal antioxidant system is therefore a major challenge. Likewise, a range of factors can influence the ability of omega-3 delivery systems to protect the omega-3 fatty acids against oxidation after addition to food systems. These challenges will be discussed...

  5. Influence of drugs with antioxidant properties on the state of the sperm antioxidant system in men with excretory-toxic forms of infertility

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    O.K. Onufrovych

    2013-10-01

    Full Text Available Since the development of many disorders of the reproductive function in men involves processes of free radical oxidation, the purpose of this study was to form an evaluation of the pro- and antioxidant status of sperm and to restore its biological usefulness in men with excretory-toxic forms of infertility by using drugs with antioxidant properties. It is shown that excretory-toxic forms of infertility in men are mostly caused by such infectious agents as Chlamydia (22%, Chlamydia + Ureaplasma (16%, Chlamydia + Trichomonas (13%, Ureaplasma (10%. This reduces the total number of sperm in the ejaculate by 2.7 times, and motility by 1.8 times. The number of abnormal forms increases by 1.75 times. With the development of chronic inflammation of the male sex organs sperm lipid peroxidation increases by 1.3 times while the activity of glutathione peroxidase decreases (by 2.3 times and that of glutathione reductase (by 1.7 times. We observed a close correlation between the low biological quality of sperm (low concentration, low number and motility of sperm in the ejaculate with activation of lipid peroxidation and inhibition of activity of the glutathione antioxidant system. In the case of superoxide dismutase, the negative impact of reactive oxygen species on this enzyme was not observed. A course of drugs with antioxidant properties – vitamin E, vitamin C and zinc sulfate leads to improvement in the indicators on the spermagram (mostly sperm mobility and morphology, to reduction of the number of peroxide compounds and activation of the glutathione antioxidant system. In this case, the activity of glutathione peroxidase is increased by 1.5 times and the activity of glutathione reductase by 1.3 times. The activity of superoxide dismutase at the same time approaches the norm for zoospermia. The data obtained show that one of the pathogenic factors of the chronic inflammation of male sex organs, considered as a main developmental reason for infertility

  6. Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation

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    Dora eBrites

    2015-12-01

    Full Text Available Patients with chronic inflammation are often associated with the emergence of depression symptoms, while diagnosed depressed patients show increased levels of circulating cytokines. Further studies revealed the activation of the brain immune cell microglia in depressed patients with a greater magnitude in individuals that committed suicide, indicating a crucial role for neuroinflammation in depression brain pathogenesis. Rapid advances in the understanding of microglial and astrocytic neurobiology were obtained in the past fifteen to twenty years. Indeed, recent data reveal that microglia play an important role in managing neuronal cell death, neurogenesis, and synaptic interactions, besides their involvement in immune-response generating cytokines. The communication between microglia and neurons is essential to synchronize these diverse functions with brain activity. Evidence is accumulating that secreted extracellular vesicles (EVs, comprising ectosomes and exosomes with a size ranging from 0.1 to 1 μm, are key players in intercellular signaling. These EVs may carry specific proteins, mRNAs and microRNAs (miRNAs. Transfer of exosomes to neurons was shown to be mediated by oligodendrocytes, microglia and astrocytes that may either be supportive to neurons, or instead disseminate the disease. Interestingly, several recent reports have identified changes in miRNAs in depressed patients, which target not only crucial pathways associated with synaptic plasticity, learning and memory but also the production of neurotrophic factors and immune cell modulation. In this article, we discuss the role of neuroinflammation in the emergence of depression, namely dynamic alterations in the status of microglia response to stimulation, and how their activation phenotypes may have an etiological role in neurodegeneneration, in particular in depressive-like behavior. We will overview the involvement of miRNAs, exosomes, ectosomes and microglia in regulating

  7. Antioxidant effect of seaweed extracts in food emulsion systems enriched with fish oil

    DEFF Research Database (Denmark)

    Larsen, Ditte Baun; Farvin, Sabeena; Jacobsen, Charlotte

    Natural antioxidants derived from marine algae have a high content of bioactive components with potential for improving oxidative stability of lipids in food systems. In this presentation we will discuss results from our ongoing work on the brown algae Fucus vesiculosus. This seaweed contains...... such as phlorotannins, a dominant polyphenolic compound. However, studies on the effectiveness of seaweed extracts in food model systems are sparse, therefore there is a need to look further into this area. Results obtained in our lab with different extracts of F. Vesiculosus in a range of different food models...

  8. Simulating of Top-Cross system for enhancement of antioxidants in maize grain

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    Jelena Vancetovic

    2014-04-01

    Full Text Available Blue maize (Zea mays L. is grown for its high content of antioxidants. Conversion of yellow and white to blue maize is time consuming because several genes affect blue color. After each backcross selfing is needed for color to be expressed. In order to overcome the problem of time and effort needed for conversion to blue kernel color, we have set a pilot experiment simulating a Top-cross system for increasing antioxidants in maize grain. The idea is to alternately sow six rows of sterile standard quality hybrid and two rows of blue maize in commercial production. Five commercial ZP hybrids were crossed with a blue pop-corn population. Xenia effect caused by cross-pollination produced blue grain on all hybrids in the same year. Chemical analyses of the grains of five selfed original hybrids, five cross-pollinated hybrids and selfed blue popcorn pollinator were performed. Cross-fertilization with blue popcorn had different impact on antioxidant capacity and phytonutrients, increasing them significantly in some but not all cross-pollinated hybrids. Popcorn blue pollinator had higher values for all the analyzed traits than either selfed or cross-pollinated hybrids. Selfed vs. pollinated hybrids showed significant difference for total antioxidant capacity (p<0.1, total phenolics and total yellow pigments (p<0.01, with the increase of total phenolics and decrease of total yellow pigments in pollinated ones. Total flavonoids showed a little non-significant decrease in pollinated hybrids, while total anthocyanins were not detected in selfed yellow hybrids. Blue maize obtained this way has shown good potential for growing high quality phytonutrient genotypes.

  9. FimH adhesin of Escherichia coli K1 type 1 fimbriae activates BV-2 microglia

    International Nuclear Information System (INIS)

    Lee, Jongseok; Shin, Sooan; Teng, C.-H.; Hong, Suk Jin; Kim, Kwang Sik

    2005-01-01

    The generation of intense inflammation in the subarachnoid space in response to meningitis-causing bacteria contributes to brain dysfunction and neuronal injury in bacterial meningitis. Microglia, the major immune effector cells in the central nervous system (CNS), become activated by bacterial components to produce proinflammatory immune mediators. In this study, we showed that FimH adhesin, a tip component of type 1 fimbriae of meningitis-causing Escherichia coli K1, activated the murine microglial cell line, BV-2, which resulted in the production of nitric oxide and the release of tumor necrosis factor-α. Mitogen-activated protein kinases, ERK and p-38, and nuclear factor-κB were involved in FimH adhesin-mediated microglial activation. These findings suggest that FimH adhesin contributes to the CNS inflammatory response by virtue of activating microglia in E. coli meningitis

  10. Microglia and Aging: The Role of the TREM2–DAP12 and CX3CL1-CX3CR1 Axes

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    Carmen Mecca

    2018-01-01

    Full Text Available Depending on the species, microglial cells represent 5–20% of glial cells in the adult brain. As the innate immune effector of the brain, microglia are involved in several functions: regulation of inflammation, synaptic connectivity, programmed cell death, wiring and circuitry formation, phagocytosis of cell debris, and synaptic pruning and sculpting of postnatal neural circuits. Moreover, microglia contribute to some neurodevelopmental disorders such as Nasu-Hakola disease (NHD, and to aged-associated neurodegenerative diseases, such as Alzheimer’s disease (AD, Parkinson’s disease (PD, and others. There is evidence that human and rodent microglia may become senescent. This event determines alterations in the microglia activation status, associated with a chronic inflammation phenotype and with the loss of neuroprotective functions that lead to a greater susceptibility to the neurodegenerative diseases of aging. In the central nervous system (CNS, Triggering Receptor Expressed on Myeloid Cells 2-DNAX activation protein 12 (TREM2-DAP12 is a signaling complex expressed exclusively in microglia. As a microglial surface receptor, TREM2 interacts with DAP12 to initiate signal transduction pathways that promote microglial cell activation, phagocytosis, and microglial cell survival. Defective TREM2-DAP12 functions play a central role in the pathogenesis of several diseases. The CX3CL1 (fractalkine-CX3CR1 signaling represents the most important communication channel between neurons and microglia. The expression of CX3CL1 in neurons and of its receptor CX3CR1 in microglia determines a specific interaction, playing fundamental roles in the regulation of the maturation and function of these cells. Here, we review the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes in aged microglia and the involvement of these pathways in physiological CNS aging and in age-associated neurodegenerative diseases.

  11. Neuroserpin Protects Rat Neurons and Microglia-Mediated Inflammatory Response Against Oxygen-Glucose Deprivation- and Reoxygenation Treatments in an In Vitro Study

    Directory of Open Access Journals (Sweden)

    Xuelian Yang

    2016-04-01

    Full Text Available Background/Aims: Neuroserpin (NSP is known for its neuroprotective role in cerebral ischemic animal models and patients. Our laboratory conducted a series of investigations on the neuroprotection of NSP in different cells in the brain. In the present study, we further observe the effects of NSP on neurons and microglia-mediated inflammatory response following oxygen-glucose deprivation (OGD, and explore possible mechanisms related to neuroprotection of OGD in the central nervous system (CNS. Methods: Neurons and microglia from neonatal rats were treated with OGD followed by reoxygenation (OGD/R. To confirm the effects of NSP, the neuronal survival, neuronal apoptosis, and lactate dehydrogenase (LDH release were measured in cultured neurons. Furthermore, the levels of IL-1β and nitric oxide (NO release were also detected in cultured microglia. The possible mechanisms for the neuroprotective effect of NSP were explored using Western blot analysis. Results: NSP administration can reverse abnormal variations in neurons and microglia-mediated inflammatory response induced by OGD/R processes. The neuronal survival rate, neuronal apoptosis rate, and LDH release were significantly improved by NSP administration in neurons. Simultaneously, the release of IL-1β and NO were significantly reduced by NSP in microglia. Western blot showed that the expression of ERK, P38, and JNK was upregulated in microglia by the OGD/R treatment, and these effects were significantly inhibited by NSP. Conclusion: These data verified the neuroprotective effects of NSP on neurons and microglia-mediated inflammatory response. Inhibition of the mitogen-activated protein kinase (MAPK signaling pathways might play a potential role in NSP neuroprotection on microglia-mediated inflammatory response, which needs further verification.

  12. Aldose reductase mediates retinal microglia activation

    International Nuclear Information System (INIS)

    Chang, Kun-Che; Shieh, Biehuoy; Petrash, J. Mark

    2016-01-01

    Retinal microglia (RMG) are one of the major immune cells in charge of surveillance of inflammatory responses in the eye. In the absence of an inflammatory stimulus, RMG reside predominately in the ganglion layer and inner or outer plexiform layers. However, under stress RMG become activated and migrate into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in cell culture secrete pro-inflammatory cytokines in a manner sensitive to downregulation by aldose reductase inhibitors. In this study, we utilized CX3CR1"G"F"P mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migration in vivo. When tested on an AR"W"T background, IP injection of LPS induced RMG activation and migration into the INL and ONL. However, this phenomenon was largely prevented by AR inhibitors or in AR null mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced increases in ocular levels of TNF-α and CX3CL-1 in WT mice were substantially lower in AR null mice or were reduced by AR inhibitor treatment. These studies demonstrate that AR expression in RMG may contribute to the proinflammatory phenotypes common to various eye diseases such as uveitis and diabetic retinopathy. - Highlights: • AR inhibition prevents retinal microglial activation. • Endotoxin-induced ocular cytokine production is reduced in AR null mice. • Overexpression of AR spontaneously induces retinal microglial activation.

  13. Aldose reductase mediates retinal microglia activation

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    Chang, Kun-Che; Shieh, Biehuoy; Petrash, J. Mark, E-mail: mark.petrash@ucdenver.edu

    2016-04-29

    Retinal microglia (RMG) are one of the major immune cells in charge of surveillance of inflammatory responses in the eye. In the absence of an inflammatory stimulus, RMG reside predominately in the ganglion layer and inner or outer plexiform layers. However, under stress RMG become activated and migrate into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in cell culture secrete pro-inflammatory cytokines in a manner sensitive to downregulation by aldose reductase inhibitors. In this study, we utilized CX3CR1{sup GFP} mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migration in vivo. When tested on an AR{sup WT} background, IP injection of LPS induced RMG activation and migration into the INL and ONL. However, this phenomenon was largely prevented by AR inhibitors or in AR null mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced increases in ocular levels of TNF-α and CX3CL-1 in WT mice were substantially lower in AR null mice or were reduced by AR inhibitor treatment. These studies demonstrate that AR expression in RMG may contribute to the proinflammatory phenotypes common to various eye diseases such as uveitis and diabetic retinopathy. - Highlights: • AR inhibition prevents retinal microglial activation. • Endotoxin-induced ocular cytokine production is reduced in AR null mice. • Overexpression of AR spontaneously induces retinal microglial activation.

  14. Microglia Induce Neurotoxic IL-17+ γδ T Cells Dependent on TLR2, TLR4, and TLR9 Activation.

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    Katja Derkow

    Full Text Available Interleukin-17 (IL-17 acts as a key regulator in central nervous system (CNS inflammation. γδ T cells are an important innate source of IL-17. Both IL-17+ γδ T cells and microglia, the major resident immune cells of the brain, are involved in various CNS disorders such as multiple sclerosis and stroke. Also, activation of Toll-like receptor (TLR signaling pathways contributes to CNS damage. However, the mechanisms underlying the regulation and interaction of these cellular and molecular components remain unclear.In this study, we investigated the crosstalk between γδ T cells and microglia activated by TLRs in the context of neuronal damage. To this end, co-cultures of IL-17+ γδ T cells, neurons, and microglia were analyzed by immunocytochemistry, flow cytometry, ELISA and multiplex immunoassays.We report here that IL-17+ γδ T cells but not naïve γδ T cells induce a dose- and time-dependent decrease of neuronal viability in vitro. While direct stimulation of γδ T cells with various TLR ligands did not result in up-regulation of CD69, CD25, or in IL-17 secretion, supernatants of microglia stimulated by ligands specific for TLR2, TLR4, TLR7, or TLR9 induced activation of γδ T cells through IL-1β and IL-23, as indicated by up-regulation of CD69 and CD25 and by secretion of vast amounts of IL-17. This effect was dependent on the TLR adaptor myeloid differentiation primary response gene 88 (MyD88 expressed by both γδ T cells and microglia, but did not require the expression of TLRs by γδ T cells. Similarly to cytokine-primed IL-17+ γδ T cells, IL-17+ γδ T cells induced by supernatants derived from TLR-activated microglia also caused neurotoxicity in vitro. While these neurotoxic effects required stimulation of TLR2, TLR4, or TLR9 in microglia, neuronal injury mediated by bone marrow-derived macrophages did not require TLR signaling. Neurotoxicity mediated by IL-17+ γδ T cells required a direct cell-cell contact between T

  15. The Effect of Hydroxylated Fullerene Nanoparticles on Antioxidant Defense System in Brain Ischemia Rat

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    2017-05-01

    Full Text Available Background and Objectives: According to the previous findings, brain ischemia attenuates the brain antioxidant defense system. This study aimed to investigate the effect of hydroxylated fullerene nanoparticle on antioxidant defense system in ischemic brain rat. Methods: In this Experimental study, rats were divided into three groups (n=6 in each group: sham, ischemic control, and ischemic treatment group. Brain ischemia was induced by middle cerebral artery (MCA occlusion for 90 minutes followed by a 24-hour reperfusion. Ischemic treatment animals received fullerene nanoparticles intraperitoneally at a dose of 10mg/kg immediately after the end of MCA occlusion. After 24-h reperfusion period, brain catalase and superoxide dismutase (SOD, and glutathione activities were assessed by biochemical methods. The data were analyzed using one-way ANOVA and Tukey post-hoc test. Results: The mean glutathione level and catalase and SOD activities in sham animals were 1±0.18%, 1±0.20%, and 1±0.04%, respectively. Induction of brain ischemia decreased the value of glutathione level and catalase and SOD activities in control ischemic rats and their values were obtained to be 0.55±0.09%, 0.44±0.05%, and 0.86±0.02%, respectively. Fullerene significantly increased the activities of catalase (0.93±0.29% and SOD (1.33±0.22% in ischemic treatment group compared to ischemic control rats, but did not change the glutathione level (0.52±0.25%. Conclusion: The results of this study showed that treatment with fullerene nanoparticles improves the brain antioxidant defense system, which is weakened during brain ischemia, through increasing catalase and SOD activities.

  16. Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia.

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    Beilei Lei

    Full Text Available Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO and prostaglandin E2 (PGE2, mediated by inducible NO synthase (iNOS and cyclooxygenase-2 (COX-2, respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone's effects on tumor necrosis factor alpha (TNF-α, iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB and mitogen activated protein kinase (MAPK pathways. LPS (30 ng/ml upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury.

  17. Transcriptome analysis of amoeboid and ramified microglia isolated from the corpus callosum of rat brain

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    Parakalan Rangarajan

    2012-06-01

    Full Text Available Abstract Background Microglia, the resident immune cells of the central nervous system (CNS, have two distinct phenotypes in the developing brain: amoeboid form, known to be amoeboid microglial cells (AMC and ramified form, known to be ramified microglial cells (RMC. The AMC are characterized by being proliferative, phagocytic and migratory whereas the RMC are quiescent and exhibit a slow turnover rate. The AMC transform into RMC with advancing age, and this transformation is indicative of the gradual shift in the microglial functions. Both AMC and RMC respond to CNS inflammation, and they become hypertrophic when activated by trauma, infection or neurodegenerative stimuli. The molecular mechanisms and functional significance of morphological transformation of microglia during normal development and in disease conditions is not clear. It is hypothesized that AMC and RMC are functionally regulated by a specific set of genes encoding various signaling molecules and transcription factors. Results To address this, we carried out cDNA microarray analysis using lectin-labeled AMC and RMC isolated from frozen tissue sections of the corpus callosum of 5-day and 4-week old rat brain respectively, by laser capture microdissection. The global gene expression profiles of both microglial phenotypes were compared and the differentially expressed genes in AMC and RMC were clustered based on their functional annotations. This genome wide comparative analysis identified genes that are specific to AMC and RMC. Conclusions The novel and specific molecules identified from the trancriptome explains the quiescent state functioning of microglia in its two distinct morphological states.

  18. Plasma Membrane Protein Profiling in Beta-Amyloid-Treated Microglia Cell Line.

    Science.gov (United States)

    Correani, Virginia; Di Francesco, Laura; Mignogna, Giuseppina; Fabrizi, Cinzia; Leone, Stefano; Giorgi, Alessandra; Passeri, Alessia; Casata, Roberto; Fumagalli, Lorenzo; Maras, Bruno; Schininà, M Eugenia

    2017-09-01

    In the responsiveness of microglia to toxic stimuli, plasma membrane proteins play a key role. In this study we treated with a synthetic beta amyloid peptide murine microglial cells metabolically differently labelled with stable isotope amino acids (SILAC). The plasma membrane was selectively enriched by a multi-stage aqueous two-phase partition system. We were able to identify by 1D-LC-MS/MS analyses 1577 proteins, most of them are plasma membrane proteins according to the Gene Ontology annotation. An unchanged level of amyloid receptors in this data set suggests that microglia preserve their responsiveness capability to the environment even after 24-h challenge with amyloid peptides. On the other hand, 14 proteins were observed to change their plasma membrane abundance to a statistically significant extent. Among these, we proposed as reliable biomarkers of the inflammatory microglia phenotype in AD damaged tissues MAP/microtubule affinity-regulating kinase 3 (MARK3), Interferon-induced transmembrane protein 3 (IFITM3), Annexins A5 and A7 (ANXA5, ANXA7) and Neuropilin-1 (NRP1), all proteins known to be involved in the inflammation processes and in microtubule network assembly rate. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. A Role of Fluoride on Free Radical Generation and Oxidative Stress in BV-2 Microglia Cells

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    Xi Shuhua

    2012-01-01

    Full Text Available The generation of ROS and lipid peroxidation has been considered to play an important role in the pathogenesis of chronic fluoride toxicity. In the present study, we observed that fluoride activated BV-2 microglia cell line by observing OX-42 expression in immunocytochemistry. Intracellular superoxide dismutase (SOD, glutathione (GSH, malondialdehyde (MDA, reactive oxygen species (ROS, superoxide anions (O2∙-, nitric oxide synthase (NOS, nitrotyrosine (NT and nitric oxide (NO, NOS in cell medium were determined for oxidative stress assessment. Our study found that NaF of concentration from 5 to 20 mg/L can stimuli BV-2 cells to change into activated microglia displaying upregulated OX-42 expression. SOD activities significantly decreased in fluoride-treated BV-2 cells as compared with control, and MDA concentrations and contents of ROS and O2∙- increased in NaF-treated cells. Activities of NOS in cells and medium significantly increased with fluoride concentrations in a dose-dependent manner. NT concentrations also increased significantly in 10 and 50 mg/L NaF-treated cells compared with the control cells. Our present study demonstrated that toxic effects of fluoride on the central nervous system possibly partly ascribed to activiting of microglia, which enhanced oxidative stress induced by ROS and reactive nitrogen species.

  20. Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

    Science.gov (United States)

    Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

    2017-07-01

    Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders

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    Hans O. Kalkman

    2017-12-01

    Full Text Available Atopic diseases are frequently co-morbid with autism spectrum disorders (ASD. Allergic responses are associated with an activation of mast cells, innate lymphoid cells, and Th2 cells. These cells produce type-2 cytokines (IL4 and IL13, which stimulate microglia and macrophages to adopt a phenotype referred to as ‘alternative activation’ or ‘M2A’. M2A-polarized macrophages and microglia play a physiological role in tissue repair by secreting growth factors such as brain-derived neurotrophic factor (BDNF and insulin-like growth factor-1. In ASD there is evidence for increased type-2 cytokines, microglia activation, M2A polarization, and increased levels of growth factors. In neurons, these growth factors drive a signal transduction pathway that leads to activation of the enzyme mammalian Target of Rapamycin (mTOR, and thereby to the inhibition of autophagy. Activation of mTOR is an effect that is also common to several of the genetic forms of autism. In the central nervous system, redundant synapses are removed via an autophagic process. Activation of mTOR would diminish the pruning of redundant synapses, which in the context of ASD is likely to be undesired. Based on this line of reasoning, atopic diseases like food allergy, eczema or asthma would represent risk factors for autism spectrum disorders.

  2. The established and emerging roles of astrocytes and microglia in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

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    Rowan Andrew Warren Radford

    2015-10-01

    Full Text Available Amyotrophic lateral sclerosis (ALS and Frontotemporal Dementia (FTD are two progressive, fatal neurodegenerative syndromes with considerable clinical, genetic and pathological overlap. Clinical symptoms of FTD can be seen in ALS patients and vice versa, recent genetic discoveries conclusive link the two diseases, and several common molecular players have been identified (TDP-43, FUS, C9ORF72.The definitive aetiologies of ALS and FTD are currently unknown and both disorders lack a cure. Glia, specifically astrocytes and microglia are heavily implicated in the onset and progression of neurodegeneration witnessed in ALS and FTD. In this review, we summarise the current understanding of the role of microglia and astrocytes involved in ALS and FTD, highlighting their recent implications in neuroinflammation, alterations in waste clearance involving phagocytosis and the newly described glymphatic system, and vascular abnormalities. Elucidating the precise mechanisms of how astrocytes and microglia are involved in ALS and FTD will be crucial in characterising these two disorders and may represent more effective interventions for disease progression and treatment options in the future.

  3. The established and emerging roles of astrocytes and microglia in amyotrophic lateral sclerosis and frontotemporal dementia.

    Science.gov (United States)

    Radford, Rowan A; Morsch, Marco; Rayner, Stephanie L; Cole, Nicholas J; Pountney, Dean L; Chung, Roger S

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two progressive, fatal neurodegenerative syndromes with considerable clinical, genetic and pathological overlap. Clinical symptoms of FTD can be seen in ALS patients and vice versa. Recent genetic discoveries conclusively link the two diseases, and several common molecular players have been identified (TDP-43, FUS, C9ORF72). The definitive etiologies of ALS and FTD are currently unknown and both disorders lack a cure. Glia, specifically astrocytes and microglia are heavily implicated in the onset and progression of neurodegeneration witnessed in ALS and FTD. In this review, we summarize the current understanding of the role of microglia and astrocytes involved in ALS and FTD, highlighting their recent implications in neuroinflammation, alterations in waste clearance involving phagocytosis and the newly described glymphatic system, and vascular abnormalities. Elucidating the precise mechanisms of how astrocytes and microglia are involved in ALS and FTD will be crucial in characterizing these two disorders and may represent more effective interventions for disease progression and treatment options in the future.

  4. Differential responses of the antioxidant system of ametryn and clomazone tolerant bacteria.

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    Leila Priscila Peters

    Full Text Available The herbicides ametryn and clomazone are widely used in sugarcane cultivation, and following microbial degradation are considered as soil and water contaminants. The exposure of microorganisms to pesticides can result in oxidative damage due to an increase in the production of reactive oxygen species (ROS. This study investigated the response of the antioxidant systems of two bacterial strains tolerant to the herbicides ametryn and clomazone. Bacteria were isolated from soil with a long history of ametryn and clomazone application. Comparative analyses based on 16S rRNA gene sequences revealed that strain CC07 is phylogenetically related to Pseudomonas aeruginosa and strain 4C07 to P. fulva. The two bacterial strains were grown for 14 h in the presence of separate and combined herbicides. Lipid peroxidation, reduced glutathione content (GSH and antioxidant enzymes activities were evaluated. The overall results indicated that strain 4C07 formed an efficient mechanism to maintain the cellular redox balance by producing reactive oxygen species (ROS and subsequently scavenging ROS in the presence of the herbicides. The growth of bacterium strain 4C07 was inhibited in the presence of clomazone alone, or in combination with ametryn, but increased glutathione reductase (GR and glutathione S-transferase (GST activities, and a higher GSH concentration were detected. Meanwhile, reduced superoxide dismutase (SOD, catalase (CAT and GST activities and a lower concentration of GSH were detected in the bacterium strain CC07, which was able to achieve better growth in the presence of the herbicides. The results suggest that the two bacterial strains tolerate the ametryn and clomazone herbicides with distinctly different responses of the antioxidant systems.

  5. Differential Responses of the Antioxidant System of Ametryn and Clomazone Tolerant Bacteria

    Science.gov (United States)

    Peters, Leila Priscila; Carvalho, Giselle; Martins, Paula Fabiane; Dourado, Manuella Nóbrega; Vilhena, Milca Bartz; Pileggi, Marcos; Azevedo, Ricardo Antunes

    2014-01-01

    The herbicides ametryn and clomazone are widely used in sugarcane cultivation, and following microbial degradation are considered as soil and water contaminants. The exposure of microorganisms to pesticides can result in oxidative damage due to an increase in the production of reactive oxygen species (ROS). This study investigated the response of the antioxidant systems of two bacterial strains tolerant to the herbicides ametryn and clomazone. Bacteria were isolated from soil with a long history of ametryn and clomazone application. Comparative analyses based on 16S rRNA gene sequences revealed that strain CC07 is phylogenetically related to Pseudomonas aeruginosa and strain 4C07 to P. fulva. The two bacterial strains were grown for 14 h in the presence of separate and combined herbicides. Lipid peroxidation, reduced glutathione content (GSH) and antioxidant enzymes activities were evaluated. The overall results indicated that strain 4C07 formed an efficient mechanism to maintain the cellular redox balance by producing reactive oxygen species (ROS) and subsequently scavenging ROS in the presence of the herbicides. The growth of bacterium strain 4C07 was inhibited in the presence of clomazone alone, or in combination with ametryn, but increased glutathione reductase (GR) and glutathione S-transferase (GST) activities, and a higher GSH concentration were detected. Meanwhile, reduced superoxide dismutase (SOD), catalase (CAT) and GST activities and a lower concentration of GSH were detected in the bacterium strain CC07, which was able to achieve better growth in the presence of the herbicides. The results suggest that the two bacterial strains tolerate the ametryn and clomazone herbicides with distinctly different responses of the antioxidant systems. PMID:25380132

  6. Activated Microglia Targeting Dendrimer-Minocycline Conjugate as Therapeutics for Neuroinflammation.

    Science.gov (United States)

    Sharma, Rishi; Kim, Soo-Young; Sharma, Anjali; Zhang, Zhi; Kambhampati, Siva Pramodh; Kannan, Sujatha; Kannan, Rangaramanujam M

    2017-11-15

    Brain-related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Minocycline has shown promise for the treatment of neurological diseases owing to its ability to penetrate the blood-brain barrier (BBB) and potency. Despite its potential in the clinic and in preclinical models, the high doses needed to affect a positive therapeutic response have led to side effects. Targeted delivery of minocycline to the injured site and injured cells in the brain can be highly beneficial. Systemically administered hydroxyl poly(amidoamine) (PAMAM) generation-6 (G6) dendrimers have a longer blood circulation time and have been shown to cross the impaired BBB. We have successfully prepared and characterized the in vitro efficacy and in vivo targeting ability of hydroxyl-G6 PAMAM dendrimer-9-amino-minocycline conjugate (D-mino). Minocycline is a challenging drug to carry out chemical transformations due to its inherent instability. We used a combination of a highly efficient and mild copper catalyzed azide-alkyne click reaction (CuAAC) along with microwave energy to conjugate 9-amino-minocycline (mino) to the dendrimer surface via enzyme responsive linkages. D-mino was further evaluated for anti-inflammatory and antioxidant activity in lipopolysaccharides-activated murine microglial cells. D-mino conjugates enhanced the intracellular availability of the drug due to their rapid uptake, suppressed inflammatory cytokine tumor necrosis factor α (TNF-α) production, and reduced oxidative stress by suppressing nitric oxide production, all significantly better than the free drug. Fluorescently labeled dendrimer conjugate (Cy5-D-mino) was systematically administered (intravenous, 55 mg/kg) on postnatal

  7. Antioxidant and chelating capacity of Maillard reaction products in amino acid-sugar model systems: applications for food processing.

    Science.gov (United States)

    Mondaca-Navarro, Blanca A; Ávila-Villa, Luz A; González-Córdova, Aarón F; López-Cervantes, Jaime; Sánchez-Machado, Dalia I; Campas-Baypoli, Olga N; Rodríguez-Ramírez, Roberto

    2017-08-01

    Maillard reaction products (MRP) have gained increasing interest owing to their both positive and negative effects on human health. Aqueous amino acid-sugar model systems were studied in order to evaluate the antioxidant and chelating activity of MRP under conditions similar to those of food processing. Amino acids (cysteine, glycine, isoleucine and lysine) combined with different sugars (fructose or glucose) were heated to 100 and 130 °C for 30, 60 and 90 min. Antioxidant capacity was evaluated via ABTS and DPPH free radical scavenging assays, in addition to Fe 2+ and Cu 2+ ion chelating capacity. In the ABTS assay, the cysteine-fructose model system presented the highest antioxidant activity at 7.05 µmol mL -1 (130 °C, 60 min), expressed in Trolox equivalents. In the DPPH assay, the cysteine-glucose system presented the highest antioxidant activity at 3.79 µmol mL -1 (100 °C, 90 min). The maximum rate of chelation of Fe 2+ and Cu 2+ was 96.31 and 59.44% respectively in the lysine-fructose and cysteine-glucose systems (100 °C, 30 min). The model systems presented antioxidant and chelating activity under the analyzed temperatures and heating times, which are similar to the processing conditions of some foods. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  8. Coordinated Actions of Glyoxalase and Antioxidant Defense Systems in Conferring Abiotic Stress Tolerance in Plants

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    Mirza Hasanuzzaman

    2017-01-01

    Full Text Available Being sessile organisms, plants are frequently exposed to various environmental stresses that cause several physiological disorders and even death. Oxidative stress is one of the common consequences of abiotic stress in plants, which is caused by excess generation of reactive oxygen species (ROS. Sometimes ROS production exceeds the capacity of antioxidant defense systems, which leads to oxidative stress. In line with ROS, plants also produce a high amount of methylglyoxal (MG, which is an α-oxoaldehyde compound, highly reactive, cytotoxic, and produced via different enzymatic and non-enzymatic reactions. This MG can impair cells or cell components and can even destroy DNA or cause mutation. Under stress conditions, MG concentration in plants can be increased 2- to 6-fold compared with normal conditions depending on the plant species. However, plants have a system developed to detoxify this MG consisting of two major enzymes: glyoxalase I (Gly I and glyoxalase II (Gly II, and hence known as the glyoxalase system. Recently, a novel glyoxalase enzyme, named glyoxalase III (Gly III, has been detected in plants, providing a shorter pathway for MG detoxification, which is also a signpost in the research of abiotic stress tolerance. Glutathione (GSH acts as a co-factor for this system. Therefore, this system not only detoxifies MG but also plays a role in maintaining GSH homeostasis and subsequent ROS detoxification. Upregulation of both Gly I and Gly II as well as their overexpression in plant species showed enhanced tolerance to various abiotic stresses including salinity, drought, metal toxicity, and extreme temperature. In the past few decades, a considerable amount of reports have indicated that both antioxidant defense and glyoxalase systems have strong interactions in conferring abiotic stress tolerance in plants through the detoxification of ROS and MG. In this review, we will focus on the mechanisms of these interactions and the coordinated

  9. Coordinated Actions of Glyoxalase and Antioxidant Defense Systems in Conferring Abiotic Stress Tolerance in Plants

    Science.gov (United States)

    Hasanuzzaman, Mirza; Nahar, Kamrun; Hossain, Md. Shahadat; Mahmud, Jubayer Al; Rahman, Anisur; Inafuku, Masashi; Oku, Hirosuke; Fujita, Masayuki

    2017-01-01

    Being sessile organisms, plants are frequently exposed to various environmental stresses that cause several physiological disorders and even death. Oxidative stress is one of the common consequences of abiotic stress in plants, which is caused by excess generation of reactive oxygen species (ROS). Sometimes ROS production exceeds the capacity of antioxidant defense systems, which leads to oxidative stress. In line with ROS, plants also produce a high amount of methylglyoxal (MG), which is an α-oxoaldehyde compound, highly reactive, cytotoxic, and produced via different enzymatic and non-enzymatic reactions. This MG can impair cells or cell components and can even destroy DNA or cause mutation. Under stress conditions, MG concentration in plants can be increased 2- to 6-fold compared with normal conditions depending on the plant species. However, plants have a system developed to detoxify this MG consisting of two major enzymes: glyoxalase I (Gly I) and glyoxalase II (Gly II), and hence known as the glyoxalase system. Recently, a novel glyoxalase enzyme, named glyoxalase III (Gly III), has been detected in plants, providing a shorter pathway for MG detoxification, which is also a signpost in the research of abiotic stress tolerance. Glutathione (GSH) acts as a co-factor for this system. Therefore, this system not only detoxifies MG but also plays a role in maintaining GSH homeostasis and subsequent ROS detoxification. Upregulation of both Gly I and Gly II as well as their overexpression in plant species showed enhanced tolerance to various abiotic stresses including salinity, drought, metal toxicity, and extreme temperature. In the past few decades, a considerable amount of reports have indicated that both antioxidant defense and glyoxalase systems have strong interactions in conferring abiotic stress tolerance in plants through the detoxification of ROS and MG. In this review, we will focus on the mechanisms of these interactions and the coordinated action of

  10. Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS

    DEFF Research Database (Denmark)

    Reinert, Line S; Lopušná, Katarína; Winther, Henriette

    2016-01-01

    Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced t......Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV......-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication...... is strongly increased in neurons in STING-deficient mice. Interestingly, HSV-infected microglia confer STING-dependent antiviral activities in neurons and prime type I IFN production in astrocytes through the TLR3 pathway. Thus, sensing of HSV-1 infection in the CNS by microglia through the cGAS-STING pathway...

  11. Cyclic AMP is a key regulator of M1 to M2a phenotypic conversion of microglia in the presence of Th2 cytokines.

    Science.gov (United States)

    Ghosh, Mousumi; Xu, Yong; Pearse, Damien D

    2016-01-13

    Microglia and macrophages play a central role in neuroinflammation. Pro-inflammatory cytokines trigger their conversion to a classically activated (M1) phenotype, sustaining inflammation and producing a cytotoxic environment. Conversely, anti-inflammatory cytokines polarize the cells towards an alternatively activated (M2), tissue reparative phenotype. Elucidation of the signal transduction pathways involved in M1 to M2 phenotypic conversion may provide insight into how the innate immune response can be harnessed during distinct phases of disease or injury to mediate neuroprotection and neurorepair. Microglial cells (cell line and primary) were subjected to combined cyclic adenosine monophosphate (cyclic AMP) and IL-4, or either alone, in the presence of pro-inflammatory mediators, lipopolysaccharide (LPS), or tumor necrosis factor-α (TNF-α). Their effects on the expression of characteristic markers for M1 and M2 microglia were assessed. Similarly, the M1 and M2 phenotypes of microglia and macrophages within the lesion site were then evaluated following a contusive spinal cord injury (SCI) to the thoracic (T8) spinal cord of rats and mice when the agents were administered systemically. It was demonstrated that cyclic AMP functions synergistically with IL-4 to promote M1 to M2 conversion of microglia in culture. The combination of cyclic AMP and IL-4, but neither alone, induced an Arg-1(+)/iNOS(-)cell phenotype with concomitant expression of other M2-specific markers including TG2 and RELM-α. M2-converted microglia showed ameliorated production of pro-inflammatory cytokines (TNF-α and IP-10) and reactive oxygen species, with no alteration in phagocytic properties. M2a conversion required protein kinase A (PKA), but not the exchange protein directly activated by cyclic AMP (EPAC). Systemic delivery of cyclic AMP and IL-4 after experimental SCI also promoted a significant M1 to M2a phenotypic change in microglia and macrophage population dynamics in the lesion

  12. Peculiarities of antioxidant system and iron metabolism in organism during development of tumor resistance to cisplatin.

    Science.gov (United States)

    Chekhun, V F; Lozovska, Y V; Burlaka, A P; Lukyanova, N Y; Todor, I N; Naleskina, L A

    2014-09-01

    To study in vivo the peculiarities of changes of iron metabolism and antioxidant system in dynamics of growth of Guerin carcinoma with different sensitivity to cisplatin. In order to evaluate the content of metallothionein-1 (MT-1) in tumor homogenates and blood serum of rats with cisplatin-sensitive and cisplatin-resistant Guerin carcinoma the immunoenzyme method was used. The evaluation of ceruloplasmin activity, content of "free iron" complexes, superoxide and NO-generating acti-vity of NADPH-oxidase and iNOS activity in neutrophils, blood serum and tumor homogenates was measured by EPR-spectro-scopy. Maximal accumulation of MT-1 in blood serum and tumor, more pronounced in resistant strain, at the border of latent and exponential phase of growth has been shown that is the evidence of protective role of this protein in the respect to the generation of free radical compounds. It has been determined that in animals with cisplatin-resistant strain of Guerin carcinoma, increase of "free iron" complexes is more apparent both on the level of tumor and organism on the background on increase of CP/TR ratio that is the consequence of organism antioxidant protection system disorder. Mentioned changes in metabolism of iron with its accumulation in tumor and further reprogramming of mitochondria metabolism and activity of NADPH-oxidase for non-transformed cells are favorable conditions for the formation of oxidative phenotype of tumor.

  13. Response of antioxidant system to drought stress and re-watering in Alfalfa during branching

    Science.gov (United States)

    Tina, R. R.; Shan, X. R.; Wang, Y.; Guo, S. Y.; Mao, B.; Wang, W.; Wu, H. Y.; Zhao, T. H.

    2017-11-01

    This paper aimed to reveal the response mechanism of active oxygen metabolism and antioxidant enzyme activities in Alfalfa under drought stress and re-watering, and the pot experiment was used, to explore the changes of H2O2, O2·-, electrolyte leakage conductivity and MDA, SOD, POD, CAT activity in Golden Empress (tolerant cultivar) and Sanditi (non-tolerant cultivar) under drought stress and re-watering during branching stage. Three water gradients were set up: CK (Maximum field capacity of 75%±5%), T1 (Maximum field capacity of 45%±5%), T2 (Maximum field capacity of 35%±5%) to compare, and the drought rehydration was also studied. Results: the results indicated that H2O2 content, O2·-production rate, relative conductivity and MDA content were higher than the control, and the increase extent of Golden Empress was higher than the Sanditi under drought stress and after re-watering the recovery capability of Golden Empress was also higher than the Sanditi. After 7 days of re-watering, all indexes were restored to the control level, indicating that the re-watering have compensation effect after drought. After drought stress, to weaken the damage of active oxygen Golden Empress was mainly by increasing the activity of POD and SOD, but Sanditi was mainly through the POD and CAT activity increased to effectively remove ROS. Under drought stress, active oxygen in leaves of Alfalfa increased, and thus the membrane system was damaged which lead to the increase of MDA content and relative electric conductivity. Plants play a defensive role by increasing the activity of antioxidant enzymes and scavenging reactive oxygen species. After re-watering, the stress effect was reduced, and the physiological indexes of plants were restored to the control level. In general, tolerant cultivar has stronger antioxidant properties under drought and re-watering.

  14. Multisensor system based on bisphthalocyanine nanowires for the detection of antioxidants

    International Nuclear Information System (INIS)

    Gay Martín, Mónica; Saja, José Antonio de; Muñoz, Raquel; Rodríguez-Méndez, María Luz

    2012-01-01

    Highlights: ► Sensors based on LnPc 2 nanowires can be prepared by electrodeposition (EDP). ► An electronic tongue can be constructed by combining EDP sensors with a data treatment system. ► The e-tongue is able to discriminate antioxidants of interest in the food industry. ► The fast preparation and excellent performance of these nanostructured sensors is an advantage. - Abstract: Electrophoretic deposition has been used to prepare thin films based on nanowires of three lanthanoid bisphthalocyaninates (including dysprosium, gadolinium and lutetium). Nanowires of similar structural characteristics have been obtained for the three compounds by tuning the electrophoretic conditions according to the redox properties of each phthalocyanine. The three electrodes have been used to form an array of sensors that has been employed to discriminate phenolic antioxidants of interest in the food industry including caffeic, gallic, vanillic and ferulic acids. The Principal Component Analysis (PCA) and the Partial Least Squares Discriminant Analysis (PLS-DA) of the electrochemical signals has allowed a clear discrimination of the four phenols analyzed according to the number of phenolic groups attached to the structure (monophenol, diphenol or triphenol). The PCA loading plots indicate that the three electrodes bring complementary information facilitating the discrimination of the studied solutions. In addition, good correlations between the intensity of the redox processes observed in the electrodes and the concentration of phenolic compounds have been found with detection limits in the range of 10 −5 –10 −6 mol L −1 and good reproducibility. The fast preparation of these nanowires based films and their excellent performance offer a new sensing platform for the detection of antioxidants in a fast, reliable way.

  15. Injury-stimulated Sonic hedgehog expression in microglia contributes to neuroinflammatory response in the MPTP model of Parkinson's disease

    International Nuclear Information System (INIS)

    Lee, Jeong Hwi; Chung, Young Cheul; Bok, Eugene; Lee, Hankyu; Huh, Sue Hee; Lee, Ji Eun; Jin, Byung Kwan; Ko, Hyuk Wan

    2017-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration. Here, we investigated the role of Shh in the pathologic progress of Parkinson's disease in MPTP-induced animal model system. Interestingly, we observed that Shh expression was gradually increased in MPTP affected SNpc region. Activated microglia exclusively expressed SHH in vivo and we could recapitulate Shh induction in activated cultured primary microglia cells. Using the SHH responsive Cre-loxP binary genetic reporter transgenic mouse system, we also found that most of the cell types except for oligodendrocyte in the SNpc region reacted to the SHH by MPTP injection. Taken together, activated microglia induced Shh expression and most neural cells except oligodendrocyte responded to microglia-derived SHH in MPTP-treated SN. These results suggest that SHH in activated microglia by MPTP-injection might be involved in the innate processes of recovery from neurotoxin induced injury in the PD animal model system. - Highlights: • Sonic hedgehog (Shh) was induced by MPTP neurotoxin at the Substantia Nigra (SN) in vivo. • Activated microglia are major cell type for SHH expression in vivo and in vitro. • Different types of cells in the brain, except oligodendrocyte, respond to microglia-derived SHH in SN region.

  16. Cumulative abiotic stresses and their effect on the antioxidant defense system in two species of wheat, Triticum durum Desf and Triticum aestivum L.

    OpenAIRE

    Ibrahim M.M.; Alsahli A.A.; Al-Ghamdi A.A.

    2013-01-01

    The combined effects of heat and UV-B on the antioxidant system and photosynthetic pigments were investigated in the leaves of T. durum Desf. and Triticum aestivum L. The photosynthetic pigment content, in vitro evaluation of the antioxidant system activities including DPPH radical scavenging activity, and super oxide anion radical scavenging activity were determined. In addition, the antioxidant enzyme activities, such as superoxide dismutase (SOD) and gua...

  17. Contribution of microglia-mediated neuroinflammation to retinal degenerative diseases.

    Science.gov (United States)

    Madeira, Maria H; Boia, Raquel; Santos, Paulo F; Ambrósio, António F; Santiago, Ana R

    2015-01-01

    Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy.

  18. A dual role for microglia in promoting tissue inhibitor of metalloproteinase (TIMP expression in glial cells in response to neuroinflammatory stimuli

    Directory of Open Access Journals (Sweden)

    Milner Richard

    2011-06-01

    Full Text Available Abstract Background By neutralizing the effect of the matrix metalloproteinases (MMPs, the tissue inhibitors of matrix metalloproteinases (TIMPs play a critical role in maintaining tissue proteolysis in balance. As the major reactive glial cell types in the central nervous system (CNS, microglia and astrocytes play fundamental roles in mediating tissue breakdown and repair. As such, it is important to define the TIMP expression profile in these cells, as well as the mechanisms of regulation by neuroinflammatory stimuli. Methods Primary mixed glial cultures (MGC, pure microglia, and pure astrocytes were used in this study. To study astrocytes, we employed a recently described pure astrocyte culture system, which has the major advantage of totally lacking microglia. The three different types of culture were treated with lipopolysaccharide (LPS or individual cytokines, and cell culture supernatants assayed for TIMP-1 or TIMP-2 protein expression by western blot. Results LPS induced TIMP-1 expression in MGC, but not in pure astrocyte or microglial cultures. When pure astrocytes were treated with the cytokines IL-1β, IFN-γ, TNF or TGF-β1, only IL-1β induced TIMP-1 expression. Significantly, astrocyte TIMP-1 expression was restored in LPS-treated astrocyte cultures after the addition of microglia, or conditioned medium taken from LPS-activated microglia (MG-CM. Furthermore, this effect was lost after depletion of IL-1β from MG-CM. By contrast, TIMP-2 was constitutively expressed by astrocytes, whereas microglia expressed TIMP-2 only after exposure to serum. Conclusions Taken together, these results demonstrate an important concept in glial interactions, by showing that microglia play a central role in regulating glial cell expression of TIMPs, and identify microglial IL-1β as playing a key role in mediating microglial-astrocyte communication.

  19. Effect of Juglone foliar injection on Superoxide dismutases antioxidant system in two Musa spp cultivars

    Directory of Open Access Journals (Sweden)

    Michel Leiva Mora

    2004-04-01

    Full Text Available Some diseases in higher plants cause formation of reactive oxygen species (ROS which acts like mediator on tolerance to oxidative stress. Several phytotoxins produced by plant pathogen fungus induce ROS by different mechanisms which damage plant cell tissues. This paper was focused to determine juglone impact (Psedocercospora fijiensis toxin on Superoxide dismutases antioxidant system in Fougamou (ABB and Grande naine (AAA by native Poliacrylamide gel electrophoresis (PAGE 10%. Samples of proteins were collected at 2, 4, 6, 8 and 48h after juglone injection on both Musa cultivar and 65 μl of them (120 μg of total protein were applied to gels. Gels were incubated in staining solution (25 mg.ml-1 de Nitrobluetetrazolium (NTB and 0.1 mg.ml-1 de riboflavin and were exposured to fluorescent light. In both cultivars it was observed changes in expression patterns of superoxide dismutases between injected and not injected plants. On Grande naine (AAA 4 h after injection an isoform of SOD disappeared respect to control. Nevertheless on Fougamou (ABB, 2 h after injection it was activated a new isoform which was observed until 48 h. In the present work it was observed a correspondence between protein patterns expression of SOD isoforms and tolerance to oxidative stress caused by the effect of juglone on Musa spp. Key words: antioxidant enzymes, Mycosphaerella fijiensis,oxidative stress, toxins

  20. Brassinosteroids Denigrate the Seasonal Stress through Antioxidant Defense System in Seedlings of Brassica juncea L.

    Directory of Open Access Journals (Sweden)

    Sandeep Kumar

    2014-05-01

    Full Text Available The present work has been undertaken to study the effect of exogenously application of 24-epiBL and 28-homoBL on soluble protein, proline contents and antioxidant defense system of Brassica juncea L. RLM 619 under the influence of seasonal stress. It was observed that 24-epiBL and 28-homoBL treatment enhance the soluble protein, dry weight and shoot length of B. juncea seedlings under seasonal stress. If seeds treated with the different concentrations (10-6, 10-8 and 10-10 M of 24-epiBL and 28-homoBL revealed batter growth, protein and proline contents as compare to untreated seedlings. Similarly the activities of antioxidant enzymes SOD, CAT, APOX, DHAR, PPO and Auxinases were enhanced by the application of different concentration of both brassinosteroids, whereas MDA content was decrease with both brassinosteroids treatments. Then we have concluded that both brassinolides have the seasonal stress ameliorative properties in B. juncea seedlings grown under the influence of seasonal stress. This study culminates to the role of brassinolides as an anti-stress property for protection of plant from various types of stresses.

  1. Antioxidant and Ex Vivo Immune System Regulatory Properties of Boswellia serrata Extracts

    Directory of Open Access Journals (Sweden)

    Daniela Beghelli

    2017-01-01

    Full Text Available Boswellia serrata (BS is an important traditional medicinal plant that currently represents an interesting topic for pharmaceutical research since it possesses several pharmacological properties (e.g., anti-inflammatory, antimicrobial, and antitumour. The safety and versatility of this dietary supplement should allow for its use in numerous pathological conditions; however the quality of the extracts needs to be standardized to increase the clinical success rate resulting from its use. In the present study, different commercially available B. serrata extracts were employed to compare their AKBA content and in vitro antioxidant power. Furthermore, their ability to modulate the immune system regulatory properties was investigated. Our results showed that the AKBA content varied from 3.83±0.10 to 0.03±0.004%, with one sample in which it was not detectable. The highest antioxidant power and phenolic content were shown by the same extract, which also exhibited the highest AKBA concentration. Finally, the BS extracts showed the ability to influence the regulatory and effector T-cell compartments. Our results suggest that frankincense should be further investigated for its promising potentiality to modulate not only inflammation/oxidative stress but also immune dysregulation, but attention should be paid to the composition of the commercial extracts.

  2. Responses of Phospholipase D and Antioxidant System to Mechanical Wounding in Postharvest Banana Fruits

    Directory of Open Access Journals (Sweden)

    Li Li

    2017-01-01

    Full Text Available Banana fruits are susceptible to mechanical damage. The present study was to investigate the responses of phospholipase D (PLD and antioxidant system to mechanical wounding in postharvest banana fruits. During 16 d storage at 25°C and 90% relative humidity, PLD activity in wounded fruits was significantly higher than that in control (without artificial wounding fruits. The higher value of PLD mRNA was found in wounded fruits than in control. PLD mRNA expression reached the highest peak on day 4 in both groups, but it was 2.67 times in wounded fruits compared to control at that time, indicating that PLD gene expression was activated in response to wounding stress. In response to wounding stress, the higher lipoxygenase (LOX activity was observed and malondialdehyde (MDA production was accelerated. The activities of antioxidant enzymes such as superoxide dismutase (SOD, catalase (CAT, peroxidase (POD, and ascorbate peroxidase (APX in wounded fruits were significantly higher than those in control. The concentrations of reactive oxygen species (ROS such as superoxide anion (O2•- and hydrogen peroxide (H2O2 in fruits increased under mechanical wounding. The above results provided a basis for further investigating the mechanism of postharvest banana fruits adapting to environmental stress.

  3. Comparison of an antioxidant system in tolerant and susceptible wheat seedlings in response to salt stress

    Energy Technology Data Exchange (ETDEWEB)

    Feki, K.; Tounsi, S.; Brini, F.

    2017-07-01

    It has been demonstrated previously that the physiological and molecular analysis of seedlings of the tolerant (Om Rabia3) and susceptible (Mahmoudi) Tunisian wheat genotypes were different at short and long-term response to salinity. In this study, we examined the antioxidant defence system in seedlings of these two cultivars at short-term response to different NaCl concentrations. The findings showed that high salinity tolerance of cv. Om Rabia3, as manifested by lower decrease in its dry biomass, was associated with lower malondialdehyde and hydrogen peroxide contents, lower accumulation of the superoxide (O2⎯) in the roots and the shoots, and also lower decrease in ascorbate content than those in cv. Mahmoudi. Moreover, the expression of some genes coding for antioxidant enzymes such as the catalase, the superoxide dismutase and the peroxidase were enhanced by NaCl stress especially in the salt-tolerant cultivar. In parallel, their activities were increased in response to the same condition of stress and especially in the cv. Om Rabia3. Taken together, these data suggested that the capacity to limit oxidative damage is important for NaCl tolerance of durum wheat.

  4. Thyroid Hormones and Antioxidant Systems: Focus on Oxidative Stress in Cardiovascular and Pulmonary Diseases

    Directory of Open Access Journals (Sweden)

    Antonio Mancini

    2013-12-01

    Full Text Available In previous works we demonstrated an inverse correlation between plasma Coenzyme Q10 (CoQ10 and thyroid hormones; in fact, CoQ10 levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ10 is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. A Low-T3 syndrome is a condition observed in several chronic diseases: it is considered an adaptation mechanism, where there is a reduction in pro-hormone T4 conversion. Low T3-Syndrome is not usually considered to be corrected with replacement therapy. We review the role of thyroid hormones in regulation of antioxidant systems, also presenting data on total antioxidant capacity and Coenzyme Q10. Published studies suggest that oxidative stress could be involved in the clinical course of different heart diseases; our data could support the rationale of replacement therapy in low-T3 conditions.

  5. Modulation of Fibrosis in Systemic Sclerosis by Nitric Oxide and Antioxidants

    Directory of Open Access Journals (Sweden)

    Audrey Dooley

    2012-01-01

    Full Text Available Systemic sclerosis (scleroderma: SSc is a multisystem, connective tissue disease of unknown aetiology characterized by vascular dysfunction, autoimmunity, and enhanced fibroblast activity resulting in fibrosis of the skin, heart, and lungs, and ultimately internal organ failure, and death. One of the most important and early modulators of disease activity is thought to be oxidative stress. Evidence suggests that the free radical nitric oxide (NO, a key mediator of oxidative stress, can profoundly influence the early microvasculopathy, and possibly the ensuing fibrogenic response. Animal models and human studies have also identified dietary antioxidants, such as epigallocatechin-3-gallate (EGCG, to function as a protective system against oxidative stress and fibrosis. Hence, targeting EGCG may prove a possible candidate for therapeutic treatment aimed at reducing both oxidant stress and the fibrotic effects associated with SSc.

  6. Diabetic nephropathy and antioxidants.

    Science.gov (United States)

    Tavafi, Majid

    2013-01-01

    Oxidative stress has crucial role in pathogenesis of diabetic nephropathy (DN). Despite satisfactory results from antioxidant therapy in rodent, antioxidant therapy showed conflicting results in combat with DN in diabetic patients. Directory of Open Access Journals (DOAJ), Google Scholar,Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Treatment of DN in human are insufficient with rennin angiotensin system (RAS) blockers, so additional agent ought to combine with this management. Meanwhile based on DN pathogenesis and evidences in experimental and human researches, the antioxidants are the best candidate. New multi-property antioxidants may be improved human DN that show high power antioxidant capacity, long half-life time, high permeability to mitochondrion, improve body antioxidants enzymes activity and anti-inflammatory effects. Based on this review and our studies on diabetic rats, rosmarinic acid a multi-property antioxidant may be useful in DN patients, but of course, needs to be proven in clinical trials studies.

  7. Fate of the synergistic antioxidant system ascorbic acid, lecithin, and tocopherol in mayonnaise : Partition of ascorbic acid

    DEFF Research Database (Denmark)

    Meyer, A.S.; Jacobsen, Charlotte Munch

    1996-01-01

    The distribution of ascorbic acid between the lipid and aqueous phase was investigated in mayonnaises enriched with fish oil containing a synergistic antioxidant mixture of ascorbic acid, lecithin and gamma-tocopherol, i.e., the A/L/T system (Loliger and Saucy 1989). The ascorbic acid was found...... to be located in the aqueous phase indicating that the A/L/T system broke down in mayonnaises. Based on the hypothesis that synergistic antioxidant action between ascorbic acid, lecithin and tocopherol requires that the three components are in close assembly, the results offer an explanation as to why the A...

  8. Effects of Food Based Yeast on Oxidant-Antioxidant Systems in Rats fed by High Cholesterol Diet

    OpenAIRE

    Savaş, Hasan Basri; Yüksel, Özlem; Şanlıdere Aloğlu, Hatice; Öner, Zübeyde; Demir Özer, Ezgi; Gültekin, Fatih

    2013-01-01

    In living organisms, oxidant and antioxidant systems are in a balance. In the present study, our aim was to study the effects of Cryptococcus humicola, which is a food based yeast whose cholesterol lowering activity is under investigation, on oxidant and antioxidant systems.31 adult male, Wistar albino rats weighing 200-250 gr were included in the study. Rats were divided into four groups based on their diets. Group 1(Control Group) was fed a normal diet, Group 2 was fed a high cholesterol di...

  9. Antioxidant activity and sensory analysis of murtilla (Ugni molinae Turcz.) fruit extracts in an oil model system

    International Nuclear Information System (INIS)

    Augusto-Obara, T.R.; Pirce, F.; Scheuermann, E.; Spoto, M.H.F.; Vieira, T.M.F.S.

    2017-01-01

    An oil model system was used to analyze the antioxidant activity of Chilean fruit extracts and to determine their odor sensory effect. Hydroalcoholic extracts from wild and 14-4 genotype murtilla (Ugni molinae Turcz.) fruit were assessed by the Response Surface Methodology. The optimal conditions for producing high total phenolic-content extracts were 49.5% (v/v) ethanol at 30 ºC, which yielded 18.39 and 26.14 mg GAE·g−1 dry matter, respectively. The optimized extracts were added to a lipid model system and evaluated via the Schaal Oven Test. After 96 hours, 150 and 200 mg·kg−1 oil of the wild and 14-4 genotype extracts, respectively, showed an antioxidant capacity similar to TBHQ (200 mg·kg−1 oil) in terms of peroxide values and odor. Thus, murtilla fruit extracts are a natural source of antioxidants for protecting lipidic foods, such as soybean oil. [es

  10. Neuron-microglia interactions in mental health disorders: 'For better, and for worse'

    Directory of Open Access Journals (Sweden)

    Eric S Wohleb

    2016-11-01

    Full Text Available Persistent cognitive and behavioral symptoms that characterize many mental health disorders arise from impaired neuroplasticity in several key corticolimbic brain regions. Recent evidence suggest that reciprocal neuron-microglia interactions shape neuroplasticity during physiological conditions, implicating microglia in the neurobiology of mental health disorders. Neuron-microglia interactions are modulated by several molecular and cellular pathways and dysregulation of these pathways often have neurobiological consequences, including aberrant neuronal responses and microglia activation. The interactions between neurons and microglia have implications for mental health disorders as rodent stress models cause concomitant neuronal dystrophy and alterations in microglia morphology and function. In this context, functional changes in microglia may be indicative of an immune state termed parainflammation in which tissue-resident macrophages (i.e., microglia respond to malfunctioning cells by initiating modest inflammation in an attempt to restore homeostasis. Thus, aberrant neuronal activity and release of damage-associated signals during repeated stress exposure may contribute to functional changes in microglia and resultant parainflammation. Furthermore, accumulating evidence shows that uncoupling neuron-microglia interactions may contribute to altered neuroplasticity and associated anxiety- or depressive-like behaviors. Additional work shows that microglia have varied phenotypes in specific brain regions, which may underlie divergent neuroplasticity observed in corticolimbic structures following stress exposure. These findings indicate that neuron-microglia interactions are critical mediators of the interface between adaptive, homeostatic neuronal function and the neurobiology of mental health disorders.

  11. Proliferating resident microglia express the stem cell antigen CD34 in response to acute neural injury

    DEFF Research Database (Denmark)

    Ladeby, Rune; Wirenfeldt, Martin; Dalmau, Ishar

    2005-01-01

    -activated microglia in the facial motor nucleus following peripheral axotomy. The results suggest lesion-reactive microglia to consist of functionally distinct subpopulations of cells; a major population of activated resident CD34(+)Mac-1(+) microglia with a high capacity for self-renewal, and a subpopulation of CD34...

  12. Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD.

    Directory of Open Access Journals (Sweden)

    Wenxin Ma

    2009-11-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD.In this study, we examined the effects of retinal microglia on RPE cells using 1 an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2 an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1 changes in RPE structure and distribution, 2 increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3 increased extent of in vivo choroidal neovascularization in the subretinal space.These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.

  13. Identification of Glial Activation Markers by Comparison of Transcriptome Changes between Astrocytes and Microglia following Innate Immune Stimulation.

    Science.gov (United States)

    Madeddu, Silvia; Woods, Tyson A; Mukherjee, Piyali; Sturdevant, Dan; Butchi, Niranjan B; Peterson, Karin E

    2015-01-01

    The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS). Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis. Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction. Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not. Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS. In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection. Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.

  14. Identification of Glial Activation Markers by Comparison of Transcriptome Changes between Astrocytes and Microglia following Innate Immune Stimulation.

    Directory of Open Access Journals (Sweden)

    Silvia Madeddu

    Full Text Available The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS. Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis. Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction. Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not. Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS. In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection. Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.

  15. Effects of geographical origin, variety and farming system on the chemical markers and in vitro antioxidant capacity of Brazilian purple grape juices

    NARCIS (Netherlands)

    Margraf, Tiago; Santos, Érica Neulyana Taborda; Andrade, de Eriel Forville; Ruth, van Saskia M.; Granato, Daniel

    2016-01-01

    The effects of farming system, geographical origin, and grape variety on the in vitro antioxidant capacity, some physicochemical properties and chemical composition were investigated. Major and minor phenolic compounds, reducing and antioxidant assays using chemical and biological systems were

  16. Edaravone Attenuates the Proinflammatory Response in Amyloid-β-Treated Microglia by Inhibiting NLRP3 Inflammasome-Mediated IL-1β Secretion

    Directory of Open Access Journals (Sweden)

    Hong-Mei Wang

    2017-10-01

    Full Text Available Background/Aims: Microglial activation is an important pathological feature in the brains of patients with Alzheimer’s disease (AD, and amyloid-β (Aβ peptides play a crucial role in microglial activation. In addition, edaravone (EDA was recently shown to suppress oxidative stress and proinflammatory cytokine production in APPswePS1dE9 (APP/PS1 mice. However, the mechanism by which EDA inhibits the Aβ-induced proinflammatory response in microglia is poorly understood. Methods: The mitochondrial membrane potential (∆ψm was evaluated using JC-1 staining. Intracellular reactive oxygen species (ROS and mitochondrial ROS levels were detected using CM-H2DCFDA and MitoSOXTM Red, respectively. The levels of CD11b, NLRP3, pro-caspase-1 and manganese superoxide dismutase (SOD-2 were observed by western blotting, and the levels of interleukin-1beta (IL-1β in culture supernatants were quantified using an ELISA kit. Results: Aβ induced microglia activation and mitochondrial dysfunction. In addition, mitochondrial dysfunction was associated with ROS accumulation and activation of the NLRP3 inflammasome. Importantly, Aβ induced activation of the NLRP3 inflammasome, leading to caspase-1 activation and IL-1β release in microglia. Moreover, EDA obviously attenuated the depolarization of ∆ψm, reduced mitochondria-derived ROS production and increased SOD-2 activity, resulting in the suppression of NLRP3 inflammasome-mediated IL-1β secretion in Aβ-treated microglia. Conclusion: EDA is a mitochondria-targeted antioxidant and exhibits anti-inflammatory effects on Aβ-treated microglia.

  17. An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

    Science.gov (United States)

    Bath, Sundeep

    2015-01-01

    Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment. PMID:26180596

  18. Involvement of Heme Oxygenase-1 Induction in the Cytoprotective and Immunomodulatory Activities of Viola patrinii in Murine Hippocampal and Microglia Cells

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    Bin Li

    2012-01-01

    Full Text Available A number of diseases that lead to injury of the central nervous system are caused by oxidative stress and inflammation in the brain. In this study, NNMBS275, consisting of the ethanol extract of Viola patrinii, showed potent antioxidative and anti-inflammatory activity in murine hippocampal HT22 cells and BV2 microglia. NNMBS275 increased cellular resistance to oxidative injury caused by glutamate-induced neurotoxicity and reactive oxygen species generation in HT22 cells. In addition, the anti-inflammatory effects of NNMBS275 were demonstrated by the suppression of proinflammatory mediators, including proinflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2 and cytokines (tumor necrosis factor-α and interleukin-1β. Furthermore, we found that the neuroprotective and anti-inflammatory effects of NNMBS275 were linked to the upregulation of nuclear transcription factor-E2-related factor 2-dependent expression of heme oxygenase-1 in HT22 and BV2 cells. These results suggest that NNMBS275 possesses therapeutic potential against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.

  19. Application of Ultrasound in a Closed System: Optimum Condition for Antioxidants Extraction of Blackberry (Rubus fructicosus) Residues.

    Science.gov (United States)

    Zafra-Rojas, Quinatzin Y; Cruz-Cansino, Nelly S; Quintero-Lira, Aurora; Gómez-Aldapa, Carlos A; Alanís-García, Ernesto; Cervantes-Elizarrarás, Alicia; Güemes-Vera, Norma; Ramírez-Moreno, Esther

    2016-07-21

    Blackberry processing generates up to 20% of residues composed mainly of peel, seeds and pulp that are abundant in flavonoids. The objective of this study was to optimize the ultrasound conditions, in a closed system, for antioxidants extraction, using the response surface methodology. Blackberry (Rubus fructicosus) residues were analyzed for total phenolics, total anthocyanins, and antioxidant activity by ABTS and DPPH. The selected independent variables were ultrasound amplitude (X₁: 80%-90%) and extraction time (X₂: 10-15 min), and results were compared with conventional extraction methods. The optimal conditions for antioxidants extraction were 91% amplitude for 15 min. The results for total phenolic content and anthocyanins and antioxidant activity by ABTS and DPPH were of 1201.23 mg gallic acid equivalent (GAE)/100 g dry weight basis (dw); 379.12 mg/100 g·dw; 6318.98 µmol Trolox equivalent (TE)/100 g·dw and 9617.22 µmol TE/100 g·dw, respectively. Compared to solvent extraction methods (water and ethanol), ultrasound achieved higher extraction of all compounds except for anthocyanins. The results obtained demonstrated that ultrasound is an alternative to improve extraction yield of antioxidants from fruit residues such as blackberry.

  20. The Indispensable Roles of Microglia and Astrocytes during Brain Development

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    Reemst, K.; Noctor, S.C.; Lucassen, P.J.; Hol, E.M.

    2016-01-01

    Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same

  1. Directed Differentiation of Human Pluripotent Stem Cells to Microglia

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    Panagiotis Douvaras

    2017-06-01

    Full Text Available Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs. Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers. Analyses of gene expression and cytokine release showed close similarities between iPSC-derived (iPSC-MG and human primary microglia as well as clear distinctions from macrophages. iPSC-MG were able to phagocytose and responded to ADP by producing intracellular Ca2+ transients, whereas macrophages lacked such response. The differentiation protocol was highly reproducible across several pluripotent stem cell lines.

  2. Love and death: microglia, NLRP3 and the Alzheimer's brain.

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    Goldmann, Tobias; Tay, Tuan Leng; Prinz, Marco

    2013-05-01

    Microglia were previously attributed to be vital brain guardians for neuronal survival and synaptic pruning during development as well as for the brain's fight against environmental pathogens. A new report in Nature by the Heneka, Latz and Golenbock groups, however, sheds new light on these distinct myeloid cells by revealing their deadly nature for mature neurons during neurodegeneration.

  3. Activated microglia in the spinal cord underlies diabetic neuropathic pain.

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    Wang, Dongmei; Couture, Réjean; Hong, Yanguo

    2014-04-05

    Diabetes mellitus is an increasingly common chronic medical condition. Approximately 30% of diabetic patients develop neuropathic pain, manifested as spontaneous pain, hyperalgesia and allodynia. Hyperglycemia induces metabolic changes in peripheral tissues and enhances oxidative stress in nerve fibers. The damages and subsequent reactive inflammation affect structural properties of Schwann cells and axons leading to the release of neuropoietic mediators, such as pro-inflammatory cytokines and pro-nociceptive mediators. Therefore, diabetic neuropathic pain (DNP) shares some histological features and underlying mechanisms with traumatic neuropathy. DNP displays, however, other distinct features; for instance, sensory input to the spinal cord decreases rather than increasing in diabetic patients. Consequently, development of central sensitization in DNP involves mechanisms that are distinct from traumatic neuropathic pain. In DNP, the contribution of spinal cord microglia activation to central sensitization and pain processes is emerging as a new concept. Besides inflammation in the periphery, hyperglycemia and the resulting production of reactive oxygen species affect the local microenvironment in the spinal cord. All these alterations could trigger resting and sessile microglia to the activated phenotype. In turn, microglia synthesize and release pro-inflammatory cytokines and neuroactive molecules capable of inducing hyperactivity of spinal nociceptive neurons. Hence, it is imperative to elucidate glial mechanisms underlying DNP for the development of effective therapeutic agents. The present review highlights the recent developments regarding the contribution of spinal microglia as compelling target for the treatment of DNP. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. The indispensable roles of microglia and astrocytes during brain development

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    Reemst, Kitty; Noctor, Stephen C.; Lucassen, Paul J.; Hol, Elly M.

    2016-01-01

    Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same

  5. Histone deacetylase inhibitors suppress immune activation in primary mouse microglia

    NARCIS (Netherlands)

    Kannan, Vishnu; Brouwer, Nieske; Hanisch, Uwe-Karsten; Regen, Tommy; Eggen, Bart J. L.; Boddeke, Hendrikus W. G. M.

    Neuroinflammation is required for tissue clearance and repair after infections or insults. To prevent excessive damage, it is crucial to limit the extent of neuroinflammation and thereby the activation of its principal effector cell, microglia. The two main major innate immune cell types in the CNS

  6. Comparison of influence of carmustine and new proline analog of nitrosourea on antioxidant system in breast carcinoma cells (MCF-7).

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    Stankiewicz-Kranc, Anna; Miltyk, Wojciech; Skrzydlewska, Elzbieta

    2010-01-01

    The high toxicity and low selectivity of carmustine restrict its application in anticancer therapy. Therefore, proline analogs of nitrosourea have been synthesized to obtain compounds whose action on neoplastic cells is characterized by higher selectivity. The present studies have aimed at examining the influence of carmustine and a new proline analog of nitrosourea on the redox system of fibroblasts and breast cancer cells (MCF-7). Carmustine and the proline analog of nitrosourea caused an increase in hydrogen peroxide concentration both in fibroblasts and MCF-7 cells. Moreover, administration of carmustine and the new analog of nitrosourea caused a decrease in the activity of antioxidant enzymes. Observed changes in the antioxidant system correlated with an increase in concentration of dityrosine, as well as a decrease in tryptophan concentration. Changes in the antioxidant system were also accompanied by intensification of the lipid peroxidation process. In conclusion, carmustine and proline analog of nitrosourea produce similar changes in the antioxidant system in normal and cancer cells and are responsible for oxidative stress.

  7. Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection

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    Sauder Christian

    2008-11-01

    Full Text Available Abstract Neonatal Borna disease virus (BDV infection of the rat brain is associated with microglial activation and damage to certain neuronal populations. Since persistent BDV infection of neurons is nonlytic in vitro, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brains remain unclear. Our previous studies have shown that activation of microglia by BDV in culture requires the presence of astrocytes as neither the virus nor BDV-infected neurons alone activate microglia. Here, we evaluated the mechanisms whereby astrocytes can contribute to activation of microglia in neuron-glia-microglia mixed cultures. We found that persistent infection of neuronal cells leads to activation of uninfected astrocytes as measured by elevated expression of RANTES. Activation of astrocytes then produces activation of microglia as evidenced by increased formation of round-shaped, MHCI-, MHCII- and IL-6-positive microglia cells. Our analysis of possible molecular mechanisms of activation of astrocytes and/or microglia in culture indicates that the mediators of activation may be soluble heat-resistant, low molecular weight factors. The findings indicate that astrocytes may mediate activation of microglia by BDV-infected neurons. The data are consistent with the hypothesis that microglia activation in the absence of neuronal damage may represent initial steps in the gradual neurodegeneration observed in brains of neonatally BDV-infected rats.

  8. Microglia from neurogenic and non-neurogenic regions display differential proliferative potential and neuroblast support

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    Gregory Paul Marshall

    2014-07-01

    Full Text Available Microglia isolated from the neurogenic subependymal zone (SEZ and hippocampus (HC are capable of massive in vitro population expansion that is not possible with microglia isolated from non-neurogenic regions. We asked if this regional heterogeneity in microglial proliferative capacity is cell intrinsic, or is conferred by interaction with respective neurogenic or non-neurogenic niches. By combining SEZ and cerebral cortex (CTX primary tissue dissociates to generate heterospatial cultures, we find that exposure to the SEZ environment does not enhance CTX microglia expansion; however, the CTX environment exerts a suppressive effect on SEZ microglia expansion. Furthermore, addition of purified donor SEZ microglia to either CTX- or SEZ-derived cultures suppresses the expansion of host microglia, while the addition of donor CTX microglia enhances the over-all microglia yield. These data suggest that SEZ and CTX microglia possess intrinsic, spatially restricted characteristics that are independent of their in vitro environment, and that they represent unique and functionally distinct populations. Finally, we determined that the repeated supplementation of neurogenic SEZ cultures with expanded SEZ microglia allows for sustained levels of inducible neurogenesis, provided that the ratio of microglia to total cells remains within a fairly narrow range.

  9. Stereoselective phytotoxicity of HCH mediated by photosynthetic and antioxidant defense systems in Arabidopsis thaliana.

    Science.gov (United States)

    Zhang, Qiong; Zhou, Cong; Zhang, Quan; Qian, Haifeng; Liu, Weiping; Zhao, Meirong

    2013-01-01

    Hexachlorocyclohexane (HCH) has been used for plant protection and sanitation world-widely, and its isomers have been detected in water, soil, and air as well as in vegetation. As a sink for lipophilic pollutants, vegetation is very important for the degradation and fate of organic contamination; however, little was known about their phytotoxicity and mechanisms of toxic effect. In this study, the stereoselective phototoxicity of four isomers (α, β, γ, and δ) of HCHs mediated by independent as well as interconnecting systems of photosynthesis and enzymatic antioxidant defense system in Arabidopsis thaliana were assessed. Our results revealed that all the HCHs not only stimulated the activities of catalase (CAT) and peroxidase (POD), but also inhibited the activity of superoxide dismutase (SOD). In photosynthesis system, the photosynthetic efficiency of PSI and PSII were all down regulated. Meanwhile, results from both systems showed that δ-HCH was the most toxic one, while α-HCH the least in Arabidopsis thaliana. For the first time, stereoselective effects of different isomers of HCH in plant were demonstrated. And the results suggest that it requires further research to fully elucidate the environmental toxicity and their mechanisms.

  10. Stereoselective phytotoxicity of HCH mediated by photosynthetic and antioxidant defense systems in Arabidopsis thaliana.

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    Qiong Zhang

    Full Text Available BACKGROUND: Hexachlorocyclohexane (HCH has been used for plant protection and sanitation world-widely, and its isomers have been detected in water, soil, and air as well as in vegetation. As a sink for lipophilic pollutants, vegetation is very important for the degradation and fate of organic contamination; however, little was known about their phytotoxicity and mechanisms of toxic effect. In this study, the stereoselective phototoxicity of four isomers (α, β, γ, and δ of HCHs mediated by independent as well as interconnecting systems of photosynthesis and enzymatic antioxidant defense system in Arabidopsis thaliana were assessed. PRINCIPAL FINDINGS: Our results revealed that all the HCHs not only stimulated the activities of catalase (CAT and peroxidase (POD, but also inhibited the activity of superoxide dismutase (SOD. In photosynthesis system, the photosynthetic efficiency of PSI and PSII were all down regulated. Meanwhile, results from both systems showed that δ-HCH was the most toxic one, while α-HCH the least in Arabidopsis thaliana. CONCLUSIONS: For the first time, stereoselective effects of different isomers of HCH in plant were demonstrated. And the results suggest that it requires further research to fully elucidate the environmental toxicity and their mechanisms.

  11. Microglia Dictate the Impact of Saturated Fat Consumption on Hypothalamic Inflammation and Neuronal Function

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    Martin Valdearcos

    2014-12-01

    Full Text Available Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH. Here, we show that microglia mediate this process and its functional impact. Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs, only the microglia undergo inflammatory activation, along with a buildup of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high.

  12. Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function

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    Kathryn M. Lenz

    2018-04-01

    Full Text Available Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer’s disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

  13. Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function.

    Science.gov (United States)

    Lenz, Kathryn M; Nelson, Lars H

    2018-01-01

    Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

  14. Bioinspired near-infrared-excited sensing platform for in vitro antioxidant capacity assay based on upconversion nanoparticles and a dopamine-melanin hybrid system.

    Science.gov (United States)

    Wang, Dong; Chen, Chuan; Ke, Xuebin; Kang, Ning; Shen, Yuqing; Liu, Yongliang; Zhou, Xi; Wang, Hongjun; Chen, Changqing; Ren, Lei

    2015-02-11

    A novel core-shell structure based on upconversion fluorescent nanoparticles (UCNPs) and dopamine-melanin has been developed for evaluation of the antioxidant capacity of biological fluids. In this approach, dopamine-melanin nanoshells facilely formed on the surface of UCNPs act as ultraefficient quenchers for upconversion fluorescence, contributing to a photoinduced electron-transfer mechanism. This spontaneous oxidative polymerization of the dopamine-induced quenching effect could be effectively prevented by the presence of various antioxidants (typically biothiols, ascorbic acid (Vitamin C), and Trolox). The chemical response of the UCNPs@dopamine-melanin hybrid system exhibited great selectivity and sensitivity toward antioxidants relative to other compounds at 100-fold higher concentration. A satisfactory correlation was established between the ratio of the "anti-quenching" fluorescence intensity and the concentration of antioxidants. Besides the response of the upconversion fluorescence signal, a specific evaluation process for antioxidants could be visualized by the color change from colorless to dark gray accompanied by the spontaneous oxidation of dopamine. The near-infrared (NIR)-excited UCNP-based antioxidant capacity assay platform was further used to evaluate the antioxidant capacity of cell extracts and human plasma, and satisfactory sensitivity, repeatability, and recovery rate were obtained. This approach features easy preparation, fluorescence/visual dual mode detection, high specificity to antioxidants, and enhanced sensitivity with NIR excitation, showing great potential for screening and quantitative evaluation of antioxidants in biological systems.

  15. Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative

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    Victoria Navarro

    2018-05-01

    Full Text Available Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity play a central role. In other degenerative processes, such as Alzheimer’s disease (AD, the role of microglia is far to be elucidated. In this “mini-review” article, we briefly highlight our recent data comparing the microglial response between amyloidogenic transgenic models, such as APP/PS1 and AD patients. Since the AD pathology could display regional heterogeneity, we focus our work at the hippocampal formation. In APP based models a prominent microglial response is triggered around amyloid-beta (Aβ plaques. These strongly activated microglial cells could drive the AD pathology and, in consequence, could be implicated in the neurodegenerative process observed in models. On the contrary, the microglial response in human samples is, at least, partial or attenuated. This patent difference could simply reflect the lower and probably slower Aβ production observed in human hippocampal samples, in comparison with models, or could reflect the consequence of a chronic long-standing microglial activation. Beside this differential response, we also observed microglial degeneration in Braak V–VI individuals that, indeed, could compromise their normal role of surveying the brain environment and respond to the damage. This microglial degeneration, particularly relevant at the dentate gyrus, might be mediated by the accumulation of toxic soluble phospho-tau species. The consequences of this probably deficient immunological protection, observed in AD patients, are unknown.

  16. Effects of Dietary Lycopene Supplementation on Plasma Lipid Profile, Lipid Peroxidation and Antioxidant Defense System in Feedlot Bamei Lamb

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    Hongqin Jiang

    2015-07-01

    Full Text Available Lycopene, a red non-provitamin A carotenoid, mainly presenting in tomato and tomato byproducts, has the highest antioxidant activity among carotenoids because of its high number of conjugated double bonds. The objective of this study was to investigate the effect of lycopene supplementation in the diet on plasma lipid profile, lipid peroxidation and antioxidant defense system in feedlot lamb. Twenty-eight Bamei male lambs (90 days old were divided into four groups and fed a basal diet (LP0, 40:60 roughage: concentrate or the basal diet supplemented with 50, 100, and 200 mg/kg lycopene. After 120 days of feeding, all lambs were slaughtered and sampled. Dietary lycopene supplementation significantly reduced the levels of plasma total cholesterol (p0.05. The levels of TG (p<0.001 and LDL-C (p<0.001 were decreased with the feeding time extension, and both showed a linear trend (p<0.01. Malondialdehyde level in plasma and liver decreased linearly with the increase of lycopene inclusion levels (p<0.01. Dietary lycopene intake linearly increased the plasma antioxidant vitamin E level (p<0.001, total antioxidant capacity (T-AOC, p<0.05, and activities of catalase (CAT, p<0.01, glutathione peroxidase (GSH-Px, p<0.05 and superoxide dismutase (SOD, p<0.05. The plasma T-AOC and activities of GSH-Px and SOD decreased with the extension of the feeding time. In liver, dietary lycopene inclusion showed similar antioxidant effects with respect to activities of CAT (p<0.05, linearly and SOD (p<0.001, linearly. Therefore, it was concluded that lycopene supplementation improved the antioxidant status of the lamb and optimized the plasma lipid profile, the dosage of 200 mg lycopene/kg feed might be desirable for growing lambs to prevent environment stress and maintain normal physiological metabolism.

  17. Cultivated Sea Lettuce is a Multiorgan Protector from Oxidative and Inflammatory Stress by Enhancing the Endogenous Antioxidant Defense System

    Science.gov (United States)

    Ratnayake, Ranjala; Liu, Yanxia; Paul, Valerie J.; Luesch, Hendrik

    2013-01-01

    The health-promoting effects of seaweeds have been linked to antioxidant activity that may counteract cancer-causing oxidative stress-induced damage and inflammation. While antioxidant activity is commonly associated with direct radical scavenging activity, an alternative way to increase the antioxidant status of a cell is to enhance the endogenous (phase II) defense system consisting of cytoprotective antioxidant enzymes, including NAD(P)H:quinone oxidoreductase 1 (NQO1). These enzymes are transcriptionally regulated by the antioxidant response element (ARE) via the transcription factor Nrf2. Extracts derived from cultivated Ulva sp., a green alga regarded as a marine vegetable (sea lettuce), potently activated the Nrf2-ARE pathway in IMR-32 neuroblastoma and LNCaP prostate cancer cells. RNA interference studies demonstrated that Nrf2 and PI3 kinase are essential for the phase II response in IMR-32 cells. Activity-enriched fractions induced Nrf2 nuclear translocation and target gene transcription, and boosted the cellular glutathione level and therefore antioxidant status. A single-dose gavage feeding of Ulva-derived fractions increased Nqo1 transcript levels in various organs. Nqo1 induction spiked in different tissues, depending on the specific chemical composition of each administered fraction. We purified and characterized four ARE inducers in this extract, including loliolide (1), isololiolide (2), a megastigmen (3), and a novel chlorinated unsaturated aldehyde (4). The ARE-active fractions attenuated lipopolysaccharide-induced iNOS and Cox2 gene expression in macrophagic RAW264.7 cells, decreasing nitric oxide (NO) and prostaglandin E2 (PGE2) production, respectively. Nqo1 activity and NO production were abrogated in nrf2−/− mouse embryonic fibroblasts, providing a direct link between the induction of phase II response and anti-inflammatory activity. PMID:24005795

  18. Prevention of postoperative atrial fibrillation: novel and safe strategy based on the modulation of the antioxidant system

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    Ramón eRodrigo

    2012-04-01

    Full Text Available Postoperative atrial fibrillation (AF is the most common arrhythmia following cardiac surgery with extracorporeal circulation. The pathogenesis of postoperative AF is multifactorial. Oxidative stress, caused by the unavoidable ischemia-reperfusion event occurring in this setting, is a major contributory factor. ROS-derived effects could result in lipid peroxidation, protein carbonylation or DNA oxidation of cardiac tissue, thus leading to functional and structural myocardial remodeling. The vulnerability of myocardial tissue to the oxidative challenge is also dependent on the activity of the antioxidant system. High ROS levels, overwhelming this system, should result in deleterious cellular effects, such as the induction of necrosis, apoptosis or autophagy. Nevertheless, tissue exposure to low to moderate ROS levels could trigger a survival response with a trend to reinforce the antioxidant defense system. Administration of n-3 polyunsaturated fatty acids (PUFA, known to involve a moderate ROS production, is consistent with a diminished vulnerability to the development of postoperative AF. Accordingly, supplementation of n-3 PUFA successfully reduced the incidence of postoperative AF after coronary bypass grafting. This response is due to an up-regulation of antioxidant enzymes, as shown in experimental models. In turn, non-enzymatic antioxidant reinforcement through vitamin C administration prior to cardiac surgery has also reduced the postoperative AF incidence. Therefore, it should be expected that a mixed therapy result in an improvement of the cardioprotective effect by modulating both components of the antioxidant system. We present available evidence supporting the view of an effective prevention of postoperative AF including a 2-step therapeutic strategy: n-3 PUFA followed by vitamin C supplementation to patients scheduled for cardiac surgery with extracorporeal circulation. The present study should encourage the design of clinical

  19. Tissue Specificity of a Response of the Pro- and Antioxidative System After Resuscitation

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    A. G. Zhukova

    2005-01-01

    Full Text Available This investigation was undertaken to study the resistance of membrane structures and the level of the intracellular defense systems of the heart, brain, and liver in animals with active versus passive behavior in different periods (days 7 and 30 after resuscitation made 10 minutes following systemic circulatory arrest. All the animals in which systemic circulation had been stopped were survivors with the cession of neurological deficit. The activity of antioxidative defense enzymes, such as cata-lase and superoxide dismutase, in cardiac, cerebral, and hepatic tissues was assayed by spectrophotometry using the conventional methods. The level of stress-induced protein HSP70 was measured in the tissue cytosolic fraction by the Western blotting assay. The activity of Ca2+ transport in the myocardial sarcoplasmic reticulum was determined on an Orion EA 940 ionomer («Orion Research», USA having a Ca2+-selective electrode. The findings show a significant tissue specificity in different postresuscitative periods (days 7 and 30 and varying (protective to damaging cardiac, cerebral, and hepatic responses in active and passive animals to hypoxia.

  20. Influence of genotype, cultivation system and irrigation regime on antioxidant capacity and selected phenolics of blueberries (Vaccinium corymbosum L.).

    Science.gov (United States)

    Cardeñosa, Vanessa; Girones-Vilaplana, Amadeo; Muriel, José Luis; Moreno, Diego A; Moreno-Rojas, José M

    2016-07-01

    Demand for and availability of blueberries has increased substantially over recent years, driven in part by their health-promoting properties. Three blueberry varieties ('Rocío', V2, and V3) were grown under two cultivation systems (open-field and plastic tunnels) and subjected to two irrigations regimes (100% and 80% of crop evapotranspiration) in two consecutive years (2011-2012). They were evaluated for their phytochemical composition and antioxidant capacity. Genotype influenced the antioxidant capacity and the content of the three groups of phenolics in the blueberries. The antioxidant activity and total flavonols content increased when the blueberries were grown under open-field conditions. Deficit irrigation conditions led to additional positive effects on their phenolics (delphinidn-3-acetilhexoside content was increased under plastic tunnel with deficit irrigation). In conclusion, the amount of phenolic compounds and the antioxidant capacity of blueberries were not negatively affected by water restriction; Moreover, several changes were recorded due to growing system and genotype. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Abrus precatorius Leaves: Antioxidant Activity in Food and Biological Systems, pH, and Temperature Stability

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    Vanitha Reddy Palvai

    2014-01-01

    Full Text Available Natural antioxidants present in foods and other biological materials have attracted considerable interest because of their presumed safety and potential nutritional and therapeutic effects. Antioxidant constituents of plant materials act as radical scavengers and convert the radicals to less reactive species. Abrus precatorius (AP was analyzed for its proximate and phytochemical composition. The leaves were extracted with methanol (ME and analyzed for antioxidant activity by radical scavenging method, reducing power, ferric reducing capacity, and in vitro inhibition of Fenton’s reagent-induced oxidation in oil emulsion and microsomes. In addition, the effect of temperature (100∘C, 15, and 30 min and pH (4.5, 7, and 9 C on the antioxidant activity of ME was investigated. The leaves were rich in total polyphenols, flavonoids, β-carotene, glutathione, α-tocopherol, and ascorbic acid. The ME exhibited varying degree of antioxidant activity in a dose-dependent manner. The AP exhibited more inhibition of oxidation in microsomes (73% than compared to oil emulsion (21%. Heat treatment resulted in an increase of radical scavenging activity of extract (28% to 43%. At pH 4.5 the extract exhibited more antioxidant activity and stability compared to pH 7 and 9. Data indicates that potential exists for the utilization of Abrus precatorius as a natural antioxidant.

  2. Fluoxetine Prevents Oligodendrocyte Cell Death by Inhibiting Microglia Activation after Spinal Cord Injury

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    Lee, Jee Y.; Kang, So R.

    2015-01-01

    Abstract Oligodendrocyte cell death and axon demyelination after spinal cord injury (SCI) are known to be important secondary injuries contributing to permanent neurological disability. Thus, blocking oligodendrocyte cell death should be considered for therapeutic intervention after SCI. Here, we demonstrated that fluoxetine, an antidepressant drug, alleviates oligodendrocyte cell death by inhibiting microglia activation after SCI. After injury at the T9 level with a Precision Systems and Instrumentation (Lexington, KY) device, fluoxetine (10 mg/kg, intraperitoneal) was administered once a day for the indicated time points. Immunostaining with CD11b (OX-42) antibody and quantification analysis showed that microglia activation was significantly inhibited by fluoxetine at 5 days after injury. Fluoxetine also significantly inhibited activation of p38 mitogen-activated protein kinase (p38-MAPK) and expression of pro-nerve growth factor (pro-NGF), which is known to mediate oligodendrocyte cell death through the p75 neurotrophin receptor after SCI. In addition, fluoxetine attenuated activation of Ras homolog gene family member A and decreased the level of phosphorylated c-Jun and, ultimately, alleviated caspase-3 activation and significantly reduced cell death of oligodendrocytes at 5 days after SCI. Further, the decrease of myelin basic protein, myelin loss, and axon loss in white matter was also significantly blocked by fluoxetine, as compared to vehicle control. These results suggest that fluoxetine inhibits oligodendrocyte cell death by inhibiting microglia activation and p38-MAPK activation, followed by pro-NGF production after SCI, and provide a potential usage of fluoxetine for a therapeutic agent after acute SCI in humans. PMID:25366938

  3. Distinct spatial distribution of microglia and macrophages following mesenchymal stem cell implantation in mouse brain.

    Science.gov (United States)

    Le Blon, Debbie; Hoornaert, Chloé; Daans, Jasmijn; Santermans, Eva; Hens, Niel; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter

    2014-09-01

    Although implantation of cellular material in the central nervous system (CNS) is a key direction in CNS regenerative medicine, this approach is currently limited by the occurrence of strong endogenous immune cell responses. In a model of mesenchymal stem cell (MSC) grafting in the CNS of immune-competent mice, we previously described that MSC grafts become highly surrounded and invaded by Iba1(+) myeloid cells (microglia and/or macrophages). Here, following grafting of blue fluorescent protein (BFP)-expressing MSC in the CNS of CX3CR1(+/-) and CX3CR1(-/-) mice, our results indicate: (1) that the observed inflammatory response is independent of the fractalkine signalling axis, and (2) that a significant spatial distribution of Iba1(+) inflammatory cells occurs, in which Iba1(+) CX3CR1(+) myeloid cells mainly surround the MSC graft and Iba1(+) CX3CR1(-) myeloid cells mainly invade the graft at 10 days post transplantation. Although Iba1(+) CX3CR1(+) myeloid cells are considered to be of resident microglial origin, Iba1(+) CX3CR1(-) myeloid cells are most likely of peripheral monocyte/macrophage origin. In order to confirm the latter, we performed MSC-BFP grafting experiments in the CNS of eGFP(+) bone marrow chimeric C57BL/6 mice. Analysis of MSC-BFP grafts in the CNS of these mice confirmed our observation that peripheral monocytes/macrophages invade the MSC graft and that resident microglia surround the MSC graft site. Furthermore, analysis of major histocompatibility complex class II (MHCII) expression revealed that mainly macrophages, but not microglia, express this M1 pro-inflammatory marker in the context of MSC grafting in the CNS. These results again highlight the complexity of cell implantation immunology in the CNS.

  4. Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia

    OpenAIRE

    Wei, Li; Tokizane, Kyohei; Konishi, Hiroyuki; Yu, Hua-Rong; Kiyama, Hiroshi

    2017-01-01

    Background Several G-protein-coupled receptors (GPCRs) have been shown to be important signaling mediators between neurons and glia. In our previous screening for identification of nerve injury-associated GPCRs, G-protein-coupled receptor 84 (GPR84) mRNA showed the highest up-regulation by microglia after nerve injury. GPR84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model, yet its function in resident microglia in the central nervous system is poorly understood...

  5. Antioxidant activity stimulated by ultraviolet radiation in the nervous system of a crustacean

    International Nuclear Information System (INIS)

    Hollmann, Gabriela; Ferreira, Gabrielle de Jesus; Geihs, Márcio Alberto; Vargas, Marcelo Alves

    2015-01-01

    Highlights: • Ultraviolet (UV) radiation produces biological damage, principally oxidative stress. • We analyzed oxidative stress in the central nervous system (CNS) of a crab. • The damage was evaluated using biochemical tests and immunohistochemistry. • We verified the occurrence of apoptosis in the brain of the UV-exposed crabs. • Environmental doses of UV can cause oxidative damage to CNS, including apoptosis. - Abstract: Ultraviolet (UV) radiation can produce biological damage, principally oxidative stress, by increasing the production of reactive oxygen species (ROS). This study evaluated biochemical impairments related to the oxidative stress induced by UVA, UVB and UVA + UVB (solar simulator-SIM) in environmental doses, during five consecutive days of exposure, in the brain and eyestalk of the crab Ucides cordatus. We evaluated these regions by sampling on the 1st, 3rd and 5th days of UV exposure for lipid peroxidation (LPO), antioxidant capacity against the peroxyl radical (ACAP), and the activities of catalase (CAT), glutathione peroxidase (GPX) and glutathione-S-transferase (GST). Immunohistochemical and immunoblotting assays were performed for anti-activated-caspase 3 in the brains. After the first day of exposure, LPO increased in the eyestalks and brains of the UV-exposed animals; ACAP, and CAT, GPX and GST activities also increased in the brains. On the third day, the LPO values in the eyestalk remained high in the UV-exposed groups, while ACAP decreased in the brain and eyestalk and CAT activity remained high in all irradiated groups in both regions. On the fifth day, LPO decreased in the eyestalk and brain of the UV-exposed groups. These results may have been a consequence of the antioxidant defense system (ADS) activity, since CAT activity was high in both regions, ACAP was high in the eyestalks of the SIM group, and GPX activity remained high in the eyestalks of the UVA and UVB groups. Immunohistochemical assays and immunoblotting

  6. Antioxidant activity stimulated by ultraviolet radiation in the nervous system of a crustacean

    Energy Technology Data Exchange (ETDEWEB)

    Hollmann, Gabriela, E-mail: gabrielahollmann@biof.ufrj.br [Programa de Pós Graduação em Ciências Biológicas-Fisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro-UFRJ, Rio de Janeiro, RJ 21941-590 (Brazil); Ferreira, Gabrielle de Jesus, E-mail: gabi_ferreiira@hotmail.com [Programa de Pós Graduação em Ciências Biológicas-Fisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro-UFRJ, Rio de Janeiro, RJ 21941-590 (Brazil); Geihs, Márcio Alberto, E-mail: geihs@hotmail.com [Programa de Pós Graduação em Ciências Fisiológicas-Fisiologia Animal Comparada. Instituto de Ciências Biológicas, Universidade Federal do Rio Grande-FURG, Rio Grande, RS 96201-900 (Brazil); Vargas, Marcelo Alves, E-mail: biovargas@gmail.com [Programa de Pós Graduação em Ciências Fisiológicas-Fisiologia Animal Comparada. Instituto de Ciências Biológicas, Universidade Federal do Rio Grande-FURG, Rio Grande, RS 96201-900 (Brazil); and others

    2015-03-15

    Highlights: • Ultraviolet (UV) radiation produces biological damage, principally oxidative stress. • We analyzed oxidative stress in the central nervous system (CNS) of a crab. • The damage was evaluated using biochemical tests and immunohistochemistry. • We verified the occurrence of apoptosis in the brain of the UV-exposed crabs. • Environmental doses of UV can cause oxidative damage to CNS, including apoptosis. - Abstract: Ultraviolet (UV) radiation can produce biological damage, principally oxidative stress, by increasing the production of reactive oxygen species (ROS). This study evaluated biochemical impairments related to the oxidative stress induced by UVA, UVB and UVA + UVB (solar simulator-SIM) in environmental doses, during five consecutive days of exposure, in the brain and eyestalk of the crab Ucides cordatus. We evaluated these regions by sampling on the 1st, 3rd and 5th days of UV exposure for lipid peroxidation (LPO), antioxidant capacity against the peroxyl radical (ACAP), and the activities of catalase (CAT), glutathione peroxidase (GPX) and glutathione-S-transferase (GST). Immunohistochemical and immunoblotting assays were performed for anti-activated-caspase 3 in the brains. After the first day of exposure, LPO increased in the eyestalks and brains of the UV-exposed animals; ACAP, and CAT, GPX and GST activities also increased in the brains. On the third day, the LPO values in the eyestalk remained high in the UV-exposed groups, while ACAP decreased in the brain and eyestalk and CAT activity remained high in all irradiated groups in both regions. On the fifth day, LPO decreased in the eyestalk and brain of the UV-exposed groups. These results may have been a consequence of the antioxidant defense system (ADS) activity, since CAT activity was high in both regions, ACAP was high in the eyestalks of the SIM group, and GPX activity remained high in the eyestalks of the UVA and UVB groups. Immunohistochemical assays and immunoblotting

  7. Radioprotective action of beta-carotin and vitamin A, C and E complexes at reproductive system and indices of antioxidant system in male rat blood and liver

    International Nuclear Information System (INIS)

    Vereshchako, G.G.; Konoplya, E.F.; Khodosovskaya, A.M.; Rutkovskaya, Zh.A.

    2008-01-01

    Effects of total irradiation in low dose at the state of rat mail reproductive system, lipid peroxidation processes and antioxidant system in rat blood and liver tissues as well as radioprotective capacity of beta-carotin with vitamin A, C and E complexes were investigated. It was established that injection of this substances to rat's organism one day before irradiation in 1.0 Gy dose led to normalization of spermatogenic cells number, increase of nucleic acids content in testes and significant improvement of antioxidant status of blood and liver tissue. (authors)

  8. PVA/Dextran hydrogel patches as delivery system of antioxidant astaxanthin: a cardiovascular approach.

    Science.gov (United States)

    Zuluaga, M; Gregnanin, G; Cencetti, C; Di Meo, C; Gueguen, V; Letourneur, D; Meddahi-Pellé, A; Pavon-Djavid, G; Matricardi, P

    2017-12-28

    After myocardial infarction, the heart's mechanical properties and its intrinsic capability to recover are compromised. To improve this recovery, several groups have developed cardiac patches based on different biomaterials strategies. Here, we developed polyvinylalcohol/dextran (PVA/Dex) elastic hydrogel patches, obtained through the freeze thawing (FT) process, with the aim to deliver locally a potent natural antioxidant molecule, astaxanthin, and to assist the heart's response against the generated myofibril stress. Extensive rheological and dynamo-mechanical characterization of the effect of the PVA molecular weight, number of freeze-thawing cycles and Dex addition on the mechanical properties of the resulting hydrogels, were carried out. Hydrogel systems based on PVA 145 kDa and PVA 47 kDa blended with Dex 40 kDa, were chosen as the most promising candidates for this application. In order to improve astaxanthin solubility, an inclusion system using hydroxypropyl-β-cyclodextrin was prepared. This system was posteriorly loaded within the PVA/Dex hydrogels. PVA145/Dex 1FT and PVA47/Dex 3FT showed the best rheological and mechanical properties when compared to the other studied systems; environmental scanning electron microscope and confocal imaging evidenced a porous structure of the hydrogels allowing astaxanthin release. In vitro cellular behavior was analyzed after 24 h of contact with astaxanthin-loaded hydrogels. In vivo subcutaneous biocompatibility was performed in rats using PVA145/Dex 1FT, as the best compromise between mechanical support and astaxanthin delivery. Finally, ex vivo and in vivo experiments showed good mechanical and compatibility properties of this hydrogel. The obtained results showed that the studied materials have a potential to be used as myocardial patches to assist infarcted heart mechanical function and to reduce oxidative stress by the in situ release of astaxanthin.

  9. The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Robert E. Smith

    2016-11-01

    Full Text Available It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However, many antioxidants behave quite differently in vivo. Some of them, such as resveratrol (in red wine and epigallocatechin gallate or EGCG (in green tea can activate the nuclear erythroid-2 like factor-2 (Nrf2 transcription factor. It is a master regulator of endogenous cellular defense mechanisms. Nrf2 controls the expression of many antioxidant and detoxification genes, by binding to antioxidant response elements (AREs that are commonly found in the promoter region of antioxidant (and other genes, and that control expression of those genes. The mechanisms by which Nrf2 relieves oxidative stress and limits cardiac injury as well as the progression to heart failure are described. Also, the ability of statins to induce Nrf2 in the heart, brain, lung, and liver is mentioned. However, there is a negative side of Nrf2. When over-activated, it can cause (not prevent cardiovascular diseases and multi-drug resistance cancer.

  10. Effect of balneotherapy on the antioxidant system--a controlled pilot study.

    Science.gov (United States)

    Bender, Tamás; Bariska, János; Vághy, Richárd; Gomez, Roberto; Imre Kovács

    2007-01-01

    Balneotherapy is among the most widely used modalities of physical therapy in countries rich in mineral waters. This trial was intended to ascertain whether balneotherapy (i.e., therapeutic bath in mineral water) has any influence on the antioxidant system and whether there are any differences compared to bathing in tap water. The ten subjects in Group I bathed in alkaline thermal water, Group II used alkaline, chlorine-containing mineral water, whereas Group III bathed in tap water. Catalase, superoxide dismutase, malondialdehyde protein and glutathione peroxidase levels were measured at baseline and after concluding the course of balneotherapy. Balneotherapy with either of the two mineral waters reduced the activity of all four enzymes studied. Using tap water, however, had no influence on either catalase or superoxide dismutase activity after one session or glutathione peroxidase levels after a course of ten balneotherapy treatments. Thermal water may have a beneficial effect on the formation of free radicals. The therapeutic efficacy of mineral vs. tap water is different, although bathing in hot water itself reduces enzyme activity.

  11. Eucalyptus tolerance mechanisms to lanthanum and cerium: subcellular distribution, antioxidant system and thiol pools.

    Science.gov (United States)

    Shen, Yichang; Zhang, Shirong; Li, Sen; Xu, Xiaoxun; Jia, Yongxia; Gong, Guoshu

    2014-12-01

    Guanglin 9 (Eucalyptus grandis × Eucalyptus urophlla) and Eucalyptus grandis 5 are two eucalyptus species which have been found to grow normally in soils contaminated with lanthanum and cerium, but the tolerance mechanisms are not clear yet. In this study, a pot experiment was conducted to investigate the tolerance mechanisms of the eucalyptus to lanthanum and cerium. Cell walls stored 45.40-63.44% of the metals under lanthanum or cerium stress. Peroxidase and catalase activities enhanced with increasing soil La or Ce concentrations up to 200 mg kg(-1), while there were no obvious changes in glutathione and ascorbate concentrations. Non-protein thiols concentrations increased with increasing treatment levels up to 200 mg kg(-1), and then decreased. Phytochelatins concentrations continued to increase under La or Ce stress. Therefore, the two eucalyptus species are La and Ce tolerant plants, and the tolerance mechanisms include cell wall deposition, antioxidant system response, and thiol compound synthesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Effects of lead on tolerance, bioaccumulation, and antioxidative defense system of green algae, Cladophora.

    Science.gov (United States)

    Cao, De-ju; Shi, Xiao-dong; Li, Hao; Xie, Pan-pan; Zhang, Hui-min; Deng, Juan-wei; Liang, Yue-gan

    2015-02-01

    Effects of various concentrations (0.5, 1.0, 2.5, 5.0, 7.5, and 10.0 mg/L) of lead (Pb(2+)) on the growth, bioaccumulation, and antioxidative defense system of green algae, Cladophora, was investigated. Low concentrations of Pb(2+) accelerated Cladophora growth, but concentrations of 10.0 mg/L and above inhibited the growth because of the hinderance to photosynthesis. The total soluble sugar content of Cladophora was affected by Pb(2+) treatment, but the protein content showed no significant changes. The malondialdehyde (MDA) content and peroxidase(POD) activity of Cladophora gradually increased whereas superoxide dismutase(SOD) decreased with Pb(2+) concentrations. Catalase (CAT) activity exhibited no significant changes following Pb(2+) treatment. Pb(2+) accumulated in Cladophora and that the lead content in Cladophora was correlated with POD growth, MDA, and Metallothionein (MT). POD and MT play a role in the survival of Cladophora in Pb-contaminated environments. This study suggests that Cladophora can be a choice organism for the phytoremediation of Pb-polluted coastal areas. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. In vitro modeling of HIV proviral activity in microglia.

    Science.gov (United States)

    Campbell, Lee A; Richie, Christopher T; Zhang, Yajun; Heathward, Emily J; Coke, Lamarque M; Park, Emily Y; Harvey, Brandon K

    2017-12-01

    Microglia, the resident macrophages of the brain, play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND) due to their productive infection by HIV. This results in the release of neurotoxic viral proteins and pro-inflammatory compounds which negatively affect the functionality of surrounding neurons. Because models of HIV infection within the brain are limited, we aimed to create a novel microglia cell line with an integrated HIV provirus capable of recreating several hallmarks of HIV infection. We utilized clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology and integrated a modified HIV provirus into CHME-5 immortalized microglia to create HIV-NanoLuc CHME-5. In the modified provirus, the Gag-Pol region is replaced with the coding region for NanoLuciferase (NanoLuc), which allows for the rapid assay of HIV long terminal repeat activity using a luminescent substrate, while still containing the necessary genetic material to produce established neurotoxic viral proteins (e.g. tat, nef, gp120). We confirmed that HIV-NanoLuc CHME-5 microglia express NanoLuc, along with the HIV viral protein Nef. We subsequently exposed these cells to a battery of experiments to modulate the activity of the provirus. Proviral activity was enhanced by treating the cells with pro-inflammatory factors lipopolysaccharide (LPS) and tumor necrosis factor alpha and by overexpressing the viral regulatory protein Tat. Conversely, genetic modification of the toll-like receptor-4 gene by CRISPR/Cas9 reduced LPS-mediated proviral activation, and pharmacological application of NF-κB inhibitor sulfasalazine similarly diminished proviral activity. Overall, these data suggest that HIV-NanoLuc CHME-5 may be a useful tool in the study of HIV-mediated neuropathology and proviral regulation. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  14. Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia.

    Science.gov (United States)

    Wei, Li; Tokizane, Kyohei; Konishi, Hiroyuki; Yu, Hua-Rong; Kiyama, Hiroshi

    2017-10-03

    Several G-protein-coupled receptors (GPCRs) have been shown to be important signaling mediators between neurons and glia. In our previous screening for identification of nerve injury-associated GPCRs, G-protein-coupled receptor 84 (GPR84) mRNA showed the highest up-regulation by microglia after nerve injury. GPR84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model, yet its function in resident microglia in the central nervous system is poorly understood. We used endogenous, natural, and surrogate agonists for GPR84 (capric acid, embelin, and 6-OAU, respectively) and examined their effect on mouse primary cultured microglia in vitro. 6-n-Octylaminouracil (6-OAU), embelin, and capric acid rapidly induced membrane ruffling and motility in cultured microglia obtained from C57BL/6 mice, although these agonists failed to promote microglial pro-inflammatory cytokine expression. Concomitantly, 6-OAU suppressed forskolin-induced increase of cAMP in cultured microglia. Pertussis toxin, an inhibitor of Gi-coupled signaling, completely suppressed 6-OAU-induced microglial membrane ruffling and motility. In contrast, no 6-OAU-induced microglial membrane ruffling and motility was observed in microglia from DBA/2 mice, a mouse strain that does not express functional GPR84 protein due to endogenous nonsense mutation of the GPR84 gene. GPR84 mediated signaling causes microglial motility and membrane ruffling but does not promote pro-inflammatory responses. As GPR84 is a known receptor for medium-chain fatty acids, those released from damaged brain cells may be involved in the enhancement of microglial motility through GPR84 after neuronal injury.

  15. Biochemical and molecular characterization of the antioxidative system of Coffea sp. under cold conditions in genotypes with contrasting tolerance.

    Science.gov (United States)

    Fortunato, Ana S; Lidon, Fernando C; Batista-Santos, Paula; Leitão, António Eduardo; Pais, Isabel P; Ribeiro, Ana I; Ramalho, José Cochicho

    2010-03-15

    Low positive temperature (chilling) is frequently linked to the promotion of oxidative stress conditions, and is of particular importance in the coffee plant due to its severe impact on growth, development, photosynthesis and production. Nevertheless, some acclimation ability has been reported within the Coffea genus, and is possibly related to oxidative stress control. Using an integrated biochemical and molecular approach, the characterization of the antioxidative system of genotypes with different cold acclimation abilities was performed. Experiments were carried out using 1.5-year-old coffee seedlings of Coffea canephora cv. Apoatã, C. arabica cv. Catuaí, C. dewevrei and 2 hybrids, Icatu (C. arabicaxC. canephora) and Piatã (C. dewevreixC. arabica) subjected to a gradual cold treatment and a recovery period. Icatu showed the greatest ability to control oxidative stress, as reflected by the enhancement of several antioxidative components (Cu,Zn-SOD and APX activities; ascorbate, alpha-tocopherol and chlorogenic acids (CGAs) contents) and lower reactive oxygen species contents (H(2)O(2) and OH). Gene expression studies show that GRed, DHAR and class III and IV chitinases might also be involved in the cold acclimation ability of Icatu. Catuaí showed intermediate acclimation ability through the reinforcement of some antioxidative molecules, usually to a lesser extent than that observed in Icatu. On the other hand, C. dewevrei showed the poorest response in terms of antioxidant accumulation, and also showed the greatest increase in OH values. The difference in the triggering of antioxidative traits supports the hypothesis of its importance to cold (and photoinhibition) tolerance in Coffea sp. and could provide a useful probe to identify tolerant genotypes. Copyright 2009 Elsevier GmbH. All rights reserved.

  16. Evaluation of polyphenolic content and antioxidant activity in two onion varieties grown under organic and conventional production systems.

    Science.gov (United States)

    Ren, Feiyue; Reilly, Kim; Gaffney, Michael; Kerry, Joseph P; Hossain, Mohammad; Rai, Dilip K

    2017-07-01

    Onions contain a number of bioactive compounds, in particular polyphenols. They are rich sources of such compounds in the human diet and offer significant health benefits to the consumer. Demand for organic crops is steadily increasing partly based on the expected health benefits of organic food consumption. The current study examines the influence of organic and conventional crop management practices on bioactive polyphenolic content of onion. We examined the effect of conventional, organic, and mixed cultivation practices on the content of total phenolics, total flavonoids and antioxidant activity in two varieties of onion grown over 4 years in a split-plot factorial systems comparison trial. Levels of total phenolics and total flavonoids showed a significant year-on-year variation and were significantly different between organic and conventional production systems. The levels of total phenolics, total flavonoids and antioxidant activity in general were significantly higher (P onion. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  17. Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1β, BDNF and synaptic plasticity.

    Science.gov (United States)

    Patterson, Susan L

    2015-09-01

    Older individuals often experience declines in cognitive function after events (e.g. infection, or injury) that trigger activation of the immune system. This occurs at least in part because aging sensitizes the response of microglia (the brain's resident immune cells) to signals triggered by an immune challenge. In the aging brain, microglia respond to these signals by producing more pro-inflammatory cytokines (e.g. interleukin-1beta or IL-1β) and producing them for longer than microglia in younger brains. This exaggerated inflammatory response can compromise processes critical for optimal cognitive functioning. Interleukin-1β is central to the inflammatory response and is a key mediator and modulator of an array of associated biological functions; thus its production and release is usually very tightly regulated. This review will focus on the impact of dysregulated production of IL-1β on hippocampus dependent-memory systems and associated synaptic plasticity processes. The neurotrophin brain-derived neurotrophic factor (BNDF) helps to protect neurons from damage caused by infection or injury, and it plays a critical role in many of the same memory and hippocampal plasticity processes compromised by dysregulated production of IL-1β. This suggests that an exaggerated brain inflammatory response, arising from aging and a secondary immune challenge, may erode the capacity to provide the BDNF needed for memory-related plasticity processes at hippocampal synapses. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Camel milk protein hydrolysates with improved technofunctional properties and enhanced antioxidant potential in in vitro and in food model systems.

    Science.gov (United States)

    Al-Shamsi, Kholoud Awad; Mudgil, Priti; Hassan, Hassan Mohamed; Maqsood, Sajid

    2018-01-01

    Camel milk protein hydrolysates (CMPH) were generated using proteolytic enzymes, such as alcalase, bromelain, and papain, to explore the effect on the technofunctional properties and antioxidant potential under in vitro and in real food model systems. Characterization of the CMPH via degree of hydrolysis, sodium dodecyl sulfate-PAGE, and HPLC revealed that different proteins in camel milk underwent degradation at different degrees after enzymatic hydrolysis using 3 different enzymes for 2, 4, and 6 h, with papain displaying the highest degradation. Technofunctional properties, such as emulsifying activity index, surface hydrophobicity, and protein solubility, were higher in CMPH than unhydrolyzed camel milk proteins. However, the water and fat absorption capacity were lower in CMPH compared with unhydrolyzed camel milk proteins. Antioxidant properties as assessed by 2,2-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging activities and metal-chelating activity were enhanced after hydrolysis, in contrast to ferric-reducing antioxidant power which showed a decrease after hydrolysis. The CMPH were also tested in real food model systems for their potential to inhibit lipid peroxidation in fish mince and grape seed oil-in-water emulsion, and we found that papain-produced hydrolysate displayed higher inhibition than alcalase- and bromelain-produced hydrolysates. Therefore, the CMPH demonstrated effective antioxidant potential in vitro as well as in real food systems and showed enhanced functional properties, which guarantees their potential applications in functional foods. The present study is one of few reports available on CMPH being explored in vitro as well as in real food model systems. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Heterogeneous role of the glutathione antioxidant system in modulating the response of ESFT to fenretinide in normoxia and hypoxia.

    Directory of Open Access Journals (Sweden)

    Tapiwanashe Magwere

    Full Text Available Glutathione (GSH is implicated in drug resistance mechanisms of several cancers and is a key regulator of cell death pathways within cells. We studied Ewing's sarcoma family of tumours (ESFT cell lines and three mechanistically distinct anticancer agents (fenretinide, doxorubicin, and vincristine to investigate whether the GSH antioxidant system is involved in the reduced sensitivity to these chemotherapeutic agents in hypoxia. Cell viability and death were assessed by the trypan blue exclusion assay and annexin V-PI staining, respectively. Hypoxia significantly decreased the sensitivity of all ESFT cell lines to fenretinide-induced death, whereas the effect of doxorubicin or vincristine was marginal and cell-line-specific. The response of the GSH antioxidant system in ESFT cell lines to hypoxia was variable and also cell-line-specific, although the level of GSH appeared to be most dependent on de novo biosynthesis rather than recycling. RNAi-mediated knockdown of key GSH regulatory enzymes γ-glutamylcysteine synthetase or glutathione disulfide reductase partially reversed the hypoxia-induced resistance to fenretinide, and increasing GSH levels using N-acetylcysteine augmented the hypoxia-induced resistance in a cell line-specific manner. These observations are consistent with the conclusion that the role of the GSH antioxidant system in modulating the sensitivity of ESFT cells to fenretinide is heterogeneous depending on environment and cell type. This is likely to limit the value of targeting GSH as a therapeutic strategy to overcome hypoxia-induced drug resistance in ESFT. Whether targeting the GSH antioxidant system in conjunction with other therapeutics may benefit some patients with ESFT remains to be seen.

  20. ATP Modifies the Proteome of Extracellular Vesicles Released by Microglia and Influences Their Action on Astrocytes

    Directory of Open Access Journals (Sweden)

    Francesco Drago

    2017-12-01

    Full Text Available Extracellular ATP is among molecules promoting microglia activation and inducing the release of extracellular vesicles (EVs, which are potent mediators of intercellular communication between microglia and the microenvironment. We previously showed that EVs produced under ATP stimulation (ATP-EVs propagate a robust inflammatory reaction among astrocytes and microglia in vitro and in mice with subclinical neuroinflammation (Verderio et al., 2012. However, the proteome of EVs released upon ATP stimulation has not yet been elucidated. In this study we applied a label free proteomic approach to characterize the proteome of EVs released constitutively and during microglia activation with ATP. We show that ATP drives sorting in EVs of a set of proteins implicated in cell adhesion/extracellular matrix organization, autophagy-lysosomal pathway and cellular metabolism, that may influence the response of recipient astrocytes to EVs. These data provide new clues to molecular mechanisms involved in microglia response to ATP and in microglia signaling to the environment via EVs.

  1. Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lu; Gallagher, Evan P., E-mail: evang3@uw.edu

    2013-01-15

    Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidative stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function. -- Highlights: ► Oxidative stress is an important mechanism of Cd-mediated olfactory injury. ► Cd induces antioxidant gene expression in the zebrafish olfactory system. ► The

  2. Strain-Related Differences on Response of Liver and Kidney Antioxidant Defense System in Two Rat Strains Following Diazinon Exposure

    Directory of Open Access Journals (Sweden)

    Maryam Salehi

    2016-02-01

    Full Text Available Background Diazinon (DZN is one of the most organophosphates that widely used in agriculture and ectoparasiticide formulations. Its extensive use as an effective pesticide was associated with the environmental deleterious effects on biological systems. Objectives The aim of this study was to investigate the potency of DZN to affect serum biochemical parameters and the antioxidant defense system in the liver and kidney of two rat strains. Materials and Methods In this experimental study, 30 female Wistar and 30 female Norway rats were randomly divided into control and DZN groups. DZN group was divided into four subgroups: 25, 50, 100 and 200 mg/kg of DZN administered groups by i.p. injection. The parameters were evaluated after 24 hours. Results At higher doses of DZN, superoxide dismutase, catalase, glutathione S-transferase and lactate dehydrogenase activities and glutathione (GSH and malondialdehyde levels in liver and kidney of Wistar rats were higher than Norway rats. At these concentrations, DZN increased some serum biochemical indices such as liver enzymes activities and levels of urea, uric acid and creatinine in Wistar rat. Conclusions DZN at higher doses alters the oxidant-antioxidant balance in liver and kidney of both rat strains and induces oxidative stress, which is associated with a depletion of GSH and increased lipid peroxidation. However, Wistar rats are found to be more sensitive to the toxicity of DZN compared to Norway rats. In addition, the effect of DZN on liver antioxidant system was more than kidney.

  3. Modulatory role of allopurinol on xanthine oxidoreductase system and antioxidant status in irradiated rats

    International Nuclear Information System (INIS)

    Zahran, A.M.; Azab, Kh.Sh.; Abbady, M.I.

    2006-01-01

    Allopurinol is a xanthine oxidase (XO) inhibitor, used for management of hyperuricaema. It acts on purine catabolism without disrupting the biosynthesis of purine. The present work was conducted to examine the role of xanthine oxidase inhibitor (allopurinol) in minimizing radiation injuries in male albino rats. Allopurinol was given to rats via intraperitoneal (i.p) injection at a dose of 30 mg/kg body wt/day for 7 successive days before starting irradiation and 14 successive days during and in between exposure to gamma radiation. Rats were exposed to whole body gamma radiation, delivered as 1 Gy every other day up to total dose 8 Gy. Results demonstrate that treatment with allopurinol by the regime assumed in the present study minimized significantly the amount of thiobarbituric acid reactive substances (TBARS), product of lipid peroxidation, in liver, intestine and plasma. This effect was associated with significant amelioration in xanthine oxidoreductase (XOR) system as observed on the 1st and 7th days post last radiation fraction. The severity of changes in antioxidant parameters namely: superoxide dismutase (SOD), Catalase (CAT) and reduced glutathione (GSH) were less manifested in liver, intestine and blood as compared to irradiated rats. The levels of nitric oxide (NO) were significantly improved in plasma and the two investigated tissues as compared to irradiated rats. A significant decrease in plasma uric acid concentration was recorded on the 1st and 7th days post last allopurinol dose. However, significant amelioration was recorded in the plasma uric acid of rats treated with allopurinol before and during radiation exposure as compared to irradiated rats. Accordingly, it could be concluded that XO inhibitor (allopurinol) play a significant role in minimizing the tissue damages upon exposure to ionizing radiation via preventing the over production of reactive oxygen species (ROS) in irradiated cells through the XOR system of irradiation rats

  4. Microglia change from a reactive to an age-like phenotype with the time in culture

    Science.gov (United States)

    Caldeira, Cláudia; Oliveira, Ana F.; Cunha, Carolina; Vaz, Ana R.; Falcão, Ana S.; Fernandes, Adelaide; Brites, Dora

    2014-01-01

    Age-related neurodegenerative diseases have been associated with chronic neuroinflammation and microglia activation. However, cumulative evidence supports that inflammation only occurs at an early stage once microglia change the endogenous characteristics with aging and switch to irresponsive/senescent and dystrophic phenotypes with disease progression. Thus, it will be important to have the means to assess the role of reactive and aged microglia when studying advanced brain neurodegeneration processes and age-associated related disorders. Yet, most studies are done with microglia from neonates since there are no adequate means to isolate degenerating microglia for experimentation. Indeed, only a few studies report microglia isolation from aged animals, using either short-term cultures or high concentrations of mitogens in the medium, which trigger microglia reactivity. The purpose of this study was to develop an experimental process to naturally age microglia after isolation from neonatal mice and to characterize the cultured cells at 2 days in vitro (DIV), 10 DIV, and 16 DIV. We found that 2 DIV (young) microglia had predominant amoeboid morphology and markers of stressed/reactive phenotype. In contrast, 16 DIV (aged) microglia evidenced ramified morphology and increased matrix metalloproteinase (MMP)-2 activation, as well as reduced MMP-9, glutamate release and nuclear factor kappa-B activation, in parallel with decreased expression of Toll-like receptor (TLR)-2 and TLR-4, capacity to migrate and phagocytose. These findings together with the reduced expression of microRNA (miR)-124, and miR-155, decreased autophagy, enhanced senescence associated beta-galactosidase activity and elevated miR-146a expression, are suggestive that 16 DIV cells mainly correspond to irresponsive/senescent microglia. Data indicate that the model represent an opportunity to understand and control microglial aging, as well as to explore strategies to recover microglia surveillance

  5. Costunolide inhibits proinflammatory cytokines and iNOS in activated murine BV2 microglia.

    Science.gov (United States)

    Rayan, Nirmala Arul; Baby, Nimmi; Pitchai, Daisy; Indraswari, Fransisca; Ling, Eng-Ang; Lu, Jia; Dheen, Thameem

    2011-06-01

    Costunolide, a sesquiterpene lactone present in Costus speciosus root exerts a variety of pharmacological activity but its effects on neuroinflammation have not been studied. Microglia, the resident phagocytic cells in the central nervous system respond to neuroinflammation and their overwhelming response in turn aggravate brain damage during infection, ischemia and neurodegenerative diseases. In this study, we report the effect of Costunolide on the production of proinflammatory mediators and mechanisms involved in BV2 microglial cells stimulated with LPS. Costunolide attenuated the expression of tumour necrosis factor-alpha, interleukin-1,6, inducible nitric oxide synthase, monocyte chemotactic protein 1 and cyclooxygenase 2 in activated microglia. This Costunolide-mediated inhibition was correspondent with the inhibition of NFkappaB activation. It has been further shown that Costunolide suppressed MAPK pathway activation by inducing MKP-1 production. Collectively our results suggest that Costunolide shows an ability to inhibit expression of multiple neuroinflammatory mediators and this is attributable to the compounds inhibition of NFkappaB and MAPK activation. This novel role of Costunolide upon investigation may aid in developing better therapeutic strategies for treatment of neuroinflammatory diseases.

  6. Visfatin Triggers Anorexia and Body Weight Loss through Regulating the Inflammatory Response in the Hypothalamic Microglia

    Directory of Open Access Journals (Sweden)

    Thai Hien Tu

    2017-01-01

    Full Text Available Visfatin is an adipokine that is secreted from adipose tissue, and it is involved in a variety of physiological processes. In particular, visfatin has been implicated in metabolic diseases, such as obesity and type 2 diabetes, which are directly linked to systemic inflammation. However, the potential impacts of visfatin on the hypothalamic control of energy homeostasis, which is involved in microglial inflammation, have not fully been investigated. In this study, we found that treatment with exogenous recombinant visfatin protein led to the activation of the inflammatory response in a microglial cell line. In addition, we observed that central administration of visfatin led to the activation of microglia in the hypothalamus. Finally, we found that visfatin reduced food intake and body weight through activating POMC neurons in association with microglia activation in mice. These findings indicate that elevation of central visfatin levels may be associated with homeostatic feeding behavior in response to metabolic shifts, such as increased adiposity following inflammatory processes in the hypothalamus.

  7. The spider effect: morphological and orienting classification of microglia in response to stimuli in vivo.

    Directory of Open Access Journals (Sweden)

    Rahul A Jonas

    Full Text Available The different morphological stages of microglial activation have not yet been described in detail. We transected the olfactory bulb of rats and examined the activation of the microglial system histologically. Six stages of bidirectional microglial activation (A and deactivation (R were observed: from stage 1A to 6A, the cell body size increased, the cell process number decreased, and the cell processes retracted and thickened, orienting toward the direction of the injury site; until stage 6A, when all processes disappeared. In contrast, in deactivation stages 6R to 1R, the microglia returned to the original site exhibiting a stepwise retransformation to the original morphology. Thin highly branched processes re-formed in stage 1R, similar to those in stage 1A. This reverse transformation mirrored the forward transformation except in stages 6R to 1R: cells showed multiple nuclei which were slowly absorbed. Our findings support a morphologically defined stepwise activation and deactivation of microglia cells.

  8. Fermented wheat powder induces the antioxidant and detoxifying system in primary rat hepatocytes.

    Science.gov (United States)

    La Marca, Margherita; Beffy, Pascale; Pugliese, Annalisa; Longo, Vincenzo

    2013-01-01

    Many plants exhibit antioxidant properties which may be useful in the prevention of oxidative stress reactions, such as those mediated by the formation of free radical species in different pathological situations. In recent years a number of studies have shown that whole grain products in particular have strong antioxidant activity. Primary cultures of rat hepatocytes were used to investigate whether and how a fermented powder of wheat (Lisosan G) is able to modulate antioxidant and detoxifying enzymes, and whether or not it can activate Nrf2 transcription factor or inhibit NF-kB activation. All of the antioxidant and detoxifying enzymes studied were significantly up-regulated by 0.7 mg/ml Lisosan G treatment. In particular, quinone oxidoreductase and heme oxygenase-1 were induced, although to different degrees, at the transcriptional, protein and/or activity levels by the treatment. As for the Nrf2 transcription factor, a partial translocation of its protein from the cytosol to the nucleus after 1 h of Lisosan G treatment was revealed by immunoblotting. Lisosan G was also observed to decrease H2O2-induced toxicity Taken together, these results show that this powder of wheat is an effective inducer of ARE/Nrf2-regulated antioxidant and detoxifying genes and has the potential to inhibit the translocation of NF-kB into the nucleus.

  9. Effect of modified atmosphere packaging (MAP) with low and superatmospheric oxygen on the quality and antioxidant enzyme system of golden needle mushrooms (Flammulina velutipes) during postharvest storage

    NARCIS (Netherlands)

    Wang, Cheng T.; Wang, Chang T.; Cao, Y.P.; Nout, M.J.R.; Sun, B.G.; Liu, L.

    2011-01-01

    To quantify the effect of oxygen concentrations on the quality and antioxidant enzyme system of stored golden needle mushroom, modified atmosphere packaging (MAP) with low and initial superatmospheric oxygen was applied during mushroom storage, and physiological changes associated with postharvest

  10. Toxic effects of boron on growth and antioxidant system parameters of maize (Zea mays L.) roots.

    Science.gov (United States)

    Esim, Nevzat; Tiryaki, Deniz; Karadagoglu, Omer; Atici, Okkes

    2013-10-01

    The aim of this study was to investigate the possible oxidative stress and the antioxidant response, which were caused on maize by boron (B). For this, 11- and 15-day-old maize seedlings were subjected to 2 or 4 mM B in the form of boric acid (H₃BO₃) for 2 and/or 6 days. At the end of the treatment period, root length, hydrogen peroxide (H₂O₂) content, malondialdehyde (MDA) content and the antioxidant enzymes superoxide dismutase (SOD), peroxidase (POX) and catalase (CAT) were measured. The results revealed that root length of plants, activity of antioxidative enzymes such as SOD, POX and CAT and also H₂O₂ contents and MDA levels were seriously affected by excess B. These results suggested that the oxidative stress occurred due to the toxic effect of B.

  11. Lithium limits trimethyltin-induced cytotoxicity and proinflammatory response in microglia without affecting the concurrent autophagy impairment.

    Science.gov (United States)

    Fabrizi, Cinzia; Pompili, Elena; Somma, Francesca; De Vito, Stefania; Ciraci, Viviana; Artico, Marco; Lenzi, Paola; Fornai, Francesco; Fumagalli, Lorenzo

    2017-02-01

    Trimethyltin (TMT) is a highly toxic molecule present as an environmental contaminant causing neurodegeneration particularly of the limbic system both in humans and in rodents. We recently described the occurrence of impairment in the late stages of autophagy in TMT-intoxicated astrocytes. Here we show that similarly to astrocytes also in microglia, TMT induces the precocious block of autophagy indicated by the accumulation of the autophagosome marker, microtubule associated protein light chain 3. Consistent with autophagy impairment we observe in TMT-treated microglia the accumulation of p62/SQSTM1, a protein specifically degraded through this pathway. Lithium has been proved effective in limiting neurodegenerations and, in particular, in ameliorating symptoms of TMT intoxication in rodents. In our in vitro model, lithium displays a pro-survival and anti-inflammatory action reducing both cell death and the proinflammatory response of TMT-treated microglia. In particular, lithium exerts these activities without reducing TMT-induced accumulation of light chain 3 protein. In fact, the autophagic block imposed by TMT is unaffected by lithium administration. These results are of interest as defects in the execution of autophagy are frequently observed in neurodegenerative diseases and lithium is considered a promising therapeutic agent for these pathologies. Thus, it is relevant that this cation can still maintain its pro-survival and anti-inflammatory role in conditions of autophagy block. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Inhibition of nitric oxide synthase expression in activated microglia and peroxynitrite scavenging activity by Opuntia ficus indica var. saboten.

    Science.gov (United States)

    Lee, Ming Hong; Kim, Jae Yeon; Yoon, Jeong Hoon; Lim, Hyo Jin; Kim, Tae Hee; Jin, Changbae; Kwak, Wie-Jong; Han, Chang-Kyun; Ryu, Jae-Ha

    2006-09-01

    Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO-), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. A butanol fraction obtained from 50% ethanol extracts of Opuntia ficus indica var. saboten (Cactaceae) stem (SK OFB901) and its hydrolysis product (SK OFB901H) inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC50 15.9, 4.2 microg/mL, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at higher than 30 microg/mL as observed by western blot analysis and RT-PCR experiment. They also inhibited the degradation of I-kappaB-alpha in activated microglia. Moreover, they showed strong activity of peroxynitrite scavenging in a cell free bioassay system. These results imply that Opuntia ficus indica may have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity. Copyright (c) 2006 John Wiley & Sons, Ltd.

  13. Involvement of an antioxidant defense system in the adaptive response to cadmium in maize seedlings (Zea mays L.).

    Science.gov (United States)

    Xu, Xianghua; Liu, Cuiying; Zhao, Xiaoyan; Li, Renying; Deng, Wenjing

    2014-11-01

    Chemical and biological analyses were used to investigate the growth response and antioxidant defense mechanism of maize seedlings (Zea mays L.) grown in soils with 0-100 mg kg(-1) Cd. Results showed that maize seedlings have strong abilities to accumulate and tolerate high concentrations of Cd. For soil with 50 mg kg(-1) Cd, the Cd contents in roots and shoots of maize seedlings are as large as 295.6 and 153.0 mg kg(-1) DW, respectively, without visible symptoms of toxicity. Lower soil Cd concentrations lead to a decrease in reduced glutathione (GSH) content in leaves of maize seedlings, whereas higher soil Cd concentrations resulted in an increase in the activities of superoxide dismutase, guaiacol peroxidase, catalase, and ascorbate peroxidase. Maize seedlings have strong capacities to adapt to low concentrations of Cd by consuming GSH and to develop an antioxidative enzyme system to defend against high-Cd stress.

  14. Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes

    DEFF Research Database (Denmark)

    Scheede-Bergdahl, Celena; Penkowa, Milena; Hidalgo, Juan

    2005-01-01

    lower levels of MT-I+II were also detected in the plasma of type 2 diabetic subjects compared with control subjects. These results suggest that, in control subjects, the MT-I+II defense system is active and inducible within skeletal muscle tissue and plasma. In type 2 diabetes, reduced levels of MT......Oxidative stress is implicated in diabetes complications, during which endogenous antioxidant defenses have important pathophysiological consequences. To date, the significance of endogenous antioxidants such as metallothioneins I and II (MT-I+II) in type 2 diabetes remains unclear. To examine....... Immunohistochemical analysis revealed reduced MT-I+II levels in the skeletal muscle of type 2 diabetic subjects compared with control subjects. Control subjects produced a robust increase of MT-I+II in response to training; however, in type 2 diabetes, MT-I+II levels remained essentially unchanged. Significantly...

  15. Condition of pro-oxidant and antioxidant systems in guinea pigs’ lungs under the condition of immobilization stress

    Directory of Open Access Journals (Sweden)

    Mykhailo Stepanovych Reheda

    2017-11-01

    Full Text Available We have investigated the results of alterations in indices of pro-oxidant (conjugated diene and malondialdehyde and antioxidant (superoxide dismutase, ceruloplasmin, catalase systems in guinea pigs’ lungs  under the conditions of immobilization stress. The experiment was conducted on 40 female guinea pigs weighing 0.18-0.20 kg. The animals were divided into 4 groups, each contained 10 guinea pigs: I – intact guinea pigs ( control, II–guinea pigs with model of IS on1st day of experiment;Ш–animals on 2nd  day of experiment;IV- group of animals on 34th day of experimental model of IS. The results of our experimental work showed  a significant accumulation of lipid peroxidation products in the lung`s tissure in different periods ( on 1st, 2nd and 34th days of immobilization stress. The state of antioxidant defence was characterized by moderate decrease of inzymes activity (superoxide dismutase, catalase and ceruloplasmin. disorders of balance between pro-oxidant and antioxidant systems couse oxidative stress development.

  16. Antioxidant activity and sensory analysis of murtilla (Ugni molinae Turcz. fruit extracts in an oil model system

    Directory of Open Access Journals (Sweden)

    T. R. Augusto-Obara

    2017-03-01

    Full Text Available An oil model system was used to analyze the antioxidant activity of Chilean fruit extracts and to determine their odor sensory effect. Hydroalcoholic extracts from wild and 14-4 genotype murtilla (Ugni molinae Turcz. fruit were assessed by the Response Surface Methodology. The optimal conditions for producing high total phenolic-content extracts were 49.5% (v/v ethanol at 30 ºC, which yielded 18.39 and 26.14 mg GAE·g-1 dry matter, respectively. The optimized extracts were added to a lipid model system and evaluated via the Schaal Oven Test. After 96 hours, 150 and 200 mg·kg-1 oil of the wild and 14-4 genotype extracts, respectively, showed an antioxidant capacity similar to TBHQ (200 mg·kg-1 oil in terms of peroxide values and odor. Thus, murtilla fruit extracts are a natural source of antioxidants for protecting lipidic foods, such as soybean oil.

  17. Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects.

    Science.gov (United States)

    Frank, Thomas; Netzel, Gabriele; Kammerer, Dietmar R; Carle, Reinhold; Kler, Adolf; Kriesl, Erwin; Bitsch, Irmgard; Bitsch, Roland; Netzel, Michael

    2012-08-15

    To evaluate health benefits attributed to Hibiscus sabdariffa L. a randomized, open-label, two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract (HSE) on the systemic antioxidant potential (AOP; assayed by ferric reducing antioxidant power (FRAP)) with a reference treatment (water) in eight healthy volunteers. The biokinetic variables were the areas under the curve (AUC) of plasma FRAP, ascorbic acid and urate that are above the pre-dose concentration, and the amounts excreted into urine within 24 h (Ae(0-24) ) of antioxidants as assayed by FRAP, ascorbic acid, uric acid, malondialdehyde (biomarker for oxidative stress), and hippuric acid (metabolite and potential biomarker for total polyphenol intake). HSE caused significantly higher plasma AUC of FRAP, an increase in Ae(0-24) of FRAP, ascorbic acid and hippuric acid, whereas malondialdehyde excretion was reduced. Furthermore, the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers' urine (0.02% of the administered dose). The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans. Furthermore, the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols, most likely caused by the colonic microbiota. Copyright © 2012 Society of Chemical Industry.

  18. In vitro antioxidant and cytoprotective properties of Maillard reaction products from phloridzin-amino acid model systems.

    Science.gov (United States)

    Han, Linna; Li, Feng; Yu, Qijian; Li, Dapeng

    2018-01-01

    The aim of this study was to investigate in vitro antioxidant activities and cytoprotective effect of Maillard reaction products (MRPs) from phloridzin (Pz)-amino acid model systems. Their structures were also characterised by Fourier transform-infrared spectroscopy (FTIR). MRPs were prepared from the Pz-methionine (Met), Pz-lysine (Lys), Pz-isoleucine (Ile), Pz-histidine (His) or Pz-glutamic acid (Glu) model system. The Pz-Lys MRPs, rich in antioxidant potency, were subjected to ultrafiltration to yield four MRPs fractions with different molecular weights (Mw). The fraction with Mw 30-50 kDa had significantly (P Maillard reaction. The results obtained in this study may provide some basis for the purported health-promoting effects of MRPs and their potential application as antioxidant agents in food industry. Also, it is important for our understanding of the variation of bioactive substances in food during thermal processing. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  19. The Responses of Antioxidant System against the Heavy Metal-Induced Stress in Tomato

    Directory of Open Access Journals (Sweden)

    Dursun KISA

    2017-12-01

    Full Text Available Plants maintain their life cycles under the various environmental conditions such as oxidative stress induced by heavy metals. Accumulation of metal ions in plants causes the formation of free radicals and stimulates the antioxidative defense systems. In this study, the activities of APX, POD, and SOD are investigated in the leaves and roots of tomato cultivated under the heavy metal-induced stress. The activities of APX, POD, and SOD exhibited remarkable induction with the treatment of Cd, Cu and Pb (10, 20 and 50 ppm in the leaves of tomato compared to control plants except for 50 ppm Pb. In roots, APX activity changed depending on the heavy metal types and concentrations, while Cd clearly increased it with stress conditions, but Cu decreased in tomato compared to control. The activity of POD clearly exhibited that the all doses of heavy metals reduced the enzyme activity in roots polluted with heavy metals. The treatment of Cd (10, 20 and 50 ppm significantly increased the activity of SOD, however, Cu showed the opposite effect which significantly decreased with increasing doses in roots compared to uncontaminated plants. Also, roots from plants grown on the high concentration of Pb (20 and 50 ppm induced the activity of SOD. Briefly, it is clear responses which Cd significantly raised the activities of APX and SOD in leaves and roots of tomato. The decreases caused by these metals in the activity of POD and Cu in the activities of APX and SOD in roots of tomato can be clarified by the result of heavy metal-induced the over production of free radical.

  20. Vanadyl sulfate, taurine, and combined vanadyl sulfate and taurine treatments in diabetic rats: effects on the oxidative and antioxidative systems.

    Science.gov (United States)

    Tas, Sibel; Sarandol, Emre; Ayvalik, Sedef Ziyanok; Serdar, Zehra; Dirican, Melahat

    2007-04-01

    Vanadyl sulfate (VS) and taurine are two promising agents in the treatment of diabetes related to their antihyperglycemic, antihyperlipidemic, and hyperinsulinemic effects. Data about the effects of VS on the oxidant-antioxidant system is limited and controversial. However, taurine is a well-documented antioxidant agent and our aim was to investigate the effects of VS, taurine and VS and taurine combination on the oxidative-antioxidative systems in streptozotocin-nicotinamide (STZ-NA) diabetic rats. Nicotinamide (230 mg/kg, i.p.) and streptozotocin (65 mg/kg, i.p.) were administered. VS (0.75 mg/mL) and taurine (1%) were added to drinking water for 5 weeks. Rats were divided as control (C), diabetes (D), diabetes+VS (D+VS), diabetes+taurine (D+T), diabetes+VS and taurine (D+VST). Plasma and tissue malondialdehyde (MDA) levels were measured by high-performance liquid chromatography and spectrophotometry, respectively. Paraoxonase and arylesterase activities were measured by spectrophotometric methods and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined using commercial kits. VS, taurine and VS and taurine combination treatments reduced the enhanced blood glucose, serum total cholesterol and triglyceride, tissue MDA and plasma MDA (except in the D+VS group) levels and increased the reduced serum insulin level, serum paraoxonase and arylesterase activities, GSH-Px activity and SOD activity (except in the D+VS group). The findings of the present study suggest that VS and taurine exert beneficial effects on the blood glucose and lipid levels in STZ-NA diabetic rats. However, VS might exert prooxidative or antioxidative effects in various components of the body and taurine and VS combination might be an alternative for sole VS administration.

  1. Optimised formation of blue Maillard reaction products of xylose and glycine model systems and associated antioxidant activity.

    Science.gov (United States)

    Yin, Zi; Sun, Qian; Zhang, Xi; Jing, Hao

    2014-05-01

    A blue colour can be formed in the xylose (Xyl) and glycine (Gly) Maillard reaction (MR) model system. However, there are fewer studies on the reaction conditions for the blue Maillard reaction products (MRPs). The objective of this study is to investigate characteristic colour formation and antioxidant activities in four different MR model systems and to determine the optimum reaction conditions for the blue colour formation in a Xyl-Gly MR model system, using the random centroid optimisation program. The blue colour with an absorbance peak at 630 nm appeared before browning in the Xyl-Gly MR model system, while no blue colour formation but only browning was observed in the xylose-alanine, xylose-aspartic acid and glucose-glycine MR model systems. The Xyl-Gly MR model system also showed higher antioxidant activity than the other three model systems. The optimum conditions for blue colour formation were as follows: xylose and glycine ratio 1:0.16 (M:M), 0.20 mol L⁻¹ NaHCO₃, 406.1 mL L⁻¹ ethanol, initial pH 8.63, 33.7°C for 22.06 h, which gave a much brighter blue colour and a higher peak at 630 nm. A characteristic blue colour could be formed in the Xyl-Gly MR model system and the optimum conditions for the blue colour formation were proposed and confirmed. © 2013 Society of Chemical Industry.

  2. Pycnogenol Attenuates the Release of Proinflammatory Cytokines and Expression of Perilipin 2 in Lipopolysaccharide-Stimulated Microglia in Part via Inhibition of NF-κB and AP-1 Activation.

    Directory of Open Access Journals (Sweden)

    Bin Fan

    Full Text Available Over activation of microglia results in the production of proinflammatory agents that have been implicated in various brain diseases. Pycnogenol is a patented extract from French maritime pine bark (Pinus pinaster Aiton with strong antioxidant and anti-inflammatory potency. The present study investigated whether pycnogenol may be associated with the production of proinflammatory mediators in lipopolysaccharide-stimulated BV2 (mouse-derived microglia. It was found that pycnogenol treatment was dose-dependently associated with significantly less release of nitricoxide (NO, TNF-α, IL-6 and IL-1β, and lower levels of intercellular adhesion molecule1 (ICAM-1 and perilipin 2 (PLIN2. Furthermore, this effect was replicated in primary brain microglia. Levels of inducible NO synthase mRNA and protein were attenuated, whereas there was no change in the production of the anti-inflammatory cytokine IL-10. Further evidence indicated that pycnogenol treatment led to the suppression of NF-κB activation through inhibition of p65 translocation into the nucleus and inhibited DNA binding of AP-1, suggesting that these proinflammatory factors are associated with NF-κB and AP-1. We conclude that pycnogenol exerts anti-inflammatory effects through inhibition of the NF-κB and AP-1pathway, and may be useful as a therapeutic agent in the prevention of diseases caused by over activation of microglia.

  3. Effects of artea, a systemic fungicide, on the antioxidant system and ...

    African Journals Online (AJOL)

    The present work aimed at the study of the effects of Artea, a systemic azole fungicide, on durum Wheat (Triticum durum L. cv. GTA dur). Seeds were grown in a medium containing respectively 25, 50, 75 and 100 ppm of Artea under controlled conditions. Roots of eight-day-old plants were used to determine catalase, ...

  4. Influence of separate and combined impact both of radiation and chemical factors on state of lipid peroxide oxidation system and antioxidant protection at pregnant rats

    International Nuclear Information System (INIS)

    Danil'chik, V.S.; Spivak, L.V.; Kolb, V.G.; Zubovskaya, E.T.; Rogov, Yu.I.

    2000-01-01

    Influence of low dozed ionizing irradiation and chemical toxicant was studied both under separate and combined action in the process of pregnancy. The lipid peroxidation (LPO) indices and antioxidant protection (AOP) parameters of females rats were studied. The result received proved that irradiation during pregnancy induced activation both of lipids free radical oxidation and of antioxidant protection in female rats. Chemical toxicants introduction resulted in shifts on the LPO-AOP system the hydrogen peroxide blood level increasing and the antioxidants ones reducing. Combined action of both factors led to development of a new level of LPO-AOP

  5. Influence of Roasting on the Antioxidant Activity and HMF Formation of a Cocoa Bean Model Systems

    NARCIS (Netherlands)

    Oliviero, T.; Capuano, E.; Cämmerer, B.; Fogliano, V.

    2009-01-01

    During the roasting of cocoa beans chemical reactions lead to the formation of Maillard reaction (MR) products and to the degradation of catechin-containing compounds, which are very abundant in these seeds. To study the modifications occurring during thermal treatment of fat and antioxidant rich

  6. A comparison of chemical systems for luminometric determination of antioxidant capacity towards individual reactive oxygen species

    Czech Academy of Sciences Publication Activity Database

    Komrsková, Daniela; Lojek, Antonín; Hrbáč, J.; Číž, Milan

    2006-01-01

    Roč. 21, č. 4 (2006), s. 239-244 ISSN 1522-7235 R&D Projects: GA ČR(CZ) GA524/01/1219 Institutional research plan: CEZ:AV0Z50040507 Keywords : antioxidant capacity * luminometry Subject RIV: BO - Biophysics Impact factor: 0.874, year: 2006

  7. The Assessment of the Integrated Antioxidant System of the Body in the Course of Radon Therapy: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Jadwiga Kuciel-Lewandowska

    2018-01-01

    Full Text Available Introduction. The sources of Reactive Oxidative Species (ROS in the organism are the respiratory processes occurring in cells catalyzed by different enzymes. Operation of ROS is balanced by antioxidants, the compounds; although present in low concentrations, they significantly inhibit the degree of oxidation of particular molecules. The Aim of the Study. The aim of this study was to assess the changes in the integrated antioxidant system under the influence of radon therapy in osteoarthritis patients. Material and Methods. Observation included 35 patients suffering from degenerative joints and disc disease (mean age 56.5 years undergoing radon water therapy and control group that consisted of 15 osteoarthritis patients (mean age 54.2 without contact with radon water. Before therapy and after 18 days of treatment, serum total antioxidant status (TAS was assessed with the use of standard colorimetric assay. Results. In the study group, we observed trends to increase TAS concentration, whereas, in the control group, TAS concentration was decreasing. Conclusions. (1 Radon waters treatment influenced the level of TAS of osteoarthritis patients treated with the radon water. (2 The change in TAS concentrations in the study group may be the result of low doses of ionizing radiation, but further studies on larger patient’s groups are demanded. This study is registered with number NCT03274128.

  8. Effects of Dietary Lycopene Supplementation on Plasma Lipid Profile, Lipid Peroxidation and Antioxidant Defense System in Feedlot Bamei Lamb.

    Science.gov (United States)

    Jiang, Hongqin; Wang, Zhenzhen; Ma, Yong; Qu, Yanghua; Lu, Xiaonan; Luo, Hailing

    2015-07-01

    Lycopene, a red non-provitamin A carotenoid, mainly presenting in tomato and tomato byproducts, has the highest antioxidant activity among carotenoids because of its high number of conjugated double bonds. The objective of this study was to investigate the effect of lycopene supplementation in the diet on plasma lipid profile, lipid peroxidation and antioxidant defense system in feedlot lamb. Twenty-eight Bamei male lambs (90 days old) were divided into four groups and fed a basal diet (LP0, 40:60 roughage: concentrate) or the basal diet supplemented with 50, 100, and 200 mg/kg lycopene. After 120 days of feeding, all lambs were slaughtered and sampled. Dietary lycopene supplementation significantly reduced the levels of plasma total cholesterol (p0.05). The levels of TG (pCAT, pCAT (p<0.05, linearly) and SOD (p<0.001, linearly). Therefore, it was concluded that lycopene supplementation improved the antioxidant status of the lamb and optimized the plasma lipid profile, the dosage of 200 mg lycopene/kg feed might be desirable for growing lambs to prevent environment stress and maintain normal physiological metabolism.

  9. Effects of Polysaccharide-Based Edible Coatings on Quality and Antioxidant Enzyme System of Strawberry during Cold Storage

    Directory of Open Access Journals (Sweden)

    Li Li

    2017-01-01

    Full Text Available Strawberry is a nutritious, but highly perishable fruit. Three polysaccharide-based edible coatings (alginate, chitosan, and pullulan were applied to postharvest strawberry fruit during cold storage (4°C, and their effects on fruit quality and antioxidant enzyme system were investigated in the present study. The results showed that polysaccharide coatings showed a significant delay in fruit softening and rot and reduced changes in total soluble solid and titratable acidity content during 16 d storage. Polysaccharide coatings also maintained higher ascorbic acid and total phenolic contents than control from day 2 and significantly inhibited fruit decay and respiration after 12 d storage (p<0.05. Polysaccharide treatments enhanced the activities of antioxidant enzymes (peroxidase, catalase, superoxide dismutase, and ascorbate peroxidase so as to prevent lipid peroxidation and reduce membrane damage. Additionally, chitosan coating had the most positive effects on fruit quality amongst three polysaccharide-based edible coatings and presented the highest relative activities of antioxidant enzymes. These results indicated that polysaccharide-based edible coatings were helpful in postharvest quality maintenance of strawberry fruit.

  10. Comparison of effects on the oxidant/antioxidant system of sevoflurane, desflurane and propofol infusion during general anesthesia

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    Mesut Erbas

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: Desflurane and sevoflurane are frequently used for maintenance of anesthesia and studies have shown that these anesthetics cause a variety of changes to the oxidative stress and antioxidative defense mechanisms. This study aims to compare the effects of sevoflurane, desflurane and propofol infusion anesthesia on the oxidant and antioxidant systems of patients undergoing laparoscopic cholecystectomy. METHODS: 45 patients between 18 and 50 years with planned laparoscopic cholecystectomy under general anesthetic were included in the study. Patients were divided into three groups on the way to surgery: propofol (group P n: 15, sevoflurane (group S n: 15 and desflurane (group D n: 15. All groups were given hypnotic 2 mg/kg propofol IV, 1 mcg/kg fentanyl IV and 0.1 mg/kg vecuronium IV for induction. For maintenance of anesthesia group S were ventilated with 2% sevoflurane, group D cases were given 6% desflurane and group P were given propofol infusions of 12 mg/kg/h for the first 10 min, 9 mg/kg/h for the second 10 min and 6 mg/kg/h after that. Before induction and after the operation venous blood samples were taken to evaluate the levels of glutation peroxidase, total oxidants and antioxidants. RESULTS AND CONCLUSIONS: The 45 patients included in the study were 22 male and 23 female patients. The demographic characteristics of the groups were similar. In the postoperative period we observed that while sevoflurane and propofol increased antioxidants by a statistically significant level, desflurane increased the total oxidants level by a significant amount compared to levels before the operation.

  11. Beta-carotene reduces oxidative stress, improves glutathione metabolism and modifies antioxidant defense systems in lead-exposed workers

    International Nuclear Information System (INIS)

    Kasperczyk, Sławomir; Dobrakowski, Michał; Kasperczyk, Janusz; Ostałowska, Alina; Zalejska-Fiolka, Jolanta; Birkner, Ewa

    2014-01-01

    The aim of this study was to determine whether beta-carotene administration reduces oxidative stress and influences antioxidant, mainly glutathione-related, defense systems in workers chronically exposed to lead. The population consisted of two randomly divided groups of healthy male volunteers exposed to lead. Workers in the first group (reference group) were not administered any antioxidants, while workers in the second group (CAR group) were treated orally with 10 mg of beta-carotene once a day for 12 weeks. Biochemical analysis included measuring markers of lead-exposure and oxidative stress in addition to the levels and activities of selected antioxidants. After treatment, levels of malondialdehyde, lipid hydroperoxides and lipofuscin significantly decreased compared with the reference group. However, the level of glutathione significantly increased compared with the baseline. Treatment with beta-carotene also resulted in significantly decreased glutathione peroxidase activity compared with the reference group, while the activities of other glutathione-related enzymes and of superoxide dismutase were not significantly changed. However, the activities of glucose-6-phosphate dehydrogenase and catalase, as well as the level of alpha-tocopherol, were significantly higher after treatment compared with the baseline. Despite controversy over the antioxidant properties of beta-carotene in vivo, our findings showed reduced oxidative stress after beta-carotene supplementation in chronic lead poisoning. - Highlights: • Beta-carotene reduces oxidative stress in lead-exposed workers. • Beta-carotene elevates glutathione level in lead-exposed workers. • Beta-carotene administration could be beneficial in lead poisoning

  12. Beta-carotene reduces oxidative stress, improves glutathione metabolism and modifies antioxidant defense systems in lead-exposed workers

    Energy Technology Data Exchange (ETDEWEB)

    Kasperczyk, Sławomir, E-mail: kaslav@mp.pl [Dept. of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland); Dobrakowski, Michał [Dept. of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland); Kasperczyk, Janusz [Dept. of Environmental Medicine and Epidemiology, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland); Ostałowska, Alina; Zalejska-Fiolka, Jolanta; Birkner, Ewa [Dept. of Biochemistry, School of Medicine with the Division of Dentistry, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze (Poland)

    2014-10-01

    The aim of this study was to determine whether beta-carotene administration reduces oxidative stress and influences antioxidant, mainly glutathione-related, defense systems in workers chronically exposed to lead. The population consisted of two randomly divided groups of healthy male volunteers exposed to lead. Workers in the first group (reference group) were not administered any antioxidants, while workers in the second group (CAR group) were treated orally with 10 mg of beta-carotene once a day for 12 weeks. Biochemical analysis included measuring markers of lead-exposure and oxidative stress in addition to the levels and activities of selected antioxidants. After treatment, levels of malondialdehyde, lipid hydroperoxides and lipofuscin significantly decreased compared with the reference group. However, the level of glutathione significantly increased compared with the baseline. Treatment with beta-carotene also resulted in significantly decreased glutathione peroxidase activity compared with the reference group, while the activities of other glutathione-related enzymes and of superoxide dismutase were not significantly changed. However, the activities of glucose-6-phosphate dehydrogenase and catalase, as well as the level of alpha-tocopherol, were significantly higher after treatment compared with the baseline. Despite controversy over the antioxidant properties of beta-carotene in vivo, our findings showed reduced oxidative stress after beta-carotene supplementation in chronic lead poisoning. - Highlights: • Beta-carotene reduces oxidative stress in lead-exposed workers. • Beta-carotene elevates glutathione level in lead-exposed workers. • Beta-carotene administration could be beneficial in lead poisoning.

  13. Antioxidant Activity of Ixora parviflora in a Cell/Cell-Free System and in UV-Exposed Human Fibroblasts

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    Hsiu-Mei Chiang

    2011-07-01

    Full Text Available Polyphenols and flavonoids possess a variety of biological activities including antioxidant and anti-tumor activities. Ixora parviflora is a member of the flavonoid-rich Rubiaceae family of flowering plants and used as folk medicine in India. The aim of this study was to investigate the antioxidant activity of Ixora parviflora extract (IPE in a cell-free system and erythrocytes, and the ability of IPE to inhibit reactive oxygen species (ROS generation in human fibroblasts (Hs68 after ultraviolet (UV exposure. Various in vitro antioxidant assays were employed in this study. The extraction yield of IPE was 17.4 ± 3.9%, the total phenolic content of IPE was 26.2 μg gallic acid equivalent (GAE/mg leaves dry weight and the total flavonoids content was 54.2 ± 4.4 μg quercetin equvalent (QE/mg extract. The content of chlorogenic acid was 9.7 ± 1.2 mg/g extract. IPE at 1000 μg/mL exhibited a reducing capacity of 90.5 ± 0.6%, a 1,1-diphenyl-2-picrylhydrazy (DPPH radical scavenging activity of 96.0 ± 0.4%, a ferrous chelating activity of 72.2 ± 3.5%, a hydroxyl radical scavenging activity of 96.8 ± 1.4%, and a hydrogen peroxide scavenging activity of 99.5 ± 3.3%. IPE at 500 μg/mL also possessed inhibitory activity against 2,2'-azobis (2-methylpropionamidine dihydrochloride (AAPH-induced hemolysis of erythrocytes (89.4 ± 1.8% and resulted in a 52.9% reduction in ROS generation in UV-exposed fibroblasts. According to our findings, IPE is a potent antioxidant and a potential anti-photoaging agent.

  14. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity

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    R. Andrew Shanely

    2016-08-01

    Full Text Available Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125. Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05, however, the rating of perceived exertion was greater during the WM trial (p > 0.05. WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05, but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine, antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function.

  15. Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats

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    Biernacki, Michał; Łuczaj, Wojciech; Gęgotek, Agnieszka [Department of Analytical Chemistry Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok (Poland); Toczek, Marek [Department of Experimental Physiology and Pathophysiology Medical University of Bialystok, Mickiewicza 2A, 15-222 Bialystok (Poland); Bielawska, Katarzyna [Department of Analytical Chemistry Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok (Poland); Skrzydlewska, Elżbieta, E-mail: elzbieta.skrzydlewska@umb.edu.pl [Department of Analytical Chemistry Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok (Poland)

    2016-06-15

    Hypertension is accompanied by perturbations to the endocannabinoid and antioxidant systems. Thus, potential pharmacological treatments for hypertension should be examined as modulators of these two metabolic systems. The aim of this study was to evaluate the effects of chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate (URB597) on the endocannabinoid system and on the redox balance in the livers of DOCA-salt hypertensive rats. Hypertension caused an increase in the levels of endocannabinoids [anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-dopamine (NADA)] and CB{sub 1} receptor and the activities of FAAH and monoacylglycerol lipase (MAGL). These effects were accompanied by an increase in the level of reactive oxygen species (ROS), a decrease in antioxidant activity/level, enhanced expression of transcription factor Nrf2 and changes to Nrf2 activators and inhibitors. Moreover, significant increases in lipid, DNA and protein oxidative modifications, which led to enhanced levels of proapoptotic caspases, were also observed. URB597 administration to the hypertensive rats resulted in additional increases in the levels of AEA, NADA and the CB{sub 1} receptor, as well as decreases in vitamin E and C levels, glutathione peroxidase and glutathione reductase activities and Nrf2 expression. Thus, after URB597 administration, oxidative modifications of cellular components were increased, while the inflammatory response was reduced. This study revealed that chronic treatment of hypertensive rats with URB597 disrupts the endocannabinoid system, which causes an imbalance in redox status. This imbalance increases the levels of electrophilic lipid peroxidation products, which later participate in metabolic disturbances in liver homeostasis. - Highlights: • Chronic administration of URB597 to hypertensive rats reduces liver inflammation. • URB597 enhances the redox imbalance in the

  16. Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats

    International Nuclear Information System (INIS)

    Biernacki, Michał; Łuczaj, Wojciech; Gęgotek, Agnieszka; Toczek, Marek; Bielawska, Katarzyna; Skrzydlewska, Elżbieta

    2016-01-01

    Hypertension is accompanied by perturbations to the endocannabinoid and antioxidant systems. Thus, potential pharmacological treatments for hypertension should be examined as modulators of these two metabolic systems. The aim of this study was to evaluate the effects of chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate (URB597) on the endocannabinoid system and on the redox balance in the livers of DOCA-salt hypertensive rats. Hypertension caused an increase in the levels of endocannabinoids [anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-dopamine (NADA)] and CB 1 receptor and the activities of FAAH and monoacylglycerol lipase (MAGL). These effects were accompanied by an increase in the level of reactive oxygen species (ROS), a decrease in antioxidant activity/level, enhanced expression of transcription factor Nrf2 and changes to Nrf2 activators and inhibitors. Moreover, significant increases in lipid, DNA and protein oxidative modifications, which led to enhanced levels of proapoptotic caspases, were also observed. URB597 administration to the hypertensive rats resulted in additional increases in the levels of AEA, NADA and the CB 1 receptor, as well as decreases in vitamin E and C levels, glutathione peroxidase and glutathione reductase activities and Nrf2 expression. Thus, after URB597 administration, oxidative modifications of cellular components were increased, while the inflammatory response was reduced. This study revealed that chronic treatment of hypertensive rats with URB597 disrupts the endocannabinoid system, which causes an imbalance in redox status. This imbalance increases the levels of electrophilic lipid peroxidation products, which later participate in metabolic disturbances in liver homeostasis. - Highlights: • Chronic administration of URB597 to hypertensive rats reduces liver inflammation. • URB597 enhances the redox imbalance in the liver of

  17. Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis.

    Science.gov (United States)

    Azevedo, E P; Ledo, J H; Barbosa, G; Sobrinho, M; Diniz, L; Fonseca, A C C; Gomes, F; Romão, L; Lima, F R S; Palhano, F L; Ferreira, S T; Foguel, D

    2013-09-05

    Oculoleptomeningeal amyloidosis (OA) is a fatal and untreatable hereditary disease characterized by the accumulation of transthyretin (TTR) amyloid within the central nervous system. The mechanisms underlying the pathogenesis of OA, and in particular how amyloid triggers neuronal damage, are still unknown. Here, we show that amyloid fibrils formed by a mutant form of TTR, A25T, activate microglia, leading to the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide. Further, we found that A25T amyloid fibrils induce the activation of Akt, culminating in the translocation of NFκB to the nucleus of microglia. While A25T fibrils were not directly toxic to neurons, the exposure of neuronal cultures to media conditioned by fibril-activated microglia caused synapse loss that culminated in extensive neuronal death via apoptosis. Finally, intracerebroventricular (i.c.v.) injection of A25T fibrils caused microgliosis, increased brain TNF-α and IL-6 levels and cognitive deficits in mice, which could be prevented by minocycline treatment. These results indicate that A25T fibrils act as pro-inflammatory agents in OA, activating microglia and causing neuronal damage.

  18. Neuron-derived IgG protects dopaminergic neurons from insult by 6-OHDA and activates microglia through the FcγR I and TLR4 pathways.

    Science.gov (United States)

    Zhang, Jie; Niu, Na; Wang, Mingyu; McNutt, Michael A; Zhang, Donghong; Zhang, Baogang; Lu, Shijun; Liu, Yuqing; Liu, Zhihui

    2013-08-01

    Oxidative and immune attacks from the environment or microglia have been implicated in the loss of dopaminergic neurons of Parkinson's disease. The role of IgG which is an important immunologic molecule in the process of Parkinson's disease has been unclear. Evidence suggests that IgG can be produced by neurons in addition to its traditionally recognized source B lymphocytes, but its function in neurons is poorly understood. In this study, extensive expression of neuron-derived IgG was demonstrated in dopaminergic neurons of human and rat mesencephalon. With an in vitro Parkinson's disease model, we found that neuron-derived IgG can improve the survival and reduce apoptosis of dopaminergic neurons induced by 6-hydroxydopamine toxicity, and also depress the release of NO from microglia triggered by 6-hydroxydopamine. Expression of TNF-α and IL-10 in microglia was elevated to protective levels by neuron-derived IgG at a physiologic level via the FcγR I and TLR4 pathways and microglial activation could be attenuated by IgG blocking. All these data suggested that neuron-derived IgG may exert a self-protective function by activating microglia properly, and IgG may be involved in maintaining immunity homeostasis in the central nervous system and serve as an active factor under pathological conditions such as Parkinson's disease. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  19. Regulation of microglia activity by glaucocalyxin-A: attenuation of lipopolysaccharide-stimulated neuroinflammation through NF-κB and p38 MAPK signaling pathways.

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    Byung-Wook Kim

    Full Text Available Microglial cells are the resident macrophages and intrinsic arm of the central nervous system innate immune defense. Microglial cells become activated in response to injury, infection, environmental toxins, and other stimuli that threaten neuronal survival. Therefore, regulating microglial activation may have therapeutic benefits that lead to alleviating the progression of inflammatory-mediated neurodegeneration. In the present study, we investigated the effect of glaucocalyxin A (GLA isolated from Rabdosia japonica on the production of pro-inflammatory mediators in lipopolysaccharide (LPS-stimulated primary microglia and BV-2 cells. GLA significantly inhibited LPS-induced production of nitric oxide and reversed the morphological changes in primary microglia. Further, GLA suppressed expression of inducible nitric oxide synthase and cyclooxygenase-2 dose-dependently at the mRNA and protein levels. The production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1β (IL-1β, and IL-6 were inhibited by suppressing their transcriptional activity. Furthermore, GLA suppressed nuclear factor-κB activation by blocking degradation of IκB-α and inhibited the induction of lipocalin-2 expression in LPS-stimulated BV-2 cells. Mechanistic study revealed that the inhibitory effects of GLA were accompanied by blocking the p38 mitogen activated protein kinase signaling pathway in activated microglia. In conclusion, given that microglial activation contributes to the pathogenesis of neurodegenerative diseases, GLA could be developed as a potential therapeutic agent for treating microglia-mediated neuroinflammatory diseases.

  20. The Plant-Derived Chalcone 2,2′,5′-Trihydroxychalcone Provides Neuroprotection against Toll-Like Receptor 4 Triggered Inflammation in Microglia

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    Manasi Jiwrajka

    2016-01-01

    Full Text Available Chalcones are plant metabolites with potential for therapeutic exploitation as antioxidant, anti-inflammatory, and antiproliferative agents. Here we explored the neuroprotective effects of 2,2′,5′-trihydroxychalcone (225THC, a potent antioxidant with radical-scavenging properties. 225THC was found to be a potent inhibitor of apoptosis in stimulated primary rat neuronal cultures. This was likely mediated by an anti-inflammatory effect on microglial cells since 225THC inhibited LPS-stimulated TNF-α and IL-6 secretion from primary rat microglia and modulated the cytokine/chemokine profile of BV2 microglial cells. Additionally, 225THC inhibited LPS-evoked inducible nitric oxide synthase expression but did not influence endogenous superoxide generation. Microglial flow cytometric analyses indicated the 225THC treatment induced a shift from an M1-like phenotype to a more downregulated microglial profile. Taken together these data suggest that the chalcone 2,2′,5′-trihydroxychalcone can modulate neuroinflammatory activation in brain-derived microglia and holds promise as a therapeutic in neuroinflammatory conditions.

  1. Microglia Activation, Herpes Infection, and NMDA Receptor Inhibition : Common Pathways to Psychosis?

    NARCIS (Netherlands)

    Klein, Hans C.; Doorduin, Janine; de Witte, Lot; de Vries, Erik; Müller, Norbert; Myint, Aye-Mu; Schwarz, Markus J.

    2015-01-01

    Microglia are the resident macrophages of the brain. Microglia play important housekeeping roles during brain development and during exposure to psychosocial stress, toxins, and infectious pathogens. The hippocampus is a vulnerable brain region in response to these external stressors. In patients

  2. Microglia kill amyloid-beta1-42 damaged neurons by a CD14-dependent process

    NARCIS (Netherlands)

    Bate, Clive; Veerhuis, Robert; Eikelenboom, Piet; Williams, Alun

    2004-01-01

    Activated microglia are closely associated with neuronal damage in Alzheimer's disease. In the present study, neurons exposed to low concentrations of amyloid-beta1-42, a toxic fragment of the amyloid-beta protein, were killed by microglia in a process that required cell-cell contact. Pre-treating

  3. Cellular and Molecular Characterization of Microglia : A Unique Immune Cell Population

    NARCIS (Netherlands)

    Sousa, Carole; Biber, Knut; Michelucci, Alessandro

    2017-01-01

    Microglia are essential for the development and function of the adult brain. Microglia arise from erythro-myeloid precursors in the yolk sac and populate the brain rudiment early during development. Unlike monocytes that are constantly renewed from bone marrow hematopoietic stem cells throughout

  4. Toll-like receptor activation reveals developmental reorganization and unmasks responder subsets of microglia

    NARCIS (Netherlands)

    Scheffel, Joerg; Regen, Tommy; Van Rossum, Denise; Seifert, Stefanie; Ribes, Sandra; Nau, Roland; Parsa, Roham; Harris, Robert A.; Boddeke, Hendrikus W. G. M.; Chuang, Han-Ning; Pukrop, Tobias; Wessels, Johannes T.; Juergens, Tanja; Merkler, Doron; Brueck, Wolfgang; Schnaars, Mareike; Simons, Mikael; Kettenmann, Helmut; Hanisch, Uwe-Karsten

    2012-01-01

    The sentinel and immune functions of microglia require rapid and appropriate reactions to infection and damage. Their Toll-like receptors (TLRs) sense both as threats. However, whether activated microglia mount uniform responses or whether subsets conduct selective tasks is unknown. We demonstrate

  5. Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation.

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    Asya Rolls

    2008-08-01

    Full Text Available BACKGROUND: Chondroitin sulfate proteoglycan (CSPG is a major component of the glial scar. It is considered to be a major obstacle for central nervous system (CNS recovery after injury, especially in light of its well-known activity in limiting axonal growth. Therefore, its degradation has become a key therapeutic goal in the field of CNS regeneration. Yet, the abundant de novo synthesis of CSPG in response to CNS injury is puzzling. This apparent dichotomy led us to hypothesize that CSPG plays a beneficial role in the repair process, which might have been previously overlooked because of nonoptimal regulation of its levels. This hypothesis is tested in the present study. METHODS AND FINDINGS: We inflicted spinal cord injury in adult mice and examined the effects of CSPG on the recovery process. We used xyloside to inhibit CSPG formation at different time points after the injury and analyzed the phenotype acquired by the microglia/macrophages in the lesion site. To distinguish between the resident microglia and infiltrating monocytes, we used chimeric mice whose bone marrow-derived myeloid cells expressed GFP. We found that CSPG plays a key role during the acute recovery stage after spinal cord injury in mice. Inhibition of CSPG synthesis immediately after injury impaired functional motor recovery and increased tissue loss. Using the chimeric mice we found that the immediate inhibition of CSPG production caused a dramatic effect on the spatial organization of the infiltrating myeloid cells around the lesion site, decreased insulin-like growth factor 1 (IGF-1 production by microglia/macrophages, and increased tumor necrosis factor alpha (TNF-alpha levels. In contrast, delayed inhibition, allowing CSPG synthesis during the first 2 d following injury, with subsequent inhibition, improved recovery. Using in vitro studies, we showed that CSPG directly activated microglia/macrophages via the CD44 receptor and modulated neurotrophic factor secretion by

  6. Ozone Therapy on Rats Submitted to Subtotal Nephrectomy: Role of Antioxidant System

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    José Luis Calunga

    2005-01-01

    Full Text Available Chronic renal failure (CRF represents a world health problem. Ozone increases the endogenous antioxidant defense system, preserving the cell redox state. The aim of this study is to evaluate the effect of ozone/oxygen mixture in the renal function, morphology, and biochemical parameters, in an experimental model of CRF (subtotal nephrectomy. Ozone/oxygen mixture was applied daily, by rectal insufflation (0.5 mg/kg for 15 sessions after the nephrectomy. Renal function was evaluated, as well as different biochemical parameters, at the beginning and at the end of the study (10 weeks. Renal plasmatic flow (RPF, glomerular filtration rate (GFR, the urine excretion index, and the sodium and potassium excretions (as a measurement of tubular function in the ozone group were similar to those in Sham group. Nevertheless, nephrectomized rats without ozone (positive control group showed the lowest RPF, GFR, and urine excretion figures, as well as tubular function. Animals treated with ozone showed systolic arterial pressure (SAP figures lower than those in the positive control group, but higher values compared to Sham group. Serum creatinine values and protein excretion in 24 hours in the ozone group were decreased compared with nephrectomized rats, but were still higher than normal values. Histological study demonstrated that animals treated with ozone showed less number of lesions in comparison with nephrectomized rats. Thiobarbituric acid reactive substances were significantly increased in nephrectomized and ozone-treated nephrectomized rats in comparison with Sham group. In the positive control group, superoxide dismutase (SOD and catalase (CAT showed the lowest figures in comparison with the other groups. However, ozone/oxygen mixture induced a significant stimulation in the enzymatic activity of CAT, SOD, and glutathione peroxidase, as well as reduced glutathione in relation with Sham and positive control groups. In this animal model of CRF, ozone

  7. Microglia P2Y6 receptor is related to Parkinson’s disease through neuroinflammatory process

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    Xiaodong Yang

    2017-02-01

    Full Text Available Abstract Background Microglia in the central nervous system (CNS were reported to play crucial role in neurodegeneration. Previous studies showed that P2Y6 receptor (P2Y6R mainly contributed to microglia activation and phagocytosis in CNS. However, the level of P2Y6R in Parkinson’s disease (PD patients is unclear. Therefore, we measured the level of P2Y6R in PD patients and speculated whether it could be a potential biomarker for PD. Given on the basis that P2Y6R was higher in PD patients, we further explored the mechanisms underlying P2Y6R in the pathogenesis of PD. Methods We tested the expression level of P2Y6R in the peripheral blood mononuclear cells (PBMCs among 145 PD patients, 170 healthy controls, and 30 multiple system atrophy (MSA patients. We also used a lipopolysaccharide (LPS-stimulated microglial cell culture model to investigate (i the effects of LPS on P2Y6R expression with western blot and RT-PCR, (ii the effects of LPS on UDP expression using HPLC, (iii the effects of UDP/P2Y6R signaling on cytokine expression using western blot, RT-PCR, and ELISA, and (iv the signaling pathways activated by the P2Y6R involved in the neuroinflammation. Results Expression levels of P2Y6R in PD patients were higher than healthy controls and MSA patients. P2Y6R could be a good biomarker of PD. P2Y6R was also upregulated in LPS-treated BV-2 cells and involved in proinflammatory cytokine release through an autocrine loop based on LPS-triggered UDP secretion and accelerated neuroinflammatory responses through the ERK1/2 pathway. Importantly, blocking UDP/P2Y6R signaling could reverse these pathological processes. Conclusions P2Y6R may be a potential clinical biomarker of PD. Blocking P2Y6R may be a potential therapeutic approach to the treatment of PD patients through inhibition of microglia-activated neuroinflammation.

  8. Key Aging-Associated Alterations in Primary Microglia Response to Beta-Amyloid Stimulation

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    Cláudia Caldeira

    2017-08-01

    Full Text Available Alzheimer’s disease (AD is characterized by a progressive cognitive decline and believed to be driven by the self-aggregation of amyloid-β (Aβ peptide into oligomers and fibrils that accumulate as senile plaques. It is widely accepted that microglia-mediated inflammation is a significant contributor to disease pathogenesis; however, different microglia phenotypes were identified along AD progression and excessive Aβ production was shown to dysregulate cell function. As so, the contribution of microglia to AD pathogenesis remains to be elucidated. In this study, we wondered if isolated microglia cultured for 16 days in vitro (DIV would react differentially from the 2 DIV cells upon treatment with 1000 nM Aβ1–42 for 24 h. No changes in cell viability were observed and morphometric alterations associated to microglia activation, such as volume increase and process shortening, were obvious in 2 DIV microglia, but less evident in 16 DIV cells. These cells showed lower phagocytic, migration and autophagic properties after Aβ treatment than the 2 DIV cultured microglia. Reduced phagocytosis may derive from increased CD33 expression, reduced triggering receptor expressed on myeloid cells 2 (TREM2 and milk fat globule-EGF factor 8 protein (MFG-E8 levels, which were mainly observed in 16 DIV cells. Activation of inflammatory mediators, such as high mobility group box 1 (HMGB1 and pro-inflammatory cytokines, as well as increased expression of Toll-like receptor 2 (TLR2, TLR4 and fractalkine/CX3C chemokine receptor 1 (CX3CR1 cell surface receptors were prominent in 2 DIV microglia, while elevation of matrix metalloproteinase 9 (MMP9 was marked in 16 DIV cells. Increased senescence-associated β-galactosidase (SA-β-gal and upregulated miR-146a expression that were observed in 16 DIV cells showed to increase by Aβ in 2 DIV microglia. Additionally, Aβ downregulated miR-155 and miR-124, and reduced the CD11b+ subpopulation in 2 DIV microglia, while

  9. The role of oxidative, inflammatory and neuroendocrinological systems during exercise stress in athletes: implications of antioxidant supplementation on physiological adaptation during intensified physical training.

    Science.gov (United States)

    Slattery, Katie; Bentley, David; Coutts, Aaron J

    2015-04-01

    During periods of intensified physical training, reactive oxygen species (ROS) release may exceed the protective capacity of the antioxidant system and lead to dysregulation within the inflammatory and neuroendocrinological systems. Consequently, the efficacy of exogenous antioxidant supplementation to maintain the oxidative balance in states of exercise stress has been widely investigated. The aim of this review was to (1) collate the findings of prior research on the effect of intensive physical training on oxidant-antioxidant balance; (2) summarise the influence of antioxidant supplementation on the reduction-oxidation signalling pathways involved in physiological adaptation; and (3) provide a synopsis on the interactions between the oxidative, inflammatory and neuroendocrinological response to exercise stimuli. Based on prior research, it is evident that ROS are an underlying aetiology in the adaptive process; however, the impact of antioxidant supplementation on physiological adaptation remains unclear. Equivocal results have been reported on the impact of antioxidant supplementation on exercise-induced gene expression. Further research is required to establish whether the interference of antioxidant supplementation consistently observed in animal-based and in vivo research extends to a practical sports setting. Moreover, the varied results reported within the literature may be due to the hormetic response of oxidative, inflammatory and neuroendocrinological systems to an exercise stimulus. The collective findings suggest that intensified physical training places substantial stress on the body, which can manifest as an adaptive or maladaptive physiological response. Additional research is required to determine the efficacy of antioxidant supplementation to minimise exercise-stress during intensive training and promote an adaptive state.

  10. A Distinct Population of Microglia Supports Adult Neurogenesis in the Subventricular Zone

    DEFF Research Database (Denmark)

    Ribeiro Xavier, Anna L.; Kress, Benjamin T.; Goldman, Steven A.

    2015-01-01

    found that microglia residing in the SVZ and adjacent rostral migratory stream (RMS) comprise a morphologically and antigenically distinct phenotype of immune effectors. Whereas exhibiting characteristics of alternatively activated microglia, the SVZ/RMS microglia were clearly distinguished by their low...... STATEMENT: Microglial cells are a specialized population of macrophages in the CNS, playing key roles as immune mediators. As integral components in the CNS, the microglia stand out for using the same mechanisms, phagocytosis and cytochemokine release, to promote homeostasis, synaptic pruning, and neural...... toward olfactory bulb layers. In addition to other unique populations residing in the SVZ niche, microglia display distinct morphofunctional properties that boost neuronal progenitor survival and migration in the mammalian brain....

  11. Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease

    Science.gov (United States)

    Baker, Christopher A.; Manuelidis, Laura

    2003-01-01

    Previous studies in Creutzfeldt-Jakob disease (CJD) have shown that myeloid cells in the periphery as well as derivative microglial cells in the brain are infectious. Microglia can show an activated phenotype before prion protein (PrP) pathology is detectable in brain, and isolated infectious microglia contain very little PrP. To find whether a set of inflammatory genes are significantly induced or suppressed with infection, we analyzed RNA from isolated microglia with relevant cDNA arrays, and identified 30 transcripts not previously examined in any transmissible spongiform encephalopathy. This CJD expression profile contrasted with that of uninfected microglia exposed to prototypic inflammatory stimuli such as lipopolysaccharide and IFN-, as well as PrP amyloid. These findings underscore inflammatory pathways evoked by the infectious agent in brain. Transcript profiles unique for CJD microglia and other myeloid cells provide opportunities for more sensitive preclinical diagnoses of infectious and noninfectious neurodegenerative diseases.

  12. Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury

    Science.gov (United States)

    Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2016-01-01

    Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516

  13. Exogenous spermidine is enhancing tomato tolerance to salinity-alkalinity stress by regulating chloroplast antioxidant system and chlorophyll metabolism.

    Science.gov (United States)

    Li, Jianming; Hu, Lipan; Zhang, Li; Pan, Xiongbo; Hu, Xiaohui

    2015-12-29

    capacities for responding to salinity-alkalinity stress. Exogenous spermidine triggers effective protection against damage induced by salinity-alkalinity stress in tomato seedlings, probably by maintaining chloroplast structural integrity and alleviating salinity-alkalinity-induced oxidative damage, most likely through regulation of chlorophyll metabolism and the enzymatic and non-enzymatic antioxidant systems in chloroplast. Exogenous spermidine also exerts positive effects at the transcription level, such as down-regulation of the expression of the chlorophyllase gene and up-regulation of the expression of the porphobilinogen deaminase gene.

  14. Dissecting the integrative antioxidant and redox systems in plant mitochondria. Effect of stress and S-nitrosylation.

    Directory of Open Access Journals (Sweden)

    Juan José Lázaro

    2013-11-01

    Full Text Available Mitochondrial respiration provides the energy needed to drive metabolic and transport processes in cells. Mitochondria are a significant site of reactive oxygen species (ROS production in plant cells, and redox-system components obey fine regulation mechanisms that are essential in protecting the mitochondrial integrity. In addition to ROS, there are compelling indications that nitric oxide (NO. can be generated in this organelle by both reductive and oxidative pathways. ROS and reactive nitrogen species (RNS play a key role in signaling but they can also be deleterious via oxidation of macromolecules. The high production of ROS obligates mitochondria to be provided with a set of ROS scavenging mechanisms. The first line of mitochondrial antioxidants is composed of superoxide dismutase and the enzymes of the ascorbate-glutathione cycle, which are not only able to scavenge ROS but also to repair cell damage and possibly serve as redox sensors. The dithiol-disulfide exchanges form independent signaling nodes and act as antioxidant defense mechanisms as well as sensor proteins modulating redox signaling during development and stress adaptation. The presence of thioredoxin (Trx, peroxiredoxin (Prx and sulfiredoxin (Srx in the mitochondria has been recently reported. Cumulative results obtained from studies in salt stress models have demonstrated that these redox proteins play a significant role in the establishment of salt tolerance. The Trx/Prx/Srx system may be subjected to a fine regulated mechanism involving post-translational modifications, among which S-glutathionylation and S-nitrosylation seem to exhibit a critical role that is just beginning to be understood. This review summarizes our current knowledge in antioxidative systems in plant mitochondria, their interrelationships, mechanisms of compensation and some unresolved questions, with special focus on their response to abiotic stress.

  15. Glutathione-induced drought stress tolerance in mung bean: coordinated roles of the antioxidant defence and methylglyoxal detoxification systems

    Science.gov (United States)

    Nahar, Kamrun; Hasanuzzaman, Mirza; Alam, Md. Mahabub; Fujita, Masayuki

    2015-01-01

    Drought is considered one of the most acute environmental stresses presently affecting agriculture. We studied the role of exogenous glutathione (GSH) in conferring drought stress tolerance in mung bean (Vigna radiata L. cv. Binamoog-1) seedlings by examining the antioxidant defence and methylglyoxal (MG) detoxification systems and physiological features. Six-day-old seedlings were exposed to drought stress (−0.7 MPa), induced by polyethylene glycol alone and in combination with GSH (1 mM) for 24 and 48 h. Drought stress decreased seedling dry weight and leaf area; resulted in oxidative stress as evidenced by histochemical detection of hydrogen peroxide (H2O2) and O2⋅− in the leaves; increased lipid peroxidation (malondialdehyde), reactive oxygen species like H2O2 content and O2⋅− generation rate and lipoxygenase activity; and increased the MG level. Drought decreased leaf succulence, leaf chlorophyll and relative water content (RWC); increased proline (Pro); decreased ascorbate (AsA); increased endogenous GSH and glutathione disulfide (GSSG) content; decreased the GSH/GSSG ratio; increased ascorbate peroxidase and glutathione S-transferase activities; and decreased the activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and catalase. The activities of glyoxalase I (Gly I) and glyoxalase II (Gly II) increased due to drought stress. In contrast to drought stress alone, exogenous GSH enhanced most of the components of the antioxidant and glyoxalase systems in drought-affected mung bean seedlings at 24 h, but GSH did not significantly affect AsA, Pro, RWC, leaf succulence and the activities of Gly I and DHAR after 48 h of stress. Thus, exogenous GSH supplementation with drought significantly enhanced the antioxidant components and successively reduced oxidative damage, and GSH up-regulated the glyoxalase system and reduced MG toxicity, which played a significant role in improving the physiological features and drought

  16. Influence of Aluminium Chloride on Antioxidant System in the Testis and Epididymis of Rats

    Directory of Open Access Journals (Sweden)

    Arumugam Kalaiselvi

    2014-03-01

    Full Text Available Background: In recent years, the use of chemicals in agriculture, industry, and public health has become so common that the environment is continuously contaminated by the toxic substance-like metals. Aluminum released due to anthropogenic activities such as mining and industrial uses. Aluminium has several industrial uses. The present study was designed to investigate the effect of aluminium chloride (AlCl3 on enzymatic and non-enzymatic antioxidants in the testis and epididymis of rats. Methods: Adult male rats were administered with aluminium chloride at two different doses, 50 mg and 100 mg/kg body weight, orally, daily for 45 days. At the end of the experimental period, the animals were sacrificed and their testis and the epididymis were removed. Antioxidant enzymes like catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GPx, glutathione reductase (GR, and glutathione-s-transferase (GST were assayed. Lipid peroxidation (LPO, vitamin C, and vitamin E levels were also determined. Results: Aluminium chloride administration had no effect on the bodyweight of the animals but the weight of the testis and epididymis was decreased. Almost all the antioxidant enzymes studied markedly diminished in the testis and epididymis of aluminium chloride treated animals. The non-enzymatic antioxidants, vitamin C and vitamin E, also declined. Lipid peroxidation, on the other hand, significantly increased. The influence was found to be more in 100 mg treated rats when compared to 50 mg treated rats. Conclusions: The present study suggests the reproductive toxicity of aluminium by inducing the oxidative stress in the testis and epididymis and possible interference in sperm production and further maturational processes.

  17. Cardioprotective and nonprotective regimens of chronic hypoxia diversely affect the myocardial antioxidant systems

    Czech Academy of Sciences Publication Activity Database

    Kašparová, D.; Neckář, Jan; Dabrowská, L.; Novotný, J.; Mráz, J.; Kolář, František; Žurmanová, J.

    2015-01-01

    Roč. 47, č. 12 (2015), s. 612-620 ISSN 1094-8341 R&D Projects: GA ČR(CZ) GAP303/12/1162; GA ČR(CZ) GA13-10267S Institutional support: RVO:67985823 Keywords : adaptation to hypoxia * cardioprotection * ischemia-reperfusion injury * oxidative stress * antioxidant defense Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.615, year: 2015

  18. Antioxidant systems are regulated by nitric oxide-mediated post-translational modifications (NO-PTMs

    Directory of Open Access Journals (Sweden)

    Juan Carlos Begara-Morales

    2016-02-01

    Full Text Available Nitric oxide (NO is a biological messenger that orchestrates a plethora of plant functions, mainly through post-translational modifications (PTMs such as S-nitrosylation or tyrosine nitration. In plants, hundreds of proteins have been identified as potential targets of these NO-PTMs under physiological and stress conditions indicating the relevance of NO in plant-signaling mechanisms. Among these NO protein targets, there are different antioxidant enzymes involved in the control of reactive oxygen species (ROS, such as H2O2, which is also a signal molecule. This highlights the close relationship between ROS/NO signaling pathways. The major plant antioxidant enzymes, including catalase, superoxide dismutases (SODs peroxiredoxins (Prx and all the enzymatic components of the ascorbate-glutathione (Asa-GSH cycle, have been shown to be modulated to different degrees by NO-PTMs. This mini-review will update the recent knowledge concerning the interaction of NO with these antioxidant enzymes, with a special focus on the components of the Asa-GSH cycle and their physiological relevance.

  19. Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct aspects of microglia proinflammatory transformation

    Directory of Open Access Journals (Sweden)

    Halleskog Carina

    2012-05-01

    Full Text Available Abstract Background WNT-5A signaling in the central nervous system is important for morphogenesis, neurogenesis and establishment of functional connectivity; the source of WNT-5A and its importance for cellular communication in the adult brain, however, are mainly unknown. We have previously investigated the inflammatory effects of WNT/β-catenin signaling in microglia in Alzheimer's disease. WNT-5A, however, generally recruits β-catenin-independent signaling. Thus, we aim here to characterize the role of WNT-5A and downstream signaling pathways for the inflammatory transformation of the brain's macrophages, the microglia. Methods Mouse brain sections were used for immunohistochemistry. Primary isolated microglia and astrocytes were employed to characterize the WNT-induced inflammatory transformation and underlying intracellular signaling pathways by immunoblotting, quantitative mRNA analysis, proliferation and invasion assays. Further, measurements of G protein activation by [γ-35 S]GTP binding, examination of calcium fluxes and cyclic AMP production were used to define intracellular signaling pathways. Results Astrocytes in the adult mouse brain express high levels of WNT-5A, which could serve as a novel astroglia-microglia communication pathway. The WNT-5A-induced proinflammatory microglia response is characterized by increased expression of inducible nitric oxide synthase, cyclooxygenase-2, cytokines, chemokines, enhanced invasive capacity and proliferation. Mapping of intracellular transduction pathways reveals that WNT-5A activates heterotrimeric Gi/o proteins to reduce cyclic AMP levels and to activate a Gi/o protein/phospholipase C/calcium-dependent protein kinase/extracellular signal-regulated kinase 1/2 (ERK1/2 axis. We show further that WNT-5A-induced ERK1/2 signaling is responsible for distinct aspects of the proinflammatory transformation, such as matrix metalloprotease 9/13 expression, invasion and proliferation. Conclusions

  20. RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems.

    Science.gov (United States)

    Shin, Daiha; Kim, Eun Hye; Lee, Jaewang; Roh, Jong-Lyel

    2017-10-01

    Reactivation of p53 and induction of tumor cell apoptosis (RITA) is a small molecule that blocks p53-MDM2 interaction, thereby reactivating p53 in tumors. RITA can induce exclusive apoptosis in cancer cells independently of the p53 pathway; however, the resistance of cancer cells remains a major drawback. Here, we found a novel resistance mechanism of RITA treatment and an effective combined treatment to overcome RITA resistance in head and neck cancer (HNC) cells. The effects of RITA and 3-methyladenine (3-MA) were tested in different HNC cell lines, including cisplatin-resistant and acquired RITA-resistant HNC cells. The effects of each drug alone and in combination were assessed by measuring cell viability, apoptosis, cell cycle, glutathione, reactive oxygen species, protein expression, genetic inhibition of p62 and Nrf2, and a mouse xenograft model of cisplatin-resistant HNC. RITA induced apoptosis of HNC cells at different levels without significantly inhibiting normal cell viability. Following RITA treatment, RITA-resistant HNC cells exhibited a sustained expression of other autophagy-related proteins, overexpressed p62, and displayed activation of the Keap1-Nrf2 antioxidant pathway. The autophagy inhibitor 3-MA sensitized resistant HNC cells to RITA treatment via the dual inhibition of molecules related to the autophagy and antioxidant systems. Silencing of the p62 gene augmented the combined effects. The effective antitumor activity of RITA plus 3-MA was also confirmed in vivo in mouse xenograft models transplanted with resistant HNC cells, showing increased oxidative stress and DNA damage. The results indicate that RITA plus 3-MA can help overcome RITA resistance in HNC cells. This study revealed a novel RITA resistant mechanism associated with the sustained induction of autophagy, p62 overexpression, and Keap1-Nrf2 antioxidant system activation. The combined treatment of RITA with the autophagy inhibitor 3-methyladenine overcomes RITA resistance via dual

  1. Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

    International Nuclear Information System (INIS)

    Stringari, James; Nunes, Adriana K.C.; Franco, Jeferson L.; Bohrer, Denise; Garcia, Solange C.; Dafre, Alcir L.; Milatovic, Dejan; Souza, Diogo O.; Rocha, Joao B.T.; Aschner, Michael; Farina, Marcelo

    2008-01-01

    During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/l, diluted in drinking water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PND) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F 2 -isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F 2 -isoprostanes levels at all time points. Significant negative correlations were found between F 2 -isoprostanes and GSH, as well as between F 2 -isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at

  2. A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion

    Directory of Open Access Journals (Sweden)

    Morrison Helena W

    2013-01-01

    Full Text Available Abstract Background Microglia cells continuously survey the healthy brain in a ramified morphology and, in response to injury, undergo progressive morphological and functional changes that encompass microglia activation. Although ideally positioned for immediate response to ischemic stroke (IS and reperfusion, their progressive morphological transformation into activated cells has not been quantified. In addition, it is not well understood if diverse microglia morphologies correlate to diverse microglia functions. As such, the dichotomous nature of these cells continues to confound our understanding of microglia-mediated injury after IS and reperfusion. The purpose of this study was to quantitatively characterize the spatiotemporal pattern of microglia morphology during the evolution of cerebral injury after IS and reperfusion. Methods Male C57Bl/6 mice were subjected to focal cerebral ischemia and periods of reperfusion (0, 8 and 24 h. The microglia process length/cell and number of endpoints/cell was quantified from immunofluorescent confocal images of brain regions using a skeleton analysis method developed for this study. Live cell morphology and process activity were measured from movies acquired in acute brain slices from GFP-CX3CR1 transgenic mice after IS and 24-h reperfusion. Regional CD11b and iNOS expressions were measured from confocal images and Western blot, respectively, to assess microglia proinflammatory function. Results Quantitative analysis reveals a significant spatiotemporal relationship between microglia morphology and evolving cerebral injury in the ipsilateral hemisphere after IS and reperfusion. Microglia were both hyper- and de-ramified in striatal and cortical brain regions (respectively after 60 min of focal cerebral ischemia. However, a de-ramified morphology was prominent when ischemia was coupled to reperfusion. Live microglia were de-ramified, and, in addition, process activity was severely blunted proximal to

  3. Dermal carotenoid level and kinetics after topical and systemic administration of antioxidants: enrichment strategies in a controlled in vivo study.

    Science.gov (United States)

    Darvin, Maxim E; Fluhr, Joachim W; Schanzer, Sabine; Richter, Heike; Patzelt, Alexa; Meinke, Martina C; Zastrow, Leonhard; Golz, Karin; Doucet, Olivier; Sterry, Wolfram; Lademann, Juergen

    2011-10-01

    High doses of sun-emitted UV-radiation induce reactive oxygen species (ROS) as major pro-oxidants thus inducing premature skin aging. The best prevention of the destructive action of free radicals in human skin is textile coverings, topical sunscreens and the development of a high antioxidative protective network. The effects of topical, systemic and combined application of antioxidants (AO) were investigated on human skin in vivo. Topical application of creams and systemic incorporation of tablets both containing AO was investigated in vivo by resonance Raman spectroscopy. Topical, systemic and combined AO-treatments induced a statistically significant increase of AO levels in human skin while placebo did not show any changes. The highest accumulation was induced by the combination of topical and systemic AO. Carotenoid-tablets combined with placebo-cream induced less carotenoid accumulation than carotenoid-tablets alone. Carotenoid levelling after the end of treatment lasted for around 2 weeks following the topical application of AOs, and up to 5 weeks after systemic administration, depending on the BMI of volunteers. Topically applied AO are stored in the SC for a short time only due to the rapid AO-depletion by desquamation, textile contact, washing and environmental stress. In contrast to topical application, the systemically applied carotenoids are stored in the body fat tissue and slowly released onto the skin surface with sweat and sebum. The combined topical and systemic application of AO represents an optimal form of protection of the AO-network. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Antioxidative system in the liver of rates subjected to combined irradiation injury

    International Nuclear Information System (INIS)

    Simovic, M.; Stanimirovic, D.; Ivanovic, L.; Markovic, M.; Letic-Gavrilovic, A.; Jovic, P.; Savic, J.; Spasic, M.; Saicic, Z.S.

    1991-01-01

    Until the Chernobyl nuclear plant catastrophe, exposure to radiation combined with other forms of injuries was usually considered as a hazard of nuclear war. The effect of combined irradiation injuries are often defined as the simultaneous effect of irradiation and another noxious stimulus. In the authors' opinion (1) one may talk about combined irradiation injuries (CII) only in the case when the general response of an organism to traumatization is the combination of biological reactions to at least two different etiologic noxious stimuli of which one is irradiation. One of the basic problems of combined injuries in general and CII in particular, is the syndrome of mutual aggravation (SMA) expressed through a very high (potentiated) lethality. The real mechanism(s) of this syndrome is still unknown. In our model of combined irradiation injury, potentiation of irradiation effect was smaller if animals were irradiated in the hypometabolic (open-quotes ebbclose quotes) compared to the hypermetabolic (open-quotes flowclose quotes) phase after thermal injury. Since the oxygen uptake is greater in the hypermetabolic phase the free radical production is also greater. On the other hand, the transition of hypometabolic to hypermetabolic phase could be analogous to a hypoxia/reoxygenation state. According to Granger et al. this state induces an increase in free radical production. When irradiation injury follows scalding it induces a new flux of free radicals. As a result the antioxidative defense of an organism could be overwhelmed and a disturbance of oxidative-antioxidative processes might occur. Thus, the authors suppose that overwhelmed antioxidative defense could be the reason for potentiated lethality in combined irradiation injury. 12 refs., 2 tabs

  5. The responses of antioxidant system in bitter melon, sponge gourd, and winter squash under flooding and chilling stresses

    Science.gov (United States)

    Do, Tuong Ha; Nguyen, Hoang Chinh; Lin, Kuan-Hung

    2018-04-01

    The objective of this paper was to review the responses of antioxidant system and physiological parameters of bitter melon (BM), sponge gourd (SG), and winter squash (WS) under waterlogged and low temperature conditions. The BM and SG plants were subjected to 0-72 h flooding treatments, and BM and WS plants were exposed to chilling at 12/7 °C (day/night) for 0-72 h. Different genotypes responded differently to environmental stress according to their various antioxidant system and physiological parameters. Increased ascorbate peroxidase (APX) and superoxide dismutase (SOD) activities provided SG and WS plants with increased waterlogging and chilling stress tolerance, respectively, compared to BM plants. The APX gene from SG and the SOD gene from WS were then cloned, and the regulation of APX and SOD gene expressions under flooding and chilling stress, respectively, were also measured. Increased expression of APX and SOD genes was accompanied by the increased activity of the enzyme involved in detoxifying reactive oxygen species (ROS) in response to those stresses. Both APX and SOD activities can be used for selecting BM lines with the best tolerances to water logging and chilling stresses.

  6. Polyphenolic composition and antioxidant capacity of legume based swards are affected by light intensity in a Mediterranean agroforestry system.

    Science.gov (United States)

    Re, Giovanni Antonio; Piluzza, Giovanna; Sanna, Federico; Molinu, Maria Giovanna; Sulas, Leonardo

    2018-06-01

    In Mediterranean grazed woodlands, microclimate changes induced by trees influence the growth and development of the understory, but very little is known about its polyphenolic composition in relation to light intensity. We investigated the bioactive compounds and antioxidant capacity of different legume-based swards and variations due to full sunlight and partial shade. The research was carried out in a cork oak agrosilvopastoral system in Sardinia. The highest values of DPPH reached 7 mmol TEAC 100 g -1 DW, total phenolics 67.1 g GAE kg -1 DW and total flavonoids 7.5 g CE kg -1 DW. Compared to full sunlight, partial shade reduced DPPH values by 29 and 42%, and the total phenolic content by 23 and 53% in 100% legume mixture and semi natural pasture. Twelve phenolic compounds were detected: chlorogenic acid in 80% legume mixture (partial shade) and verbascoside in pure sward of bladder clover (full sunlight) were the most abundant. Light intensity significantly affected antioxidant capacity, composition and levels of phenolic compounds. Our results provide new insights into the effects of light intensity on plant secondary metabolites from legume based swards, underlining the important functions provided by agroforestry systems. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Effect of antioxidants on x-ray induced DNA SSB and DSB in different cell systems

    International Nuclear Information System (INIS)

    Ramadu, Kadem

    1998-01-01

    The effect of x-ray radiation or antioxidants such as actinomycin D, cycloheximide and mitomycin C is studied on CHO, BHK and HeLa cells. X-ray radiation caused DNA single strand breaks (SSB) and double strand breaks (DSB) are prevented by cycloheximide and actinomycin-D. The DSB and SSB are significant in the case of x-ray radiation in combination with MMC, but different with actinomycin-D and cycloheximide in combination with x-ray radiation which causes less number of SSB and DSB. The ISC is observed more with x-ray radiation in combination with antioxidants mitomycin C (MMC) than that of cycloheximide and actinomycin-D, which individually causes inhibition of ISC induced by x-ray radiation. This observation proves that the MMC has an additive effect on x-ray induced ISC during cell proliferation. During cell proliferation, cell viability is observed with x-ray radiation and antioxidants which are dependent on the cell cycle phase. However, in the control cells, the initial Go-phase has shown negligible difference in percent cell viability thereby during S-phase gradual increase in the cell viability, and cell proliferation have been found to be stopped at G2+M-phase. On the contrary, cell viability and the extent of cell proliferation with x-ray radiation in combination with MMC have shown more damage (OH-damage) than is caused by x-ray radiation and MMC, separately. But, the fact is that actinomycin-D and cycloheximide act as antioxidants preventing thereby free radical formation and cell death, caused by x-ray radiation. During cell proliferation, cells observed from S and (G2+M) phase exhibit difference in cell viability in all the treatments alone and in combination. HeLa cells have been found insensitive to x-ray radiation and could be ascribed to the presence of glutathione transferase, which is less in CHO/BHK cell line. (author)

  8. Heat-induced regulation of antioxidant defense system and nutrient accumulation in hexaploid bread wheat (triticum aestivum l.)

    International Nuclear Information System (INIS)

    Zia, M.A.; Ashraf, M.; Akram, A.

    2014-01-01

    Ten cultivars (five registered S-24, Inqlab-91, Saher-2006, Fsd-2008, and Lasani, and five candidate cultivars P.B-18, M.P-65, S.H-20, AARI-10, and G.A-20) of spring wheat (Triticum aestivum L.) were examined for high temperature stress tolerance. Plants were grown in soil filled pots in the Botanical Garden of the Department of Botany University of Agriculture Faisalabad, Pakistan. Three different temperature regimes (30, 40 and 50 degree C) were applied at two different growth stages (tillering and boot) for three temperature durations 30, 60 and 90 min in a growth chamber. The leaf and root samples were collected after two weeks of temperature treatment and then analyzed for enzymatic and non-enzymatic antioxidants as well as inorganic nutrients (N, P, K+, Ca2+). At the end, data obtained were statistically analyzed to distinguish heat tolerant from non-tolerant wheat cultivars. After appraisal of growth, antioxidant defense system and uptake of nutrients it was found that cvs. S-24, Inqlab-91, Saher-2006, Fsd-2008, Lasani and G.A-20 exhibited better thermo-tolerance capabilities than the other wheat cultivars (P.B-18, M.P-65, S.H-20, AARI-10). Among the thermo-tolerant wheat cultivars, G.A-20 and Lasani were superior in maintaining shoot fresh weights and shoot length, high antioxidant activities and better nutrient uptake at both tillering and boot stages. The response of all cultivars to heat stress applied at the tillering stage or boot stage was almost the same. (author)

  9. Botanical Polyphenols Mitigate Microglial Activation and Microglia-Induced Neurotoxicity: Role of Cytosolic Phospholipase A2.

    Science.gov (United States)

    Chuang, Dennis Y; Simonyi, Agnes; Cui, Jiankun; Lubahn, Dennis B; Gu, Zezong; Sun, Grace Y

    2016-09-01

    Microglia play a significant role in the generation and propagation of oxidative/nitrosative stress, and are the basis of neuroinflammatory responses in the central nervous system. Upon stimulation by endotoxins such as lipopolysaccharides (LPS), these cells release pro-inflammatory factors which can exert harmful effects on surrounding neurons, leading to secondary neuronal damage and cell death. Our previous studies demonstrated the effects of botanical polyphenols to mitigate inflammatory responses induced by LPS, and highlighted an important role for cytosolic phospholipase A2 (cPLA2) upstream of the pro-inflammatory pathways (Chuang et al. in J Neuroinflammation 12(1):199, 2015. doi: 10.1186/s12974-015-0419-0 ). In this study, we investigate the action of botanical compounds and assess whether suppression of cPLA2 in microglia is involved in the neurotoxic effects on neurons. Differentiated SH-SY5Y neuroblastoma cells were used to test the neurotoxicity of conditioned medium from stimulated microglial cells, and WST-1 assay was used to assess for the cell viability of SH-SY5Y cells. Botanicals such as quercetin and honokiol (but not cyanidin-3-O-glucoside, 3CG) were effective in inhibiting LPS-induced nitric oxide (NO) production and phosphorylation of cPLA2. Conditioned medium from BV-2 cells stimulated with LPS or IFNγ caused neurotoxicity to SH-SY5Y cells. Decrease in cell viability could be ameliorated by pharmacological inhibitors for cPLA2 as well as by down-regulating cPLA2 with siRNA. Botanicals effective in inhibition of LPS-induced NO and cPLA2 phosphorylation were also effective in ameliorating microglial-induced neurotoxicity. Results demonstrated cytotoxic factors from activated microglial cells to cause damaging effects to neurons and potential use of botanical polyphenols to ameliorate the neurotoxic effects.

  10. High Morphologic Plasticity of Microglia/Macrophages Following Experimental Intracerebral Hemorrhage in Rats

    Directory of Open Access Journals (Sweden)

    Shu-Sheng Yang

    2016-07-01

    Full Text Available As current efforts have limited effects on the clinical outcome of intracerebral hemorrhage (ICH, the mechanisms including microglia/macrophages that involved inflammation need further investigation. Here, 0.4 units of collagenase VII were injected into the left caudate putamen (CPu to duplicate ICH rat models. In the brains of ICH rats, microglia/macrophages, the nearest cells to the hemorrhagic center, were observed as ameboid and Prussian-blue positive. Furthermore, the ameboid microglia/macrophages were differentiation (CD 68 and interleukin-1β (IL-1β positive, and neither CD206 nor chitinase3-like 3 (Ym1 positive, suggesting their strong abilities of phagocytosis and secretion of IL-1β. According to the distance to the hemorrhagic center, we selected four areas—I, II, III, and IV—to analyze the morphology of microglia/macrophages. The processes decreased successively from region I to region IV. Microglia/macrophages in region IV had no processes. The processes in region I were radially distributed, however, they showed obvious directivity towards the hemorrhagic center in regions II and III. Region III had the largest density of compactly arrayed microglia/macrophages. All these in vivo results present the high morphologic plasticity of microglia/macrophages and their functions in the pathogenesis of ICHs.

  11. Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease.

    Science.gov (United States)

    Davies, Danielle S; Ma, Jolande; Jegathees, Thuvarahan; Goldsbury, Claire

    2017-11-01

    Changes in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their gray matter coverage (arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52-98 years). This occurred during normal ageing and without microglia dystrophy or changes in cell density. There was a larger reduction in process length and arborized area in AD compared to aged-matched control microglia. In AD cases, on average, 49%-64% of microglia had discontinuous and/or punctate Iba1 labeled processes instead of continuous Iba1 distribution. Up to 16% of aged-matched control microglia displayed discontinuous or punctate features. There was no change in the density of microglial cell bodies in gray matter during ageing or AD. This demonstrates that human microglia show progressive cell process retraction without cell loss during ageing. Additional changes in microglia occur with AD including Iba1 protein puncta and discontinuity. We suggest that reduced microglial arborized area may be an aging-related correlate of AD in humans. These variations in microglial cells during ageing and in AD could reflect changes in neural-glial interactions which are emerging as key to mechanisms involved in ageing and neurodegenerative disease. © 2016 International Society of Neuropathology.

  12. Regulation of vacuolar H{sup +}-ATPase in microglia by RANKL

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    Serrano, Eric M.; Ricofort, Ryan D.; Zuo, Jian [Department of Orthodontics, University of Florida College of Dentistry, Gainesville, FL 32610 (United States); Ochotny, Noelle [Department of Pharmacology, University of Toronto, Toronto, Ont., Canada M5G 1G6 (Canada); Manolson, Morris F. [Faculty of Dentistry, University of Toronto, Toronto, Ont., Canada M5G 1G6 (Canada); Holliday, L. Shannon, E-mail: sholliday@dental.ufl.edu [Department of Orthodontics, University of Florida College of Dentistry, Gainesville, FL 32610 (United States); Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610 (United States)

    2009-11-06

    Vacuolar H{sup +}-ATPases (V-ATPases) are large electrogenic proton pumps composed of numerous subunits that play vital housekeeping roles in the acidification of compartments of the endocytic pathway. Additionally, V-ATPases play specialized roles in certain cell types, a capacity that is linked to cell type selective expression of isoforms of some of the subunits. We detected low levels of the a3 isoform of the a-subunit in mouse brain extracts. Examination of various brain-derived cell types by immunoblotting showed a3 was expressed in the N9 microglia cell line and in primary microglia, but not in other cell types. The expression of a3 in osteoclasts requires stimulation by Receptor Activator of Nuclear Factor {kappa}B-ligand (RANKL). We found that Receptor Activator of Nuclear Factor {kappa}B (RANK) was expressed by microglia. Stimulation of microglia with RANKL triggered increased expression of a3. V-ATPases in microglia were shown to bind microfilaments, and stimulation with RANKL increased the proportion of V-ATPase associated with the detergent-insoluble cytoskeletal fraction and with actin. In summary, microglia express the a3-subunit of V-ATPase. The expression of a3 and the interaction between V-ATPases and microfilaments was modulated by RANKL. These data suggest a novel molecular pathway for regulating microglia.

  13. RAGE-Specific Inhibitor FPS-ZM1 Attenuates AGEs-Induced Neuroinflammation and Oxidative Stress in Rat Primary Microglia.

    Science.gov (United States)

    Shen, Chao; Ma, Yingjuan; Zeng, Ziling; Yin, Qingqing; Hong, Yan; Hou, Xunyao; Liu, Xueping

    2017-10-01

    Advanced glycation end products (AGEs) enhance microglial activation and intensify the inflammatory response and oxidative stress in the brain. This process may occur due to direct cytotoxicity or interacting with AGEs receptors (RAGE), which are expressed on the surface of microglia. FPS-ZM1 is a high-affinity but nontoxic RAGE-specific inhibitor that has been recently shown to attenuate the Aβ-induced inflammatory response by blocking the ligation of Aβ to RAGE. In this study, we further investigated the effect of FPS-ZM1 on the AGEs/RAGE interaction and downstream elevation of neuroinflammation and oxidative stress in primary microglia cells. The results suggested that FPS-ZM1 significantly suppressed AGEs-induced RAGE overexpression, RAGE-dependent microglial activation, nuclear translocation of nuclear factor kappaB p65 (NF-κB p65), and the expression of downstream inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) and inducible nitric oxide synthase (iNOS)/nitric oxide (NO). Furthermore, FPS-ZM1 attenuated AGEs-stimulated NADPH oxidase (NOX) activation and reactive oxygen species (ROS) expression. Finally, FPS-ZM1 elevated the levels of transcription factors nuclear-factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1), as well as decreased antioxidant capacity and increased production of oxidative species. Our results suggest that FPS-ZM1 may be neuroprotective through attenuating microglial activation, oxidative stress and inflammation by blocking RAGE.

  14. Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis.

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    Luyan Guo

    Full Text Available Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9 and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS, tumor necrosis factor-α (TNF-α and monocyte chemoattractant protein-1 (MCP-1. HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K(+ current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K(+ channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K(+ channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K(+ current.

  15. Modulation of endogenous antioxidant system by wine polyphenols in human disease.

    Science.gov (United States)

    Rodrigo, Ramón; Miranda, Andrés; Vergara, Leonardo

    2011-02-20

    Numerous studies indicate that moderate red wine consumption is associated with a protective effect against all-cause mortality. Since oxidative stress constitutes a unifying mechanism of injury of many types of disease processes, it should be expected that polyphenolic antioxidants account for this beneficial effect. Nevertheless, beyond the well-known antioxidant properties of these compounds, they may exert several other protective mechanisms. Indeed, the overall protective effect of polyphenols is due to their large array of biological actions, such as free radical-scavenging, metal chelation, enzyme modulation, cell signalling pathways modulation and gene expression effects, among others. Wine possesses a variety of polyphenols, being resveratrol its most outstanding representative, due to its pleiotropic biological properties. The presence of ethanol in wine aids to polyphenol absorption, thereby contributing to their bioavailability. Before absorption, polyphenols must be hydrolyzed by intestinal enzymes or by colonic microflora. Then, they undergo intestinal and liver metabolism. There have been no reported polyphenol adverse effects derived from intakes currently associated with the normal diet. However, supplements for health-protection should be cautiously used as no level definition has been given to make sure the dose is safe. The role of oxidative stress and the beneficial effects of wine polyphenols against cardiovascular, cancer, diabetes, microbial, inflammatory, neurodegenerative and kidney diseases and ageing are reviewed. Future large scale randomized clinical trials should be conducted to fully establish the therapeutic use of each individual wine polyphenol against human disease. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Effect of Artemisia absinthium essential oil on antioxidative systems of broiler's liver

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    Kostadinović Ljiljana M.

    2014-01-01

    Full Text Available The effect of Artemisia absinthium essential oil (AAEO on enzymatic activity of super-oxide-dismutase (SOD, glutathione-peroxidase (GSHPx, glutathione-reductase (GR, peroxidase (POD, xantine-oxidase (XOD and non-enzymatic (content of lipid peroxides (LPx and gluthathione (GSH antioxidative status of broilers infected with mixture of oocysts of Eimeria tenella, Eimeria mitis and Eimeria necatrix in comparison to coccidiostat salinomycin was investigated. The in vivo investigation were carried out on 120 Arbor acres broilers of both sexes. Broilers were randomly distributed into four groups. Group A was uninfected and untreated; group B was infected and was kept untreated; group C preventively received coccidiostatic salinomycin in quantity of 60 mg/kg of feed and was inoculated with coccidia species at 21st day-of-age and group D received in feed AAEO in quantity of 3 g/kg and was infected with Eimeria oocysts at 21st day-of-age. Livers were collected for the subsequent evaluation of antioxidative status. It was concluded that AAEO added in feed for broilers prevented the development of coccidia oocysts and therefore it can be used as prophylactic feed additive.

  17. Optimal binary solvent extraction system for phenolic antioxidants from mengkudu (Morinda citrifolia) fruit.

    Science.gov (United States)

    Thoo, Yin Yin; Ho, Swee Kheng; Abas, Faridah; Lai, Oi Ming; Ho, Chun Wai; Tan, Chin Ping

    2013-06-14

    Antioxidants have been widely used in the food industry to enhance product quality by preventing oxidation of susceptible substances. This work was carried out to maximise the recovery of total phenolic content (TPC), total flavonoid content (TFC), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical-scavenging capacity and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging capacity from Morinda citrifolia fruit via modification of the ethanol concentration, extraction time and extraction temperature at minimal processing cost. The optimised conditions yielded values of 881.57 ± 17.74 mg GAE/100 g DW for TPC, 552.53 ± 34.16 mg CE/100 g DW for TFC, 799.20 ± 2.97 µmol TEAC/100 g DW for ABTS and 2,317.01 ± 18.13 µmol TEAC/100 g DW for DPPH were 75% ethanol, 40 min of time and 57 °C. The four responses did not differ significantly (p > 0.05) from predicted values, indicating that models obtained are suitable to the optimisation of extraction conditions for phenolics from M. citrifolia. The relative amounts of flavonoids were 0.784 ± 0.01 mg quercetin/g of extract and 1.021 ± 0.04 mg rutin/g of extract. On the basis of the results obtained, M. citrifolia extract can be used as a valuable bioactive source of natural antioxidants.

  18. Hypoxia tolerance and antioxidant defense system of juvenile jumbo squids in oxygen minimum zones

    Science.gov (United States)

    Trübenbach, Katja; Teixeira, Tatiana; Diniz, Mário; Rosa, Rui

    2013-10-01

    Jumbo squid (Dosidicus gigas) is a large oceanic squid endemic off the Eastern Tropical Pacific that undertakes diel vertical migrations into mesopelagic oxygen minimum zones. One of the expected physiological effects of such migration is the generation of reactive oxygen species (ROS) at the surface, promoted by the transition between hypoxia and reoxygenation states. The aim of this study was to investigate the energy expenditure rates and the antioxidant stress strategies of juvenile D. gigas under normoxia and hypoxia, namely by quantifying oxygen consumption rates, antioxidant enzyme activities [including superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST)], heat shock protein expression (Hsp70/Hsc70), and lipid peroxidation [malondialdehyde (MDA) levels]. A high significant decrease (68%) in squid's metabolic rates was observed during hypoxia (p0.05), with the latter indicating no enhancement of lipid peroxidation (i.e. cellular damage) at the warmer and normoxic surface waters. The understanding of such physiological strategies that are linked to oxygen deprivation and reoxygenation phases may provide valuable information about how this species is quickly responding to the impacts of environmental stressors coupled with global climate change.

  19. Oxidative stress and antioxidative systems: recipes for successful data collection and interpretation.

    Science.gov (United States)

    Noctor, Graham; Mhamdi, Amna; Foyer, Christine H

    2016-05-01

    Oxidative stress and reactive oxygen species (ROS) are common to many fundamental responses of plants. Enormous and ever-growing interest has focused on this research area, leading to an extensive literature that documents the tremendous progress made in recent years. As in other areas of plant biology, advances have been greatly facilitated by developments in genomics-dependent technologies and the application of interdisciplinary techniques that generate information at multiple levels. At the same time, advances in understanding ROS are fundamentally reliant on the use of biochemical and cell biology techniques that are specific to the study of oxidative stress. It is therefore timely to revisit these approaches with the aim of providing a guide to convenient methods and assisting interested researchers in avoiding potential pitfalls. Our critical overview of currently popular methodologies includes a detailed discussion of approaches used to generate oxidative stress, measurements of ROS themselves, determination of major antioxidant metabolites, assays of antioxidative enzymes and marker transcripts for oxidative stress. We consider the applicability of metabolomics, proteomics and transcriptomics approaches and discuss markers such as damage to DNA and RNA. Our discussion of current methodologies is firmly anchored to future technological developments within this popular research field. © 2016 John Wiley & Sons Ltd.

  20. Effects of Platycodin D on Reflux Esophagitis due to Modulation of Antioxidant Defense Systems

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    Su-Yeon Cho

    2018-01-01

    Full Text Available Aims. The effects of platycodin D (PD pretreatment were examined in reflux esophagitis (RE induced rats. Methods. Sham, control, and omeprazole (OMP group were pretreated with distilled water or OMP as a reference, respectively, and PD pretreated groups were given 3 different PD doses once a day for 7 days. One hour after last pretreatment, RE was induced by ligation of the forestomach and pylorus. At 8 h after operation, all animals were sacrificed. Results. PD showed significant dose-dependent reduction of gastric secretion, myeloperoxidase activity, and RE lesion areas of esophagus and stomach mucosa. There was a reduction of lipid peroxidation in 2 doses of PD groups and elevation of antioxidant enzyme activity in all PD groups. Gastric hexose and sialic acid were significantly increased in PD groups, while collagen was reduced. Plasma histamine levels were significantly reduced in all PD groups, but not in the OMP group. Total invasive lesion sizes of esophagus and gastric fundus were significantly decreased in all PD groups. Thicknesses in esophagus of all PD groups were significantly decreased and thicknesses of funds were significantly increased except lowest PD dose. Conclusions. Therapeutic effects of PD on the esophageal and gastric lesions were shown in RE induced rats dose-dependently. The PD pretreatment had significant antioxidant effects with regulation of histamine levels. This study provides useful information regarding the effectiveness of the drug for RE and further novel drug discovery using natural herbal products.

  1. Toll-like receptor 9 is required for opioid-induced microglia apoptosis.

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    Lei He

    2011-04-01

    Full Text Available Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. However, the underlying mechanism by which microglia in response to opioids remains largely unknown. Here we show that morphine induces the expression of Toll-like receptor 9 (TLR9, a key mediator of innate immunity and inflammation. Interestingly, TLR9 deficiency significantly inhibited morphine-induced apoptosis in microglia. Similar results were obtained when endogenous TLR9 expression was suppressed by the TLR9 inhibitor CpGODN. Inhibition of p38 MAPK by its specific inhibitor SB203580 attenuated morphine-induced microglia apoptosis in wild type microglia. Morphine caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type microglia, but not in TLR9 deficient microglia. In addition, morphine treatment failed to induce an increased levels of phosphorylated p38 MAPK and MAP kinase kinase 3/6 (MKK3/6, the upstream MAPK kinase of p38 MAPK, in either TLR9 deficient or µ-opioid receptor (µOR deficient primary microglia, suggesting an involvement of MAPK and µOR in morphine-mediated TLR9 signaling. Moreover, morphine-induced TLR9 expression and microglia apoptosis appears to require μOR. Collectively, these results reveal that opioids prime microglia to undergo apoptosis through TLR9 and µOR as well. Taken together, our data suggest that inhibition of TLR9 and/or blockage of µOR is capable of preventing opioid-induced brain damage.

  2. Selective Estrogen Receptor Modulators regulate reactive microglia after penetrating brain injury

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    George E. Barreto

    2014-06-01

    Full Text Available Following brain injury, microglia assume a reactive-like state and secrete pro-inflammatory molecules that can potentiate damage. A therapeutic strategy that may limit microgliosis is of potential interest. In this context, selective estrogen receptor modulators, such as raloxifene and tamoxifen, are known to reduce microglia activation induced by neuroinflammatory stimuli in young animals. In the present study, we have assessed whether raloxifene and tamoxifen are able to affect microglia activation after brain injury in young and aged animals in time points relevant to clinics, which is hours after brain trauma. Volume fraction of MHC-II+ microglia was estimated according to the point-counting method of Weibel within a distance of 350 μm from the lateral border of the wound, and cellular morphology was measured by fractal analysis. Two groups of animals were studied: 1 young rats, ovariectomized at 2 months of age; and 2 aged rats, ovariectomized at 18 months of age. Fifteen days after ovariectomy animals received a stab wound brain injury and the treatment with estrogenic compounds. Our findings indicate that raloxifene and tamoxifen reduced microglia activation in both young and aged animals. Although the volume fraction of reactive microglia was found lower in aged animals, this was accompanied by important changes in cell morphology, where aged microglia assume a bushier and hyperplasic aspect when compared to young microglia. These data suggest that early regulation of microglia activation provides a mechanism by which SERMs may exert a neuroprotective effect in the setting of a brain trauma.

  3. Involvement of microglia activation in the lead induced long-term potentiation impairment.

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    Ming-Chao Liu

    Full Text Available Exposure of Lead (Pb, a known neurotoxicant, can impair spatial learning and memory probably via impairing the hippocampal long-term potentiation (LTP as well as hippocampal neuronal injury. Activation of hippocampal microglia also impairs spatial learning and memory. Thus, we raised the hypothesis that activation of microglia is involved in the Pb exposure induced hippocampal LTP impairment and neuronal injury. To test this hypothesis and clarify its underlying mechanisms, we investigated the Pb-exposure on the microglia activation, cytokine release, hippocampal LTP level as well as neuronal injury in in vivo or in vitro model. The changes of these parameters were also observed after pretreatment with minocycline, a microglia activation inhibitor. Long-term low dose Pb exposure (100 ppm for 8 weeks caused significant reduction of LTP in acute slice preparations, meanwhile, such treatment also significantly increased hippocampal microglia activation as well as neuronal injury. In vitro Pb-exposure also induced significantly increase of microglia activation, up-regulate the release of cytokines including tumor necrosis factor-alpha (TNF-α, interleukin-1β (IL-1β and inducible nitric oxide synthase (iNOS in microglia culture alone as well as neuronal injury in the co-culture with hippocampal neurons. Inhibiting the microglia activation with minocycline significantly reversed the above-mentioned Pb-exposure induced changes. Our results showed that Pb can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, these proinflammatory factors may cause hippocampal neuronal injury as well as LTP deficits.

  4. Effect of Calcium and Potassium on Antioxidant System of Vicia faba L. Under Cadmium Stress

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    Hayssam M. Ali

    2012-05-01

    Full Text Available Cadmium (Cd in soil poses a major threat to plant growth and productivity. In the present experiment, we studied the effect of calcium (Ca2+ and/or potassium (K+ on the antioxidant system, accumulation of proline (Pro, malondialdehyde (MDA, and content of photosynthetic pigments, cadmium (Cd and nutrients, i.e., Ca2+ and K+ in leaf of Vicia faba L. (cv. TARA under Cd stress. Plants grown in the presence of Cd exhibited reduced growth traits [root length (RL plant−1, shoot length (SL plant−1, root fresh weight (RFW plant−1, shoot fresh weight (SFW plant−1, root dry weight (RDW plant−1 and shoot dry weight (SDW plant−1] and concentration of Ca2+, K+, Chlorophyll (Chl a and Chl b content, except content of MDA, Cd and (Pro. The antioxidant enzymes [peroxidase (POD and superoxide dismutase (SOD] slightly increased as compared to control under Cd stress. However, a significant improvement was observed in all growth traits and content of Ca2+, K+, Chl a, Chl b ,Pro and activity of antioxidant enzymes catalase (CAT, POD and SOD in plants subjected to Ca2+ and/or K+. The maximum alleviating effect was recorded in the plants grown in medium containing Ca2+ and K+ together. This study indicates that the application of Ca2+ and/or K+ had a significant and synergistic effect on plant growth. Also, application of Ca2+ and/or K+ was highly effective against the toxicity of Cd by improving activity of antioxidant enzymes and solute that led to the enhanced plant growth of faba bean plants.

  5. MICROGLIA ACTIVATION AS A BIOMARKER FOR TRAUMATIC BRAIN INJURY

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    Diana G Hernadez-Ontiveros

    2013-03-01

    Full Text Available Traumatic brain injury (TBI has become the signature wound of wars in Afghanistan and Iraq. Injury may result from a mechanical force, a rapid acceleration-deceleration movement, or a blast wave. A cascade of secondary cell death events ensues after the initial injury. In particular, multiple inflammatory responses accompany TBI. A series of inflammatory cytokines and chemokines spreads to normal brain areas juxtaposed to the core impacted tissue. Among the repertoire of immune cells involved, microglia is a key player in propagating inflammation to tissues neighboring the core site of injury. Neuroprotective drug trials in TBI have failed, likely due to their sole focus on abrogating neuronal cell death and ignoring the microglia response despite these inflammatory cells’ detrimental effects on the brain. Another relevant point to consider is the veracity of results of animal experiments due to deficiencies in experimental design, such as incomplete or inadequate method description, data misinterpretation and reporting may introduce bias and give false-positive results. Thus, scientific publications should follow strict guidelines that include randomization, blinding, sample-size estimation and accurate handling of all data (Landis et al., 2012. A prolonged state of inflammation after brain injury may linger for years and predispose patients to develop other neurological disorders, such as Alzheimer’s disease. TBI patients display progressive and long-lasting impairments in their physical, cognitive, behavioral, and social performance. Here, we discuss inflammatory mechanisms that accompany TBI in an effort to increase our understanding of the dynamic pathological condition as the disease evolves over time and begin to translate these findings for defining new and existing inflammation-based biomarkers and treatments for TBI.

  6. Changes in Antioxidant Defense System Using Different Lipid Emulsions in Parenteral Nutrition in Children after Hematopoietic Stem Cell Transplantation

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    María Auxiliadora Baena-Gómez

    2015-08-01

    Full Text Available Background: Traditionally, lipids used in parenteral nutrition (PN are based on ω-6 fatty acid-rich vegetable oils, such as soybean oil, with potential adverse effects involving oxidative stress. Methods: We evaluated the antioxidant defense system in children, after hematopoietic stem cell transplantation (HSCT, who were randomized to use a lipid emulsion with fish oil or soybean oil. Blood samples at baseline, at 10 days, and at the end of the PN were taken to analyze plasma retinol, α-tocopherol, β-carotene, coenzyme Q9 and coenzyme Q10 levels, and catalase (CAT, glutathione reductase (GR, glutathione peroxidase (GPOX, and superoxide dismutase (SOD levels in lysed erythrocytes. Results: An increase in plasma α-tocopherol levels in the group of patients receiving the fish oil-containing emulsion (FO compared with the group receiving the soybean emulsion was observed at day 10 of PN. Concurrently, plasma α-tocopherol increased in the FO group and β-carotene decreased in both groups at day 10 compared with baseline levels, being more significant in the group receiving the FO emulsion. Conclusion: FO-containing emulsions in PN could improve the antioxidant profile by increasing levels of α-tocopherol in children after HSCT who are at higher risk of suffering oxidative stress and metabolic disorders.

  7. Modulation of the Antioxidant System Efficacy in Irradiated Rats Supplemented with Vitamin B12 cobalamin and Folic Acid

    International Nuclear Information System (INIS)

    Omran, M.F.; Abu-Zied, N.M.

    2006-01-01

    The present study has been performed to investigate the possible curative and protective role of supplemented vitamin B 12 and folic acid in the irradiation induced changes in certain biochemical parameters in hepatic tissue and blood. The biochemical analysis was done at one and fourteen days post irradiation. The data revealed serious effects of radiation exposure on the membrane integrity as reflected by increased serum potassium associated with decreased sodium levels. Oxidation of lipid and protein with antioxidant disorders were recorded after radiation exposure as reflected by increased contents of carbonyl and Gamma glutamyl transferase. The results showed significant increase in the level of lipid peroxide product (malonaldehyde) and significant decrease in the level of antioxidant defense system (glutathione, glutathione peroxidase, super oxid dismutase, catalase and glucose-6-phospate dehydrogenase) after one and fourteen day's supplementation with vitamin B 12 and folic acid. Supplemented of vitamin B 12 and folic acid before radiation exposure attenuated the harmful effects of irradiation on the most chosen parameters. The beneficial role of supplemented vitamin B 12 and folic acid may be related to its ability in quenching free radicals scavenging reactive oxygen species and improving regeneration in the biological tissues

  8. Effects of two different high doses of irradiation on antioxidant system in the liver of guinea pigs.

    Science.gov (United States)

    Guney, Yildiz; Bukan, Neslihan; Dizman, Aysen; Hicsonmez, Ayse; Bilgihan, Ayse

    2004-03-01

    To examine the state of the oxidant-antioxidant system in the liver of guinea pig caused by high doses of ionizing radiation in the early period. The research was carried out on guinea pigs irradiated with the doses of 8 Gy (group 2) or 15 Gy (group 3) (single dose/whole body) in comparison with control group (group 1). The levels of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and the levels of selenium in the liver were measured. TBARS levels in the irradiated animals were markedly higher than those in controls. In group 3, GSH levels and GSH-Px activity were significantly increased while activity of SOD and CAT were significantly decreased compared to groups 1 and 2. Liver selenium levels were not influenced by irradiation. The data have shown that gamma-irradiation at the doses of 8 Gy or 15 Gy results in significant increase in free radical formation while antioxidant enzymes were affected only at a dose of 15 Gy.

  9. Antioxidant Properties of Probiotic Bacteria.

    Science.gov (United States)

    Wang, Yang; Wu, Yanping; Wang, Yuanyuan; Xu, Han; Mei, Xiaoqiang; Yu, Dongyou; Wang, Yibing; Li, Weifen

    2017-05-19

    Oxidative stress defines a condition in which the prooxidant-antioxidant balance in the cell is disturbed, resulting in DNA hydroxylation, protein denaturation, lipid peroxidation, and apoptosis, ultimately compromising cells' viability. Probiotics have been known for many beneficial health effects, and the consumption of probiotics alone or in food shows that strain-specific probiotics can present antioxidant activity and reduce damages caused by oxidation. However, the oxidation-resistant ability of probiotics, especially the underling mechanisms, is not properly understood. In this view, there is interest to figure out the antioxidant property of probiotics and summarize the mode of action of probiotic bacteria in antioxidation. Therefore, in the present paper, the antioxidant mechanisms of probiotics have been reviewed in terms of their ability to improve the antioxidant system and their ability to decrease radical generation. Since in recent years, oxidative stress has been associated with an altered gut microbiota, the effects of probiotics on intestinal flora composition are also elaborated.

  10. [Effects of melaxen and valdoxan on the activity of glutathione antioxidant system and NADPH-producing enzymes in rat heart under experimental hyperthyroidism conditions].

    Science.gov (United States)

    Gorbenko, M V; Popova, T N; Shul'gin, K K; Popov, S S

    2013-01-01

    The effects of melaxen and valdoxan on the activity of glutathione antioxidant system and some NADPH-producing enzymes have been studied under conditions of experimental hyperthyroidism in rat heart. Under the action of these drugs, reduced glutathione (GSH) content increased as compared to values observed under the conditions of pathology. It has been established that the activities of glutathione reductase (GR), glutathione peroxidase (GP), glucose-6-phosphate dehydrogenase, and NADP isocitrate dehydrogenase (increased under pathological conditions) change toward the intact control values upon the introduction of both drugs. The influence of melaxen and valdoxan, capable of producing antioxidant effect, leads apparently to the inhibition of free-radical oxidation processes and, as a consequence, the reduction of mobilization degree of the glutathione antioxidant system.

  11. Response of antioxidant system of tomato to water deficit stress and its interaction with ascorbic acid

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    Fatemeh Daneshmand

    2014-03-01

    Full Text Available Environmental stresses including water deficit stress may produce oxidants such as reactive oxygen species that damage the membrane structure in plants. Among the antioxidants, ascorbic acid has a critical role in the cell and scavenges reactive oxygen species. In this research, effects of ascorbic acid at two levels (0 and 10 mM and water deficit stress based on 3 levels of field capacity (100, 60 and 30% were studied in tomato plants. Both levels of stress increased lipid peroxidation, reduced the amount of ascorbic acid and glutathione and increased the activity of enzymes superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, guaiacol peroxidase and reduced the growth parameters. Ascorbic acid treatment, reduced lipid peroxidation, increased ascorbic acid and glutathione levels and decreased the activity of superoxide dismutase, catalase, ascorbate peroxidase, glutathione peroxidase and guaiacol peroxidase and positive effects of ascorbic acid treatment appeared to improve the plant growth parameters.

  12. Involvement of Antioxidative Defense System in Rice Seedlings Exposed to Aluminum Toxicity and Phosphorus Deficiency

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    Tian-rong GUO

    2012-09-01

    Full Text Available Plants growing in acid soils may suffer both phosphorus (P deficiency and aluminum (Al toxicity. Hydroponic experiments were undertaken to assess the single and combination effects of Al toxicity and low P stress on seedling growth, chlorophyll and proline contents, antioxidative response and lipid peroxidation of two rice genotypes (Yongyou 8 and Xiushui 132 differing in Al tolerance. Al toxicity and P deficiency both inhibited rice seedling growth. The development of toxic symptoms was characterized by reduced chlorophyll content, increased proline and malondialdehyde contents in both roots and leaves, and increased peroxidase and superoxide dismutase activities in roots, but decreased in leaves. The stress condition induced more severe growth inhibition and oxidative stress in Yongyou 8, and Xiushui 132 showed higher tolerance to both Al toxicity and P deficiency. P deficiency aggravated Al toxicity to plant growth and induced more severe lipid peroxidation.

  13. Edible solid lipid nanoparticles (SLN as carrier system for antioxidants of different lipophilicity.

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    Kathleen Oehlke

    Full Text Available Ferulic acid (FA and tocopherol (Toc loaded solid lipid nanoparticles (SLN were prepared by a hot homogenisation method. The particle size distribution, zeta potential and melting behaviour of the SLN as well as the stability, encapsulation efficiency and radical scavenging activity of FA and Toc in the SLN were analysed. The different formulations containing up to 2.8 mg g-1 of FA or Toc were stable during at least 15 weeks of storage at room temperature. Despite partial degradation and / or release of FA and Toc during storage, significant radical scavenging activity was maintained. DSC measurements and radical scavenging tests after different time periods revealed that the re-structuring of the lipid matrix was connected to the enhanced antioxidant activity of Toc but did not affect the activity of FA.

  14. Effect of soil herbicides on the antioxidant system of maize vegetative organs during ontogenesis

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    I.P. Grigoryuk

    2016-06-01

    Full Text Available The impact of soil herbicides Harnes, Frontier and Merlin on the activity of enzymes superoxid dismutase (SOD, EC 1.15.1.1, catalase (CAT, EC 1.11.1.6, and benzidine peroxidase (POD, EC 1.11.1.7 in maize (Zea mays L.; cultivar Kadr 267 MV roots and leaves was studied in the field experiment. It was established that the adaptation of maize plants to the herbicides treatment was accompanied by significant activation of antioxidant enzymes both in roots (39%, 57%, and 67% above control level and leaves (50%, 64%, and 77% above control, respectively during different vegetation stages (shoots emergence; 3–5 leaves phase; florescence. The herbicides-induced changes of enzymes activity high correlated with ontogenetic dynamics of control plants activity: r = 0.98 for SOD; r = 0.96 for POD; r = 0.98 for CAT.

  15. The antioxidative response system in Glycine max (L.) Merr. exposed to Deltamethrin, a synthetic pyrethroid insecticide

    International Nuclear Information System (INIS)

    Bashir, Fozia; Mahmooduzzafar; Siddiqi, T.O.; Iqbal, Muhammad

    2007-01-01

    Forty-five-day-old plants of Glycine max (soybean) were exposed to several Deltamethrin (synthetic pyrethroid insecticide) concentrations (0.00 %, 0.05 %, 0.10 %, 0.15 % and 0.20 %) through foliar spray in the field conditions. In the treated plants, as observed at the pre-flowering (10 DAT), flowering (45 DAT) and post-flowering (70 DAT) stages, lipid peroxidation, proline content and total glutathione content increased, whereas the total ascorbate content decreased, as compared with the control. Among the enzymatic antioxidants, activity of superoxide dismutase, ascorbate peroxidase and glutathione reductase increased significantly whereas that of catalase declined markedly in relation to increasing concentration of Deltamethrin applied. The changes observed were dose-dependent, showing a strong correlation with the degree of treatment. - The Deltamethrin-induced oxidative stress alters the ascorbate-glutathione cycle in Glycine max

  16. Nrf2 and regulation of the antioxidant system in the Antarctic silverfish, Pleuragramma antarctica: Adaptation to environmental changes of pro-oxidant pressure.

    Science.gov (United States)

    Giuliani, Maria Elisa; Benedetti, Maura; Nigro, Marco; Regoli, Francesco

    2017-08-01

    Despite the key importance of Nrf2-Keap1 in regulating antioxidant system in vertebrates, this system is still poorly investigated in marine species. The present study focused on the Antarctic silverfish Pleuragramma antarctica which, during the final phases of embryo development in platelet ice, is challenged by a sudden enhancement of environmental oxidative conditions associated to ice melting. Partial coding sequences were identified for Nrf2, its repressor Keap1 and for typical Nrf2-target antioxidant genes, like catalase, glutathione peroxidase isoform 1 and Cu/Zn-dependent superoxide dismutase. Compared to temperate homologues, the protein sequences showed an elevated conservation of amino acids essential for catalytic functions, while a few specific substitutions in non-essential regions may represent a molecular adaptation to improve flexibility and accessibility to active site at cold temperatures. The role of the Nrf2-Keap1 pathway in modulating the activation of antioxidant defences was demonstrated at both transcriptional and functional levels with a clear temporal increase of antioxidant protection in embryos before the hatching. Such findings confirm the importance of Nrf2 and highlight regulation of antioxidants as an adaptive strategy in P. antarctica to protect the early life stages toward the environmental changes of pro-oxidant pressure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Amelioration of Heat Stress Induced Disturbances of Antioxidant Defense System in Chicken by Brahma Rasayana

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    V. Ramnath

    2008-01-01

    Full Text Available Since the range of comfort zone or thermo neutral zone of domestic chickens is narrow, they become easily susceptible to heat and cold environmental stress. We evaluated Brahma Rasayana (BR supplementation on concentrations of certain oxidative stress markers associated with heat stress. A total of 48 egg type male chickens of local strain were divided into six groups (n = 8 for the study. Three groups were fed with BR orally at the rate of 2 g/kg bw daily for 10 days prior to and during the period of experiment. Two of the four groups that were exposed to heat stress (HST i.e. to a temperature of 40 ± 1°C and relative humidity of 80 ± 5% in an environmental chamber for 4 h daily for 5 or 10 days, received BR orally. The other two groups remained as BR treated and untreated non-heat stressed (NHST controls. There was a significant (P < 0.05 increase in the activities of antioxidant enzymes in blood such as catalase (CAT and superoxide dismutase (SOD, as well as liver CAT, glutathione peroxidase (GPX and glutathione reductase (GR in NHST-BR treated and HST-BR treated (both 5 and 10 days chickens when compared with untreated controls. A great deal of significant (P < 0.05 variations were seen in serum and liver reduced glutathione (GSH concentration in NHST-BR treated and HST-BR treated (both 5 and 10 days chickens. Serum and liver lipid peroxidation levels were found to be significantly (P < 0.05 higher in HST-untreated (both 5 and 10 days chickens when compared with other groups. Thus BR supplementation during HST brings about enhanced action of enzymatic and non-enzymatic antioxidants, which nullified the undesired side effects of free radicals that are generated during HST.

  18. Responses of Landoltia punctata to cobalt and nickel: Removal, growth, photosynthesis, antioxidant system and starch metabolism.

    Science.gov (United States)

    Guo, Ling; Ding, Yanqiang; Xu, Yaliang; Li, Zhidan; Jin, Yanling; He, Kaize; Fang, Yang; Zhao, Hai

    2017-09-01

    Landoltia punctata has been considered as a potential bioenergy crop due to its high biomass and starch yields in different cultivations. Cobalt and nickel are known to induce starch accumulation in duckweed. We monitored the growth rate, net photosynthesis rate, total chlorophyll content, Rubisco activity, Co 2+ and Ni 2+ contents, activity of antioxidant enzymes, starch content and activity of related enzymes under various concentrations of cobalt and nickel. The results indicate that Co 2+ and Ni 2+ (≤0.5mgL -1 ) can facilitate growth in the beginning. Although the growth rate, net photosynthesis rate, chlorophyll content and Rubisco activity were significantly inhibited at higher concentrations (5mgL -1 ), the starch content increased sharply up to 53.3% dry weight (DW) in L. punctata. These results were attributed to the increase in adenosine diphosphate-glucose pyrophosphorylase (AGPase) and soluble starch synthase (SSS) activities and the decrease in α-amylase activity upon exposure to excess Co 2+ and Ni 2+ . In addition, a substantial increase in the antioxidant enzyme activities and high flavonoid contents in L. punctata may have largely resulted in the metal tolerance. Furthermore, the high Co 2+ and Ni 2+ contents (2012.9±18.8 and 1997.7±29.2mgkg -1 DW) in the tissue indicate that L. punctata is a hyperaccumulator. Thus, L. punctata can be considered as a potential candidate for the simultaneous bioremediation of Co 2+ - and Ni 2+ -polluted water and high-quality biomass production. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Indole-3-butyric acid mediates antioxidative defense systems to promote adventitious rooting in mung bean seedlings under cadmium and drought stresses.

    Science.gov (United States)

    Li, Shi-Weng; Zeng, Xiao-Ying; Leng, Yan; Feng, Lin; Kang, Xiao-Hu

    2018-06-08

    In vitro experiments were performed to determine whether auxin can mediate the formation of adventitious roots in response to heavy metal and drought stresses using a model rooting plant, mung bean [Vigna radiata (L.) Wilczek]. The treatments with CdCl 2 or mannitol alone significantly inhibited the formation and growth of adventitious roots in mung bean seedlings. In contrast, when CdCl 2 or mannitol was applied together with indole-3-butyric acid (IBA), IBA considerably cancelled the inhibition of adventitious rooting by stresses. Treatment with CdCl 2 or mannitol alone significantly increased the soluble protein and malondialdehyde (MDA) contents. CdCl 2 and mannitol stress each induced differentially significant changes in the activities of antioxidative enzyme and antioxidant levels during adventitious rooting. Notably, both CdCl 2 and mannitol stress strongly reduced the peroxidase (POD) and ascorbate peroxidase (APX) activities and glutathione (GSH) and phenols levels. Catalase and superoxide dismutase (SOD) activity were enhanced by CdCl 2 but reduced by mannitol. CdCl 2 increased the ascorbate acid (ASA) level, which was decreased by mannitol. Furthermore, when CdCl 2 or mannitol was applied together with IBA, IBA counteracted the CdCl 2 - or mannitol-induced increase or decrease in certain antioxidants, MDA, and antioxidative enzymes. These results suggest that Cd and mannitol stress inhibition of adventitious rooting is associated with the regulation of antioxidative enzymes and antioxidants in cells to defense the oxidative stress. Moreover, IBA alleviates the effects of Cd and mannitol stress on the rooting process partially through the regulation of antioxidative defense systems. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Depletion of microglia and inhibition of exosome synthesis halt tau propagation

    Science.gov (United States)

    Asai, Hirohide; Ikezu, Seiko; Tsunoda, Satoshi; Medalla, Maria; Luebke, Jennifer; Haydar, Tarik; Wolozin, Benjamin; Butovsky, Oleg; Kügler, Sebastian; Ikezu, Tsuneya

    2015-01-01

    Accumulation of pathological tau protein is a major hallmark of Alzheimer’s disease. Tau protein spreads from the entorhinal cortex to the hippocampal region early in the disease. Microglia, the primary phagocytes in the brain, are positively correlated with tau pathology, but their involvement in tau propagation is unknown. We developed an adeno-associated virus–based model exhibiting rapid tau propagation from the entorhinal cortex to the dentate gyrus in 4 weeks. We found that depleting microglia dramatically suppressed the propagation of tau and reduced excitability in the dentate gyrus in this mouse model. Moreover, we demonstrate that microglia spread tau via exosome secretion, and inhibiting exosome synthesis significantly reduced tau propagation in vitro and in vivo. These data suggest that microglia and exosomes contribute to the progression of tauopathy and that the exosome secretion pathway may be a therapeutic target. PMID:26436904

  1. Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis

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    Amanda Sierra

    2014-01-01

    Full Text Available Microglia cells are the major orchestrator of the brain inflammatory response. As such, they are traditionally studied in various contexts of trauma, injury, and disease, where they are well-known for regulating a wide range of physiological processes by their release of proinflammatory cytokines, reactive oxygen species, and trophic factors, among other crucial mediators. In the last few years, however, this classical view of microglia was challenged by a series of discoveries showing their active and positive contribution to normal brain functions. In light of these discoveries, surveillant microglia are now emerging as an important effector of cellular plasticity in the healthy brain, alongside astrocytes and other types of inflammatory cells. Here, we will review the roles of microglia in adult hippocampal neurogenesis and their regulation by inflammation during chronic stress, aging, and neurodegenerative diseases, with a particular emphasis on their underlying molecular mechanisms and their functional consequences for learning and memory.

  2. Alternative oxidase pathway optimizes photosynthesis during osmotic and temperature stress by regulating cellular ROS, malate valve and antioxidative systems

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    DINAKAR eCHALLABATHULA

    2016-02-01

    Full Text Available The present study reveals the importance of alternative oxidase (AOX pathway in optimizing photosynthesis under osmotic and temperature stress conditions in the mesophyll protoplasts of Pisum sativum. The responses of photosynthesis and respiration were monitored at saturating light intensity of 1000 µmoles m-2 s-1 at 25 oC under a range of sorbitol concentrations from 0.4 M to 1.0M to induce hyper-osmotic stress and by varying the temperature of the thermo-jacketed pre-incubation chamber from 25 oC to 10 oC to impose sub-optimal temperature stress. Compared to controls (0.4 M sorbitol and 25 OC, the mesophyll protoplasts showed remarkable decrease in NaHCO3-dependent O2 evolution (indicator of photosynthetic carbon assimilation, under both hyper-osmotic (1.0 M sorbitol and sub-optimal temperature stress conditions (10 OC, while the decrease in rates of respiratory O2 uptake were marginal. The capacity of AOX pathway increased significantly in parallel to increase in intracellular pyruvate and reactive oxygen species (ROS levels under both hyper-osmotic stress and sub-optimal temperature stress under the background of saturating light. The ratio of redox couple (Malate/OAA related to malate valve increased in contrast to the ratio of redox couple (GSH/GSSG related to antioxidative system during hyper-osmotic stress. Nevertheless, the ratio of GSH/GSSG decreased in the presence of sub-optimal temperature, while the ratio of Malate/OAA showed no visible changes. Also, the redox ratios of pyridine nucleotides increased under hyper-osmotic (NADH/NAD and sub-optimal temperature (NADPH/NADP stresses, respectively. However, upon restriction of AOX pathway by using salicylhydroxamic acid (SHAM, the observed changes in NaHCO3 dependent O2 evolution, cellular ROS, redox ratios of Malate/OAA, NAD(PH/NAD(P and GSH/GSSG were further aggravated under stress conditions with concomitant modulations in NADP-MDH and antioxidant enzymes. Taken together, the

  3. The effect of biologically active feed additives of humilid substances on the antioxidant system in liver mitochondria of gerbils

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    O. O. Dyomshina

    2017-04-01

    Full Text Available Mitochondria are organelles that are most sensitive to the action of stressors on any cell of the entire organism and exposure to chemicals which can cause its dysfunction and cell death in general. Especially sensitive to adverse conditions are liver mitochondria, where the processes of biotransformation of endogenous and exogenous metabolites are formed, not only in the liver, but also in other organs and tissues. Mitochondrial dysfunction can cause instant hepatic cytolysis and steatosis. Therefore, early detection of mitochondrial toxicity is important during preclinical studies of new pharmacological agents, as this will help avoid remote negative effects. The biologically active feed additive Humilid, a complex of humic acids known for their antidiarrheal, analgesic, immune-stimulating, and antimicrobial properties; shows a corrective effect on the activity of the lysosomal cathepsin; enhances the positive effect of hematopoiesis on hemoglobin and its quality indicators consisting of red blood cells; and activates the synthesis and accumulation of fibronectin expression that takes part in the formation of immunological protection of animals. The objective of our experiment was to determine the effect of complex biologically active feed additives based on humic substances on the biochemical indicators of the liver mitochondrial antioxidant system of Mongolian gerbils (Meriones unguiculatus Milne-Edwards, 1867. The experiment was conducted on mature (6 months Mongolian gerbils. The data obtained showing the influence of the biologically active feed additives Humilid, alone or in combination with ascorbate and Eco-impulse Animal, on the antioxidant defense system of liver mitochondria of gerbils are presented in this article. The proven antioxidant effect of humic substances in the mitochondrial fraction of the liver which inhibits the accumulation of oxidized products in the cells is shown, confirmed by the decrease in the number of TBA

  4. Treating Gulf War Illness with Novel Anti-Inflammatories: A Screening of Botantical Microglia Modulators

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0623 TITLE: Treating Gulf War Illness with Novel Anti-Inflammatories: A Screening of Botantical Microglia Modulators...Report 3. DATES COVERED 30 Sep 2015 - 29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Treating Gulf War Illness with Novel Anti...SUBJECT TERMS Gulf War Illness, botanical, anti-inflammatory, biomarker, microglia, improvement, treatment 16. SECURITY CLASSIFICATION OF: 17

  5. Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis (Dutch). An immunohistochemical study.

    Science.gov (United States)

    Maat-Schieman, M L; Rozemuller, A J; van Duinen, S G; Haan, J; Eikelenboom, P; Roos, R A

    1994-09-01

    In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) beta/A4 amyloid deposition is found in meningocortical blood vessels and in diffuse plaques in the cerebral cortex. Diffuse plaques putatively represent early stages in the formation of senile plaques. Microglia are intimately associated with congophilic plaques in Alzheimer's disease (AD), but microglial involvement in diffuse plaque formation is controversial. Therefore, we studied the relationship between microglia and diffuse plaques in the cerebral cortex of four patients with HCHWA-D using a panel of macrophage/microglia markers (mAbs LCA, LeuM5, LeuM3, LN3, KP1, OKIa, CLB54, Mac1, Ki-M6, AMC30 and the lectin RCA-1). Eight AD patients, one demented Down's syndrome (DS) patient and four non-demented controls were included for comparison. In controls and HCHWA-D patients ramified or "resting" microglia formed a reticular array in cortical gray and subcortical white matter. Microglial cells in or near HCHWA-D diffuse plaques retained their normal regular spacing and ramified morphology. In AD/DS gray matter more microglial cells were stained than in controls and HCHWA-D patients. Intensely immunoreactive microglia with enlarged cell bodies and short, thick processes clustered in congophilic plaques. In contrast to the resting microglia, these "activated microglia" strongly expressed class II major histocompatibility complex antigen, HLA-DR, and were AMC30-immunoreactive. These findings support the view that microglia play a role in the formation of congophilic plaques but do not initiate diffuse plaque formation. Another finding in this study is the presence of strong monocyte/macrophage marker immunoreactivity in the wall of cortical congophilic blood vessels in HCHWA-D.

  6. LEVEL OF ZINC AND ITS FRACTIONS AS REFLECTION OF A CONDITION OF ANTIOXIDANT SYSTEM AT THE CHRONIC OBSTRUCTIVE LUNG DISEASE

    Directory of Open Access Journals (Sweden)

    V. I. Shevcova

    2018-01-01

    Full Text Available Objective. To estimate a possibility of use of zinc and its fractions as the indicator reflecting a condition of antioxidant system at sick HOBL and persons from risk groups. Materials and methods. Patients with COPD, smokers and non-smoking healthy people have participated in a research. Everything participated in a research has carried out spirometry with definition of an indicator of FEV1 and the subsequent calculation of FEV1 % of due. Taking into account importance of the occupied role when forming COPD of an oxidative stress have been determined the level of activity of the main enzyme of antitoskidantny protection — superoxide dismutases; level of zinc and its fractions as main component of enzyme and also albumine as main tranporter of metabolic active zinc. The indicator “a share of the related fraction of zinc” for definition of changes in fractions of zinc is entered. Results of the study. It is defined that at the smoking patients with the minimum malfunction of external breath of change of indicators are similar to that at patients with COPD. Statistically significant differences in the level of the studied indicators at non-smoking patients are also revealed. With use of the correlation analysis of Spirmen reliable high correlation communications between FEV1 % from due and activity level superoxide dismutases and also between activity level superoxide dismutases and the general level of zinc and also zinc connected are defined that confirms a hypothesis of a possibility of use of level of zinc and its fractions as the indicator reflecting a condition of antioxidant system at the smoking persons at screening researches. 

  7. Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations.

    Science.gov (United States)

    Tronel, Claire; Largeau, Bérenger; Santiago Ribeiro, Maria Joao; Guilloteau, Denis; Dupont, Anne-Claire; Arlicot, Nicolas

    2017-04-11

    Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals' binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest. We overview alternative molecular targets, for which dedicated radiopharmaceuticals have been proposed, including receptors (purinergic receptors P2X7, cannabinoid receptors, α7 and α4β2 nicotinic acetylcholine receptors, adenosine 2A receptor, folate receptor β) and enzymes (cyclooxygenase, nitric oxide synthase, matrix metalloproteinase, β-glucuronidase, and enzymes of the kynurenine pathway), with a particular focus on their respective contribution for the understanding of microglial involvement in neurodegenerative diseases. We discuss opportunities for these potential molecular targets for PET imaging regarding their selectivity for microglia expression and polarization, in relation to the mechanisms by which microglia actively participate in both toxic and neuroprotective actions in brain diseases, and then take into account current clinicians' expectations.

  8. The effects of electromagnetic irradiation on activation of microglia and JAKs in rat hippocampus

    International Nuclear Information System (INIS)

    Chen Chunhai; Yang Xuesen; Hao Yutong; Zhang Guangbin; Yu Zhengping

    2008-01-01

    Objective: To determine the activation of microglia and the phosphorylation of Jaks, the upstream factors of JAK/STAT(janus activated kinase/signal transducers and activators of transcription) signaling pathway, after electromagnetic irradiation. Methods: Rats were irradiated by 90 mW/cm 2 EMF for 20 min. The phosphorylation of Jaks was determined by western blot at different time after electromagnetic irradiation. The activation of microglia was determined by immuno- chemistry. Results: GSA-IB4 was upregulated in microglia, which indicated microglia was activated after electromagnetic irradiation. The phosphorylation of Jak1, Jak2 and Jak3 in rat hippocampus was upregulated after electromagnetic irradiation. The phosphorylation of Jakl was upregulated after microwave exposure and peaked at 12 h. Jak2 peaked at 0 h after electro-magnetic irradiation and sustained in a high level. Jak3 was slightly affected by electromagnetic irradiation. All the three members of JAKs return to normal at 72 h after electromagnetic irradiation. Conclusion: Microglia cells was activated after electromagnetic irradiation. The phosphorylation of Jaks was upregulated by electromagnetic irradiation. It suggested that JAK/ STAT singnaling pathway was activated after electromagnetic irradiation, which indicated that JAK/STAT signaling pathway may participate in brain microglia activation induced by electromagnetic irradiation. (authors)

  9. Degradation of Alzheimer's amyloid fibrils by microglia requires delivery of ClC-7 to lysosomes

    Science.gov (United States)

    Majumdar, Amitabha; Capetillo-Zarate, Estibaliz; Cruz, Dana; Gouras, Gunnar K.; Maxfield, Frederick R.

    2011-01-01

    Incomplete lysosomal acidification in microglia inhibits the degradation of fibrillar forms of Alzheimer's amyloid β peptide (fAβ). Here we show that in primary microglia a chloride transporter, ClC-7, is not delivered efficiently to lysosomes, causing incomplete lysosomal acidification. ClC-7 protein is synthesized by microglia but it is mistargeted and appears to be degraded by an endoplasmic reticulum–associated degradation pathway. Activation of microglia with macrophage colony-stimulating factor induces trafficking of ClC-7 to lysosomes, leading to lysosomal acidification and increased fAβ degradation. ClC-7 associates with another protein, Ostm1, which plays an important role in its correct lysosomal targeting. Expression of both ClC-7 and Ostm1 is increased in activated microglia, which can account for the increased delivery of ClC-7 to lysosomes. Our findings suggest a novel mechanism of lysosomal pH regulation in activated microglia that is required for fAβ degradation. PMID:21441306

  10. Tubulin cofactor B regulates microtubule densities during microglia transition to the reactive states

    International Nuclear Information System (INIS)

    Fanarraga, M.L.; Villegas, J.C.; Carranza, G.; Castano, R.; Zabala, J.C.

    2009-01-01

    Microglia are highly dynamic cells of the CNS that continuously survey the welfare of the neural parenchyma and play key roles modulating neurogenesis and neuronal cell death. In response to injury or pathogen invasion parenchymal microglia transforms into a more active cell that proliferates, migrates and behaves as a macrophage. The acquisition of these extra skills implicates enormous modifications of the microtubule and actin cytoskeletons. Here we show that tubulin cofactor B (TBCB), which has been found to contribute to various aspects of microtubule dynamics in vivo, is also implicated in microglial cytoskeletal changes. We find that TBCB is upregulated in post-lesion reactive parenchymal microglia/macrophages, in interferon treated BV-2 microglial cells, and in neonate amoeboid microglia where the microtubule densities are remarkably low. Our data demonstrate that upon TBCB downregulation both, after microglia differentiation to the ramified phenotype in vivo and in vitro, or after TBCB gene silencing, microtubule densities are restored in these cells. Taken together these observations support the view that TBCB functions as a microtubule density regulator in microglia during activation, and provide an insight into the understanding of the complex mechanisms controlling microtubule reorganization during microglial transition between the amoeboid, ramified, and reactive phenotypes

  11. Spinal microglia: A potential target in the treatment of chronic visceral pain

    Directory of Open Access Journals (Sweden)

    Ching-Liang Lu

    2014-01-01

    Full Text Available Chronic visceral pain is the predominant symptom of functional gastrointestinal disorders and chronic pancreatitis. Such pain can impair the patients' quality of life, and can also serve as one of the principal reasons for these patients to seek medical help. Nevertheless, the underlying mechanisms of chronic visceral pain have remained unclear, and much of what we know about visceral pain has been derived from studies of somatic nociception. Current treatment of chronic visceral pain has continued to be unsatisfactory, because of unclear pathophysiology. However, recent progress in pain research has identified the important role of spinal microglia in the development of somatic nociception. For visceral pain, several animal studies have demonstrated that spinal cord microglia is activated during the development of visceral hyperalgesia, which can be induced by neonatal colorectal irritation, psychological stress, and trinitrobenzene sulfonic acid-induced pancreatitis. This visceral hyperalgesia is also associated with elevated phosphorylation of p38 mitogen-activated protein kinase. Minocycline (a microglia inhibitor reversed the hyperalgesia in rat models of chronic visceral pain, whereas fractalkine (FKN, a microglia activator reproduced the visceral nociception in naïve rats. These preliminary results support the pronociceptive role of spinal microglia in mediating visceral hyperalgesia. Consequently, spinal microglia may serve as a promising target for controlling the chronic visceral pain.

  12. From development to dysfunction: microglia and the complement cascade in CNS homeostasis.

    Science.gov (United States)

    Zabel, Matthew K; Kirsch, Wolff M

    2013-06-01

    Of the many mysteries that surround the brain, few surpass the awe-inspiring complexity of its development. The intricate wiring of the brain at both the system and molecular level is both spatially and temporally regulated in perfect synchrony. How such a delicate, yet elegant, system arises from an embryo's most basic cells remains at the forefront of neuroscientific research. At the cellular level, the competitive dance between synapses struggling to gain dominance seems to be refereed by both neurons themselves and microglia, the innate immune cells of the nervous system. Additionally, the unexpected complement cascade, a major effecter arm of the innate immune system, is almost certainly involved in synaptic remodeling by tagging destined neurons and synapses for destruction. As suddenly as they appear, the mechanisms of neurogenesis recede entering into adulthood. However, with age and insult, these mechanisms boisterously return, resulting in neurodegeneration. This review describes some of the mechanisms involved in synaptogenesis and wiring of the brain from the point of view of the innate immune system and then covers how similar molecular processes return with age and disease, specifically in the context of Alzheimer's disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer.

    Science.gov (United States)

    Zuikov, S A; Borzenko, B G; Shatova, O P; Bakurova, E M; Polunin, G E

    2014-06-01

    To examine the relationship between metabolic features of purine nucleotides and antioxidant system depending on the age of patients with colorectal cancer. The activity of adenosine deaminase, xanthine oxidase, glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase, the NOx concentration and the oxidative modification of proteins were determined spectrophotometricaly in 50 apparently healthy people and 26 patients with colorectal cancer stage -III---IV, aged 40 to 79 years. Increase of pro-oxidant system of erythrocytes with the age against decrease in level of antioxidant protection in both healthy individuals and colorectal cancer patients was determined. A significant increase of pro-ducts of oxidative proteins modification in erythrocytes with ageing was shown. Statistically significant correlation between enzymatic and non enzymatic markers pro-oxidant system and the activity of antioxidant defense enzymes in erythrocytes of patient with colorectal cancer was determined. Obtained results have demonstrated the imbalance in the antioxidant system of erythrocytes in colorectal cancer patients that improve the survival of cancer cells that is more distinctly manifested in ageing.

  14. Modulation of Antioxidant Defense System Is Associated with Combined Drought and Heat Stress Tolerance in Citrus

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    Sara I. Zandalinas

    2017-06-01

    Full Text Available Drought and high temperatures are two major abiotic stress factors that often occur simultaneously in nature, affecting negatively crop performance and yield. Moreover, these environmental challenges induce oxidative stress in plants through the production of reactive oxygen species (ROS. Carrizo citrange and Cleopatra mandarin are two citrus genotypes with contrasting ability to cope with the combination of drought and heat stress. In this work, a direct relationship between an increased antioxidant activity and stress tolerance is reported. According to our results, the ability of Carrizo plants to efficiently coordinate superoxide dismutase (SOD, ascorbate peroxidase (APX, catalase (CAT, and glutathione reductase (GR activities involved in ROS detoxification along with the maintenance of a favorable GSH/GSSG ratio could be related to their relative tolerance to this stress combination. On the other hand, the increment of SOD activity and the inefficient GR activation along with the lack of CAT and APX activities in Cleopatra plants in response to the combination of drought and heat stress, could contribute to an increased oxidative stress and the higher sensibility of this citrus genotype to this stress combination.

  15. Modulation of Antioxidant Defense System Is Associated with Combined Drought and Heat Stress Tolerance in Citrus.

    Science.gov (United States)

    Zandalinas, Sara I; Balfagón, Damián; Arbona, Vicent; Gómez-Cadenas, Aurelio

    2017-01-01

    Drought and high temperatures are two major abiotic stress factors that often occur simultaneously in nature, affecting negatively crop performance and yield. Moreover, these environmental challenges induce oxidative stress in plants through the production of reactive oxygen species (ROS). Carrizo citrange and Cleopatra mandarin are two citrus genotypes with contrasting ability to cope with the combination of drought and heat stress. In this work, a direct relationship between an increased antioxidant activity and stress tolerance is reported. According to our results, the ability of Carrizo plants to efficiently coordinate superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and glutathione reductase (GR) activities involved in ROS detoxification along with the maintenance of a favorable GSH/GSSG ratio could be related to their relative tolerance to this stress combination. On the other hand, the increment of SOD activity and the inefficient GR activation along with the lack of CAT and APX activities in Cleopatra plants in response to the combination of drought and heat stress, could contribute to an increased oxidative stress and the higher sensibility of this citrus genotype to this stress combination.

  16. Effects of 4-nonylphenol on oxidant/antioxidant balance system inducing hepatic steatosis in male rat

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    Ansoumane Kourouma

    2015-01-01

    Full Text Available An emerging literature suggests that early life exposure to 4-nonylphenol (4-NP, a widespread endocrine disrupting chemical, may increase the risk of metabolic syndrome. In this study, we investigated the hypothesis that intraperitoneal administration of 4-NP induces hepatic steatosis in rat. 24 male Sprague-Dawley rats were administered with 4-NP (0, 2, 10 and 50 mg/kg b.wt in corn oil for 30 days. Liver histology, biochemical analysis and gene expression profiling were examined. After treatment, abnormal liver morphology and function were observed in the 4-NP-treated rat, and significant changes in gene expression an indicator of hepatic steatosis and apoptosis were observed compared with controls. Up-regulated genes involved in apoptosis, hepatotoxity and oxidative stress, increased ROS and decrease of antioxidant enzyme were observed in the 4-NP exposed rat. Extensive fatty accumulation in liver section and elevated serum GOT, GPT, LDH and γ-GT were also observed. Incidence and severity of liver steatosis was scored and taken into consideration (steatosis, ballooning and lobular inflammation. Hepatocytes apoptosis could promote NAFLD progression; Fas/FasL, TNF-α and Caspase-9 mRNA activation were important contributing factors to hepatic steatosis. These findings provide the first evidence that 4-NP affects the gene expression related to liver hepatotoxicity, which is correlated with hepatic steatosis.

  17. Impact of Static Magnetic Field on the Antioxidant Defence System of Mice Fibroblasts

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    Marek Glinka

    2018-01-01

    Full Text Available Results of research assessing the biological impact of static magnetic fields are controversial. So far, they have not provided a clear answer to their influence on cell functioning. Since the use of permanent magnets both in everyday life and in industry becomes more and more widespread, the investigations are continued in order to explain these controversies and to evaluate positive applications. The goal of current work was to assess the impact of static magnetic field of different intensities on redox homeostasis in cultures of fibroblasts. The use of permanent magnets allowed avoiding the thermal effects which are present in electromagnets. During the research we used 6 chambers, designed exclusively by us, with different values of field flux density (varying from 0.1 to 0.7 T. We have noted the decrease in the activity of superoxide dismutase (SOD and glutathione peroxidase (GPx. The static magnetic fields did not modify the energy state of fibroblasts— adenosine triphosphate (ATP concentration was stable, as well as the generation of malondialdehyde (MDA—which is a marker of oxidative stress. Results of research suggest that static magnetic fields generated by permanent magnets do not cause oxidative stress in investigated fibroblasts and that they may show slight antioxidizing activity.

  18. Alterations in antioxidant system, mitochondrial biogenesis and autophagy in preeclamptic myometrium

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    Polina A. Vishnyakova

    2017-12-01

    Full Text Available Preeclampsia is a pregnancy complication which causes significant maternal and fetal morbidity and mortality worldwide. Although intensive research has been performed in the last 40 years, the pathology of preeclampsia is still poorly understood. The present work is a comparative study of the myometrium of women with normal pregnancy, and those with late- and early-onset preeclampsia (n = 10 for each group. We observed significant changes in the levels of antioxidant enzymes, markers of mitochondrial biogenesis and autophagy proteins in preeclamptic myometrium. Levels of superoxide dismutase 1 and catalase were lower in both preeclamptic groups than the control group. In late-onset preeclampsia, expression levels of essential mitochondria-related proteins VDAC1, TFAM, hexokinase 1, PGC-1α and PGC-1β, and autophagy marker LC3A, were significantly elevated. In the myometrium of the early-onset preeclampsia group OPA1 and Bcl-2 were up-regulated compared to those of the control (p < 0.05. These findings suggest that crucial molecular changes in the maternal myometrium occur with the development of preeclampsia.

  19. Measurement of Antioxidant Effects on the Auto-oxidation Kinetics of Methyl Oleate – Methyl Laurate Blend as a Surrogate Biodiesel System

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    Tjokorde Walmiki Samadhi

    2017-05-01

    Full Text Available This research investigates the feasibility of methyl oleate-methyl laurate blend as a surrogate biodiesel system which represents jatropha-coconut oil biodiesel, a potentially suitable formulation for tropical climate, to quantify the efficacy of antioxidant additives in terms of their kinetic parameters. This blend was tested by the Rancimat EN14112 standard method. The Rancimat tests results were used to determine the primary oxidation induction period (OIP and first-order rate constants and activation energies. Addition of BHT and EcotiveTM antioxidants reduces the rate constants (k, h-1 between 15 to 90% in the 50-200 ppm dose range, with EcotiveTM producing significantly lower k values. Higher dose reduces the rate constant, while oleate/laurate ratio produces no significant impact. Antioxidants increase the oxidation activation energy (Ea, kJ/mol by 180 to almost 400% relative to the non-antioxidant value of 27.0 kJ/mol. EcotiveTM exhibits lower Ea, implying that its higher efficacy stems from a better steric hindrance as apparent from its higher pre-exponential factors. The ability to quantify oxidation kinetic parameters is indicative of the usefulness of methyl oleate-laurate pure FAME blend as a biodiesel surrogate offering better measurement accuracy due to the absence of pre-existing antioxidants in the test samples. Copyright © 2017 BCREC GROUP. All rights reserved Received: 6th July 2016; Revised: 7th December 2016; Accepted: 30th January 2017 How to Cite: Samadhi, T.W., Hirotsu, T., Goto, S. (2017. Measurement of Antioxidant Effects on the Auto-oxidation Kinetics of Methyl Oleate-Methyl Laurate Blend as a Surrogate Biodiesel System. Bulletin of Chemical Reaction Engineering & Catalysis, 12 (2: 157-166 (doi:10.9767/bcrec.12.2.861.157-166 Permalink/DOI: http://dx.doi.org/10.9767/bcrec.12.2.861.157-166

  20. Adverse effects of methylmercury (MeHg) on life parameters, antioxidant systems, and MAPK signaling pathways in the rotifer Brachionus koreanus and the copepod Paracyclopina nana.

    Science.gov (United States)

    Lee, Young Hwan; Kim, Duck-Hyun; Kang, Hye-Min; Wang, Minghua; Jeong, Chang-Bum; Lee, Jae-Seong

    2017-09-01

    To evaluate the adverse effects of MeHg on the rotifer Brachionus koreanus and the copepod Paracyclopina nana, we assessed the effects of MeHg toxicity on life parameters (e.g. growth retardation and fecundity), antioxidant systems, and mitogen-activated protein kinase (MAPK) signaling pathways at various concentrations (1ng/L, 10ng/L, 100ng/L, 500ng/L, and 1000ng/L). MeHg exposure resulted in the growth retardation with the increased ROS levels but decreased glutathione (GSH) levels in a dose-dependent manner in both B. koreanus and P. nana. Antioxidant enzymatic activities (e.g. glutathione S-transferase [GST], glutathione reductase [GR], and glutathione peroxidase [GPx]) in B. koreanus showed more positive responses compared the control but in P. nana, those antioxidant enzymatic activities showed subtle changes due to different no observed effect concentration (NOEC) values among the two species. Expression of antioxidant genes (e.g. superoxide dismutase [SOD], GSTs, glutathione peroxidase [GPx], and catalase [CAT]) also demonstrated similar effects as shown in antioxidant enzymatic activities. In B. koreanus, the level of p-ERK was decreased in the presence of 1000ng/L MeHg, while the levels of p-ERK and p-p38 in P. nana were reduced in the presence of 10ng/L MeHg. However, p-JNK levels were not altered by MeHg in B. koreanus and P. nana, compared to the corresponding controls. In summary, life parameters (e.g. reduced fecundity and survival rate) were closely associated with effects on the antioxidant system in response to MeHg. These observations provide a better understanding on the adverse effects of MeHg on in vivo life parameters and molecular defense mechanisms in B. koreanus and P. nana. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Optimization of Microwave-Assisted Extraction of Curcumin From Curcuma longa L. (Turmeric and Evaluation of Antioxidant Activity in Multi-Test Systems

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    Mustafa Bener

    2016-03-01

    Full Text Available Turmeric ( Curcuma longa L. is a medicinal plant, and its biological activities mainly arise from the main constituent, known as diferuloylmethane or curcumin. In the present paper, microwave-assisted extraction (MAE was investigated for the recovery of curcumin from turmeric in comparison to conventional heat-assisted extraction (CHAE technique. Various experimental conditions, such as solvent concentration (0-100%, v/v, MAE temperature (30-130 oC and MAE time (0-20 min were investigated to optimize the extraction of curcumin from turmeric. The identification and quantification of curcumin in extracts were performed by HPLC-DAD system. Antioxidant potential and radical scavenging abilities of microwave-assisted extract and conventional heat-assisted extract of turmeric (MAET and CHAET were evaluated using different systems including total phenolic content (TPC, total antioxidant capacity (TAC, and radical scavenging activities. MAET and CHAET showed high antioxidant activity in all test systems, but the antioxidant properties of MAET were stronger than those of CHAET.

  2. Effects of antimony on redox activities and antioxidant defence systems in sunflower (Helianthus annuus L. plants.

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    Alfonso Ortega

    Full Text Available The alterations induced by the toxicity of antimony (Sb in the roots and leaves of sunflower plants were determined. The plants were grown hydroponically with different concentrations of Sb, a heavy metal which reduces biomass production and growth. There was preferential accumulation of Sb in the tissues of the roots, with the concentrations in the leaves being much lower. The accumulation of other mineral elements was also altered, especially that of Fe and Zn. Chlorophyll content declined, as also did the photosynthetic efficiency, but the carotenoid content remained unaltered. The total content of phenolics, flavonoids, and phenylpropanoid glycosides rose, evidence of their participation in the defence response. Increases were observed in the amount of superoxide anion in both roots and leaves, and in lipid peroxidation levels, especially with the highest Sb concentration of 1.0 mM. The induced oxidative stress leads to a strong increase in the SOD, POX and APX antioxidant activities, while the GR activity was only increased in the leaves and at the 1.0 mM Sb concentration. In contrast, the DHAR activity increased considerably in both organs. The GSNOR activity increased only in roots, and the total RSNOs increased. The total amount of AsA + DHA increased in roots and remained unaltered in leaves, whereas that of GSH + GSSG decreased considerably in all cases. As a whole, these results are evidence for the development of a strong oxidative stress induced by Sb, with there being a clear imbalance in the content of the compounds that constitute the AsA/GSH cycle. 0.5 mM Sb enhances GST expression, especially in leaves. This, together with the increase that was observed in the amount of GSH, may play an important part in detoxification. This oxidative stress affects both the phenolic and the ROS/RNS metabolic processes, which seems to implicate their involvement in the plant's defence and response to the stress.

  3. Exogenous 5-Aminolevulenic Acid Promotes Antioxidative Defence System, Photosynthesis and Growth in Soybean against Cold Stress

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    Elahe MANAFI

    2015-12-01

    Full Text Available In the present study, the possibility of enhancing cold stress tolerance of young soybean plants (Glycine max [L.] Merr by exogenous application of 5-aminolevulinic acid (ALA was investigated. ALA was applied at various concentrations (0, 0.3, 0.6 and 0.9 mM by seed priming and foliar application method. After ALA treatment, the plants were subjected to cold stress at 10 ± 0.5 °C for 72 h. Cold stress significantly decreased plant growth, relative water content, chlorophyll, photosynthesis and stomatal conductivity, while it increased electrolyte leakage and proline accumulation. ALA at low concentrations (0.3 mM protected plants against cold stress, enhancing plant height, shoot fresh and dry weight, chlorophyll content, photosynthesis, stomatal conductivity as well as relative water content. Increase of electrolyte leakage was also prevented by 0.6 mM ALA. ALA also enhanced superoxide dismutase and catalase activities at 0.6 mM concentration especially under cold stress conditions. Proline increased with increasing in ALA concentration under both temperature conditions. In most cases, application of ALA by spraying method was better than seed priming method. Results showed that ALA, which is considered as an endogenous plant growth regulator, can be used effectively to protect soybean plants from the damaging effects of cold stress, by enhancing the activity of antioxidative enzymes, protecting cell membrane against reactive oxygen species and finally by promoting chlorophyll synthesis, leading to more intense photosynthesis and more carbon fixation, without any adverse effect on the plant growth.

  4. Microglia and neurons in the hippocampus of migratory sandpipers

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    C.G. Diniz

    2016-01-01

    Full Text Available The semipalmated sandpiper Calidris pusilla and the spotted sandpiper Actitis macularia are long- and short-distance migrants, respectively. C. pusilla breeds in the sub-arctic and mid-arctic tundra of Canada and Alaska and winters on the north and east coasts of South America. A. macularia breeds in a broad distribution across most of North America from the treeline to the southern United States. It winters in the southern United States, and Central and South America. The autumn migration route of C. pusilla includes a non-stop flight over the Atlantic Ocean, whereas autumn route of A. macularia is largely over land. Because of this difference in their migratory paths and the visuo-spatial recognition tasks involved, we hypothesized that hippocampal volume and neuronal and glial numbers would differ between these two species. A. macularia did not differ from C. pusilla in the total number of hippocampal neurons, but the species had a larger hippocampal formation and more hippocampal microglia. It remains to be investigated whether these differences indicate interspecies differences or neural specializations associated with different strategies of orientation and navigation.

  5. PLD$ is involved in phagocytosis of microglia: expression and localization changes of PLD4 are correlated with activation state of microglia.

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    Yoshinori Otani

    Full Text Available Phospholipase D4 (PLD4 is a recently identified protein that is mainly expressed in the ionized calcium binding adapter molecule 1 (Iba1-positive microglia in the early postnatal mouse cerebellar white matter. Unlike PLD1 and PLD2, PLD4 exhibits no enzymatic activity for conversion of phosphatidylcholine into choline and phosphatidic acid, and its function is completely unknown. In the present study, we examined the distribution of PLD4 in mouse cerebellar white matter during development and under pathological conditions. Immunohistochemical analysis revealed that PLD4 expression was associated with microglial activation under such two different circumstances. A primary cultured microglia and microglial cell line (MG6 showed that PLD4 was mainly present in the nucleus, except the nucleolus, and expression of PLD4 was upregulated by lipopolysaccharide (LPS stimulation. In the analysis of phagocytosis of LPS-stimulated microglia, PLD4 was co-localized with phagosomes that contained BioParticles. Inhibition of PLD4 expression using PLD4 specific small interfering RNA (siRNA in MG6 cells significantly reduced the ratio of phagocytotic cell numbers. These results suggest that the increased PLD4 in the activation process is involved in phagocytosis of activated microglia in the developmental stages and pathological conditions of white matter.

  6. Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood

    NARCIS (Netherlands)

    Schaafsma, Wandert; Basterra, Laura Bozal; Jacobs, Sabrina; Brouwer, Nieske; Meerlo, Peter; Schaafsma, Anne; Boddeke, Erik W. G. M.; Eggen, Bart J. L.

    2017-01-01

    Maternal inflammation during pregnancy can have detrimental effects on embryonic development that persist during adulthood. However, the underlying mechanisms and insights in the responsible cell types are still largely unknown. Here we report the effect of maternal inflammation on fetal microglia,

  7. Cumulative abiotic stresses and their effect on the antioxidant defense system in two species of wheat, Triticum durum Desf and Triticum aestivum L.

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    Ibrahim M.M.

    2013-01-01

    Full Text Available The combined effects of heat and UV-B on the antioxidant system and photosynthetic pigments were investigated in the leaves of T. durum Desf. and Triticum aestivum L. The photosynthetic pigment content, in vitro evaluation of the antioxidant system activities including DPPH radical scavenging activity, and super oxide anion radical scavenging activity were determined. In addition, the antioxidant enzyme activities, such as superoxide dismutase (SOD and guaiacol peroxidase (GPX, were determined. Heat and UV-B irradiation alone caused a significant decrease in the photosynthetic pigment content, radical scavenging activity and super oxide radical scavenging activity in the two studied plants. The antioxidant enzymes SOD and GPX were stimulated in response to UV and/or heat stresses. The elevation of enzyme activities was higher under heat than under UV-B, especially in T. aestivum. According to our findings, it can be concluded that combined heat and UV-B provided cross-tolerance; otherwise, single stress was found to aggravate the responses.

  8. Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model.

    Science.gov (United States)

    Aryanpour, Roya; Pasbakhsh, Parichehr; Zibara, Kazem; Namjoo, Zeinab; Beigi Boroujeni, Fatemeh; Shahbeigi, Saeed; Kashani, Iraj Ragerdi; Beyer, Cordian; Zendehdel, Adib

    2017-10-01

    Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ+PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice. In addition, CPZ+PRO caused a significant reduction in the mRNA expression levels of M1-markers (iNOS, CD86, MHC-II and TNF-α) in the corpus callosum region, whereas the expression of M2-markers (Trem-2, CD206, Arg-1 and TGF-β) was significantly increased, in comparison to CPZ mice. Moreover, CPZ+PRO resulted in a significant decrease in the number of iNOS + and Iba-1 + /iNOS + cells (M1), whereas TREM-2 + and Iba-1 + /TREM-2 + cells (M2) significantly increased, in comparison to CPZ group. Furthermore, CPZ+PRO caused a significant decrease in mRNA and protein expression levels of NLRP3 and IL-18 (~2-fold), in comparison to the CPZ group. Finally, CPZ+PRO therapy was accompanied with reduced levels of demyelination, compared to CPZ, as confirmed by immunofluorescence to myelin basic protein (MBP) and Luxol Fast Blue (LFB) staining, as well as transmission electron microscopy (TEM) analysis. In summary, we reported for the first time that PRO therapy causes polarization of M2 microglia, attenuation of M1 phenotype, and suppression of NLRP3 inflammasome in a CPZ-induced demyelination model of MS. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Extended magnetic resonance imaging studies on the effect of classically activated microglia transplantation on white matter regeneration following spinal cord focal injury in adult rats

    Science.gov (United States)

    Marcol, Wiesław; Ślusarczyk, Wojciech; Larysz-Brysz, Magdalena; Łabuzek, Krzysztof; Kapustka, Bartosz; Staszkiewicz, Rafał; Rosicka, Paulina; Kalita, Katarzyna; Węglarz, Władysław; Lewin-Kowalik, Joanna

    2017-01-01

    Spinal cord injuries are still a serious problem for regenerative medicine. Previous research has demonstrated that activated microglia accumulate in spinal lesions, influencing the injured tissues in various ways. Therefore, transplantation of activated microglia may have a beneficial role in the regeneration of the nervous system. The present study examined the influence of transplanted activated microglial cells in adult rats with injured spinal cords. Rats were randomly divided into an experimental (M) and control (C) group, and were subjected to non-laminectomy focal injury of spinal cord white matter by means of a high-pressured air stream. In group M, activated cultured microglial cells were injected twice into the site of injury. Functional outcome and morphological features of regeneration were analyzed during a 12-week follow-up. The lesions were characterized by means of magnetic resonance imaging (MRI). Neurons in the brain stem and motor cortex were labeled with FluoroGold (FG). A total of 12 weeks after surgery, spinal cords and brains were collected and subjected to histopathological and immunohistochemical examinations. Lesion sizes in the spinal cord were measured and the number of FG-positive neurons was counted. Rats in group M demonstrated significant improvement of locomotor performance when compared with group C (PMRI analysis demonstrated moderate improvement in water diffusion along the spinal cord in the group M following microglia treatment, as compared with group C. The water diffusion perpendicular to the spinal cord in group M was closer to the reference values for a healthy spinal cord than it was in group C. The sizes of lesions were also significantly smaller in group M than in the group C (P<0.05). The number of brain stem and motor cortex FG-positive neurons in group M was significantly higher than in group C. The present study demonstrated that delivery of activated microglia directly into the injured spinal cord gives some

  10. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    International Nuclear Information System (INIS)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L.

    2016-01-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases

  11. Prostaglandin E2 released from activated microglia enhances astrocyte proliferation in vitro

    International Nuclear Information System (INIS)

    Zhang Dan; Hu Xiaoming; Qian Li; Wilson, Belinda; Lee, Christopher; Flood, Patrick; Langenbach, Robert; Hong, J.-S.

    2009-01-01

    Microglial activation has been implicated in many astrogliosis-related pathological conditions including astroglioma; however, the detailed mechanism is not clear. In this study, we used primary enriched microglia and astrocyte cultures to determine the role of microglial prostaglandin E 2 (PGE 2 ) in the proliferation of astrocytes. The proliferation of astrocytes was measured by BrdU incorporation. The level of PGE 2 was measured by ELISA method. Pharmacological inhibition or genetic ablation of COX-2 in microglia were also applied in this study. We found that proliferation of astrocytes increased following lipopolysaccharide (LPS) treatment in the presence of microglia. Furthermore, increased proliferation of astrocytes was observed in the presence of conditioned media from LPS-treated microglia. The potential involvement of microglial PGE 2 in enhanced astrocyte proliferation was suggested by the findings that PGE 2 production and COX-2 expression in microglia were increased by LPS treatment. In addition, activated microglia-induced increases in astrocyte proliferation were blocked by the PGE 2 antagonist AH6809, COX-2 selective inhibitor DuP-697 or by genetic knockout of microglial COX-2. These findings were further supported by the finding that addition of PGE 2 to the media significantly induced astrocyte proliferation. These results indicate that microglial PGE 2 plays an important role in astrocyte proliferation, identifying PGE 2 as a key neuroinflammatory molecule that triggers the pathological response related to uncontrollable astrocyte proliferation. These findings are important in elucidating the role of activated microglia and PGE 2 in astrocyte proliferation and in suggesting a potential avenue in the use of anti-inflammatory agents for the therapy of astroglioma.

  12. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

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    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L. [Department of Neurology, Shenzhen Hospital, Peking University, Shenzhen (China)

    2016-08-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

  13. α-Iso-cubebene exerts neuroprotective effects in amyloid beta stimulated microglia activation.

    Science.gov (United States)

    Park, Sun Young; Park, Se Jin; Park, Nan Jeong; Joo, Woo Hong; Lee, Sang-Joon; Choi, Young-Whan

    2013-10-25

    Schisandra chinensis is commonly used for food and as a traditional remedy for the treatment of neuronal disorders. However, it is unclear which component of S. chinensis is responsible for its neuropharmacological effects. To answer this question, we isolated α-iso-cubebene, a dibenzocyclooctadiene lignin, from S. chinensis and determined if it has any anti-neuroinflammatory and neuroprotective properties against amyloid β-induced neuroinflammation in microglia. Microglia that are stimulated by amyloid β increased their production of pro-inflammatory cytokines and chemokines, prostaglandin E2 (PGE2), nitric oxide (NO) and reactive oxygen species (ROS) and the enzymatic activity of matrix metalloproteinase 9 (MMP-9). We found this was all inhibited by α-iso-cubebene. Consistent with these results, α-iso-cubebene inhibited the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and MMP-9 in amyloid β-stimulated microglia. Subsequent mechanistic studies revealed that α-iso-cubebene inhibited the phosphorylation and degradation of IκB-α, the phosphorylation and transactivity of NF-κB, and the phosphorylation of MAPK in amyloid β-stimulated microglia. These results suggest that α-iso-cubebene impairs the amyloid β-induced neuroinflammatory response of microglia by inhibiting the NF-κB and MAPK signaling pathways. Importantly, α-iso-cubebene can provide critical neuroprotection for primary cortical neurons against amyloid β-stimulated microglia-mediated neurotoxicity. To the best of our knowledge, this is the first report showing that α-iso-cubebene can provide neuroprotection against, and influence neuroinflammation triggered by, amyloid β activation of microglia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Lycopene activates antioxidant enzymes and nuclear transcription factor systems in heat-stressed broilers.

    Science.gov (United States)

    Sahin, K; Orhan, C; Tuzcu, M; Sahin, N; Hayirli, A; Bilgili, S; Kucuk, O

    2016-05-01

    This study was conducted to evaluate the effects of dietary lycopene supplementation on growth performance, antioxidant status, and muscle nuclear transcription factor [Kelch like-ECH-associated protein 1 (Keap1) and (erythroid-derived 2)-like 2 (Nrf2)] expressions in broiler chickens exposed to heat stress (HS). A total of 180 one-day-old male broiler chicks (Ross 308) were assigned randomly to one of 2×3 factorially arranged treatments: two housing temperatures (22°C for 24 h/d; thermoneutral, TN or 34°C for 8 h/d HS) and three dietary lycopene levels (0, 200, or 400 mg/kg). Each treatment consisted of three replicates of 10 birds. Birds were reared to 42 d of age. Heat stress caused reductions in feed intake and weight gain by 12.2 and 20.7% and increased feed efficiency by 10.8% (Plycopene level improved performance in both environments. Birds reared under the HS environment had lower serum and muscle lycopene concentration (0.34 vs. 0.50 μg/mL and 2.80 vs. 2.13 μg/g), activities of superoxide dismutase (151 vs. 126 U/mL and 131 vs. 155 U/mg protein), glutathione peroxidase (184 vs. 154 U/mL and 1.39 vs. 1.74 U/mg protein), and higher malondialdehyde (MDA) concentration (0.53 vs. 0.83 μg/mL and 0.78 vs. 0.45 μg/ mg protein) than birds reared under the TN environment. Changes in levels of lycopene and MDA and activities of enzymes in serum and muscle varied by the environmental temperature as dietary lycopene level increased. Moreover, increasing dietary lycopene level suppressed muscle Keap1 expression and enhanced muscle Nrf2 expression, which had increased by 150% and decreased by 40%, respectively in response to HS. In conclusion, lycopene supplementation alleviates adverse effects of HS on performance through modulating expressions of stress-related nuclear transcription factors. © 2016 Poultry Science Association Inc.

  15. Activation of TRPV1 by capsaicin induces functional Kinin B1 receptor in rat spinal cord microglia

    Directory of Open Access Journals (Sweden)

    Talbot Sébastien

    2012-01-01

    Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines and oxydative stress, which are enhanced by transient receptor potential vanilloid subtype 1 (TRPV1 activation. To examine the link between TRPV1 and B1R in inflammatory pain, this study aimed to determine the ability of TRPV1 to regulate microglial B1R expression in the spinal cord dorsal horn, and the underlying mechanism. Methods B1R expression (mRNA, protein and binding sites was measured in cervical, thoracic and lumbar spinal cord in response to TRPV1 activation by systemic capsaicin (1-50 mg/kg, s.c in rats pre-treated with TRPV1 antagonists (capsazepine or SB-366791, the antioxidant N-acetyl-L-cysteine (NAC, or vehicle. B1R function was assessed using a tail-flick test after intrathecal (i.t. injection of a selective B1R agonist (des-Arg9-BK, and its microglial localization was investigated by confocal microscopy with the selective fluorescent B1R agonist, [Nα-bodipy]-des-Arg9-BK. The effect of i.t. capsaicin (1 μg/site was also investigated. Results Capsaicin (10 to 50 mg/kg, s.c. enhanced time-dependently (0-24h B1R mRNA levels in the lumbar spinal cord; this effect was prevented by capsazepine (10 mg/kg, i.p.; 10 μg/site, i.t. and SB-366791 (1 mg/kg, i.p.; 30 μg/site, i.t.. Increases of B1R mRNA were correlated with IL-1β mRNA levels, and they were significantly less in cervical and thoracic spinal cord. Intrathecal capsaicin (1 μg/site also enhanced B1R mRNA in lumbar spinal cord. NAC (1 g/kg/d × 7 days prevented B1R up-regulation, superoxide anion production and NF-kB activation induced by capsaicin (15 mg/kg. Des-Arg9-BK (9.6 nmol/site, i.t. decreased by 25-30% the nociceptive threshold at 1 min post-injection in capsaicin-treated rats (10-50 mg/kg while it was without effect in control rats. Des-Arg9-BK-induced thermal hyperalgesia was blocked by capsazepine, SB-366791 and by antagonists/inhibitors of B1R (SSR240612, 10 mg/kg, p

  16. [Effect of population density on enzymatic activity of antioxidative and phenol oxidase systems of imagoes and nymphs of the marble cockroach Nauphoeta cinerea].

    Science.gov (United States)

    Murzagulov, G S; Saltykova, E S; Gaĭfullina, L R; Nikolenko, A G

    2013-01-01

    The work deals with effect of density of population on functional activity of components pf protective system of adult individuals and nymphs of the marble cockroach. The resistance of individuals has been noted to decrease both at individual maintenance and under conditions of overpopulation. Changes in activities of enzymes of antioxidative and phenoloxidase systems are studied ion the insect hemolymph and intestine. Possible consequences of isolation and overpopulation are discussed both for stability and for individual development.

  17. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

    Directory of Open Access Journals (Sweden)

    Hirotaka Yamamoto

    2016-01-01

    Full Text Available Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders.

  18. Combined cadmium and elevated ozone affect concentrations of cadmium and antioxidant systems in wheat under fully open-air conditions

    International Nuclear Information System (INIS)

    Guo, Hongyan; Tian, Ran; Zhu, Jianguo; Zhou, Hui; Pei, Daping; Wang, Xiaorong

    2012-01-01

    Highlights: ► Combined effect of elevated O 3 and Cd levels on wheat was studied using the free-air concentration enrichment system. ► Elevated O 3 levels result in an increased concentration of Cd in wheat plants grown on Cd-contaminated soils. ► Combined cadmium and elevated O 3 have a significantly synergic effect on oxidative stress in wheat shoots. - Abstract: Pollution of the environment with both ozone (O 3 ) and heavy metals has been steadily increasing. An understanding of their combined effects on plants, especially crops, is limited. Here we studied the effects of elevated O 3 on oxidative stress and bioaccumulation of cadmium (Cd) in wheat under Cd stress using a free-air concentration enrichment (FACE) system. In this field experiment in Jiangdu (Jiangsu Province, China), wheat plants were grown in pots containing soil with various concentrations of cadmium (0, 2, and 10 mg kg −1 Cd was added to the soil) under ambient conditions and under elevated O 3 levels (50% higher than the ambient O 3 ). Present results showed that elevated O 3 led to higher concentrations of Cd in wheat tissues (shoots, husk and grains) with respect to contaminated soil. Combined exposure to Cd and elevated O 3 levels strongly affected the antioxidant isoenzymes POD, APX and CAT and accelerated oxidative stress in wheat leaves. Our results suggest that elevated O 3 levels cause a reduction in food quality and safety.

  19. Antioxidant Systems from Pepper (Capsicum annuum L.): Involvement in the Response to Temperature Changes in Ripe Fruits

    Science.gov (United States)

    Mateos, Rosa M.; Jiménez, Ana; Román, Paloma; Romojaro, Félix; Bacarizo, Sierra; Leterrier, Marina; Gómez, Manuel; Sevilla, Francisca; del Río, Luis A.; Corpas, Francisco J.; Palma, José M.

    2013-01-01

    Sweet pepper is susceptible to changes in the environmental conditions, especially temperatures below 15 °C. In this work, two sets of pepper fruits (Capsicum annuum L.) which underwent distinct temperature profiles in planta were investigated. Accordingly, two harvesting times corresponding to each set were established: Harvest 1, whose fruits developed and ripened at 14.9 °C as average temperature; and Harvest 2, with average temperature of 12.4 °C. The oxidative metabolism was analyzed in all fruits. Although total ascorbate content did not vary between Harvests, a shift from the reduced to the oxidized form (dehydroascorbate), accompanied by a higher ascorbate peroxidase activity, was observed in Harvest 2 with respect to Harvest 1. Moreover, a decrease of the ascorbate-generating enzymatic system, the γ-galactono-lactone dehydrogenase, was found at Harvest 2. The activity values of the NADP-dependent dehydrogenases analyzed seem to indicate that a lower NADPH synthesis may occur in fruits which underwent lower temperature conditions. In spite of the important changes observed in the oxidative metabolism in fruits subjected to lower temperature, no oxidative stress appears to occur, as indicated by the lipid peroxidation and protein oxidation profiles. Thus, the antioxidative systems of pepper fruits seem to be involved in the response against temperature changes. PMID:23644886

  20. Response of antioxidant defense system to laser radiation apical meristem of Isatis indigotica seedlings exposed to UV-B.

    Science.gov (United States)

    Chen, Yi-Ping

    2009-07-01

    To determine the response of antioxidant defense system to laser radiation apical meristem of Isatis indigotica seedlings, Isatis indigotica seedlings were subjected to UV-B radiation (10.08 kJ m(-2)) for 8 h day(-1) for 8 days (PAR, 220 micromol m(-2) s(-1)) and then exposed to He-Ne laser radiation (633 nm; 5.23 mW mm(-2); beam diameter: 1.5 mm) for 5 min each day without ambient light radiation. Changes in free radical elimination systems were measured, the results indicate that: (1) UV-B radiation enhanced the concentration of Malondialdahyde (MDA) and decreased the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) in seedlings compared with the control. The concentration of MDA was decreased and the activities of SOD, CAT and POD were increased when seedlings were subjected to elevated UV-B damage followed by laser; (2) the concentration of UV absorbing compounds and proline were increased progressively with UV-B irradiation, laser irradiation and He-Ne laser irradiation plus UV-B irradiation compared with the control. These results suggest that laser radiation has an active function in repairing UV-B-induced lesions in seedlings.

  1. Effects of different rearing and feeding systems on lipid oxidation and antioxidant capacity of freeze-dried egg yolks.

    Science.gov (United States)

    Pignoli, Giovanni; Rodriguez-Estrada, Maria Teresa; Mandrioli, Mara; Barbanti, Lorenzo; Rizzi, Laura; Lercker, Giovanni

    2009-12-23

    Lipid oxidation and antioxidant capacity of freeze-dried egg yolks produced with two rearing systems (battery cages and free-range) and two types of feedings (conventional and organic) were studied. Nine fresh egg yolks of each crossed treatment were pooled, frozen for a month, freeze-dried, vacuum-packed, and kept at -18 degrees C until analysis. No significant differences were observed in the lipid (58.0-62.1%) and total sterol contents (33.0-35.5 g/kg of lipids) of the freeze-dried egg yolks. Free rearing and conventional feeding systems resulted in significantly higher total tocopherol, alpha-tocopherol, and lutein contents, as compared to the battery cage and the organic feed, respectively. However, no significant differences were found in lipid oxidation (peroxide value = 0.7-0.9 mequiv of O(2)/kg of fat; thiobarbituric reactive substances = 1.0-1.3 mg of malonylaldehyde/kg of sample) and cholesterol oxidation (28.8-43.5 mg of cholesterol oxidation products/kg of lipids; 0.08-0.12% oxidized cholesterol) of freeze-dried egg yolks except for 7alpha-hydroxycholesterol, which was significantly lower in samples obtained with organic feed.

  2. Oxidation in fish-oil-enriched mayonnaise 2 : Assessment of the efficacy of different tocopherol antioxidant systems by discriminant partial least squares regression analysis

    DEFF Research Database (Denmark)

    Jacobsen, Charlotte; Hartvigsen, Karsten; Lund, Pia

    2000-01-01

    . The rheological and structural properties of the mayonnaise were also affected by the addition of extra emulsifier, but this did not influence the formation of fishy and rancid off-flavours. Addition of the A system caused the immediate formation of distinct fish; and rancid off-flavours in the fresh mayonnaises......Oxidative protection of mayonnaises with 16% fish oil was studied during cold storage (5 degrees C) after supplementation with different tocopherol systems: the ternary antioxidant system ascorbic acid, lecithin and tocopherol (A/L/T), and two commercial mixtures, an oil-soluble (Toco 70......) preparation and a water-soluble (Grindox 1032) preparation, The physical structure of the fish-oil-enriched mayonnaise was manipulated by adding extra emulsifier (Panodan TR) with the purpose of investigating whether or not this affected the antioxidative activity of the tocopherol mixtures. A number...

  3. Exploring the role of microglia in mood disorders associated with experimental multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Antonietta eGentile

    2015-06-01

    Full Text Available Microglia is increasingly recognized to play a crucial role in the pathogenesis of psychiatric diseases. In particular, microglia may be the cellular link between inflammation and behavioural alterations: by releasing a number of soluble factors, among which pro-inflammatory cytokines, they can regulate synaptic activity, thereby leading to perturbation of behaviour.In multiple sclerosis (MS, the most common neuroinflammatory disorder affecting young adults, microglia activation and dysfunction may account for mood symptoms, like depression and anxiety, that are often diagnosed in patients even in the absence of motor disability. Behavioural studies in experimental autoimmune encephalomyelitis (EAE, the animal model of MS, have shown that emotional changes occur early in the disease and in correlation to inflammatory mediator and neurotransmitter level alterations. However, such studies lack a full and comprehensive analysis of the role played by microglia in EAE-behavioural syndrome. We review the experimental studies addressing behavioural symptoms in EAE, and propose the study of neuron-glia interaction as a powerful but still poorly explored tool to investigate the burden of microglia in mood alterations associated to MS.

  4. Astroglia-Microglia Cross Talk during Neurodegeneration in the Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Montserrat Batlle

    2015-01-01

    Full Text Available Brain injury triggers a progressive inflammatory response supported by a dynamic astroglia-microglia interplay. We investigated the progressive chronic features of the astroglia-microglia cross talk in the perspective of neuronal effects in a rat model of hippocampal excitotoxic injury. N-Methyl-D-aspartate (NMDA injection triggered a process characterized within 38 days by atrophy, neuronal loss, and fast astroglia-mediated S100B increase. Microglia reaction varied with the lesion progression. It presented a peak of tumor necrosis factor-α (TNF-α secretion at one day after the lesion, and a transient YM1 secretion within the first three days. Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values. To further investigate the astroglia role in the microglia reaction, we performed concomitant transient astroglia ablation with L-α-aminoadipate and NMDA-induced lesion. We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression. S100B reactivity only increased after astroglia recovery. Our results argue for an initial neuroprotective microglial reaction, with a direct astroglial control of the microglial cytotoxic response. We propose the recovery of the astroglia-microglia cross talk as a tissue priority conducted to ensure a proper cellular coordination that retails brain damage.

  5. Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain

    Directory of Open Access Journals (Sweden)

    Katharine Askew

    2017-01-01

    Full Text Available Summary: Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing the whole population to be renewed several times during a lifetime. The number of microglial cells remains steady from late postnatal stages until aging and is maintained by the spatial and temporal coupling of proliferation and apoptosis, as shown by pulse-chase studies, chronic in vivo imaging of microglia, and the use of mouse models of dysregulated apoptosis. Our results reveal that the microglial population is constantly and rapidly remodeled, expanding our understanding of its role in the maintenance of brain homeostasis. : The mechanism or mechanisms underlying microglial homeostasis are unknown. Askew et al. show that microglia self-renewal is maintained by coupled proliferation and apoptosis, resulting in a stable microglia number over a mouse or human lifetime. Keywords: self-renewal, BrdU, CSF1R, CX3CR1, Macgreen, Vav-Bcl2, RNA-seq

  6. Vascular consequences of passive Aβ immunization for Alzheimer's disease. Is avoidance of "malactivation" of microglia enough?

    Directory of Open Access Journals (Sweden)

    Barger Steven W

    2005-01-01

    Full Text Available Abstract The role of inflammation in Alzheimer's disease (AD has been controversial since its first consideration. As with most instances of neuroinflammation, the possibility must be considered that activation of glia and cytokine networks in AD arises merely as a reaction to neurodegeneration. Active, healthy neurons produce signals that suppress inflammatory events, and dying neurons activate phagocytic responses in microglia at the very least. But simultaneous with the arrival of a more complex view of microglia, evidence that inflammation plays a causal or exacerbating role in AD etiology has been boosted by genetic, physiological, and epidemiological studies. In the end, it may be that the semantics of "inflammation" and glial "activation" must be regarded as too simplistic for the advancement of our understanding in this regard. It is clear that elaboration of the entire repertoire of activated microglia – a phenomenon that may be termed "malactivation" – must be prevented for healthy brain structure and function. Nevertheless, recent studies have suggested that phagocytosis of Aβ by microglia plays an important role in clearance of amyloid plaques, a process boosted by immunization paradigms. To the extent that this clearance might produce clinical improvements (still an open question, this relationship thus obligates a more nuanced consideration of the factors that indicate and control the various activities of microglia and other components of neuroinflammation.

  7. Astroglia-Microglia Cross Talk during Neurodegeneration in the Rat Hippocampus

    Science.gov (United States)

    Batlle, Montserrat; Ferri, Lorenzo; Andrade, Carmen; Ortega, Francisco-Javier; Vidal-Taboada, Jose M.; Pugliese, Marco; Mahy, Nicole; Rodríguez, Manuel J.

    2015-01-01

    Brain injury triggers a progressive inflammatory response supported by a dynamic astroglia-microglia interplay. We investigated the progressive chronic features of the astroglia-microglia cross talk in the perspective of neuronal effects in a rat model of hippocampal excitotoxic injury. N-Methyl-D-aspartate (NMDA) injection triggered a process characterized within 38 days by atrophy, neuronal loss, and fast astroglia-mediated S100B increase. Microglia reaction varied with the lesion progression. It presented a peak of tumor necrosis factor-α (TNF-α) secretion at one day after the lesion, and a transient YM1 secretion within the first three days. Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values. To further investigate the astroglia role in the microglia reaction, we performed concomitant transient astroglia ablation with L-α-aminoadipate and NMDA-induced lesion. We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression. S100B reactivity only increased after astroglia recovery. Our results argue for an initial neuroprotective microglial reaction, with a direct astroglial control of the microglial cytotoxic response. We propose the recovery of the astroglia-microglia cross talk as a tissue priority conducted to ensure a proper cellular coordination that retails brain damage. PMID:25977914

  8. TNF-α from hippocampal microglia induces working memory deficits by acute stress in mice.

    Science.gov (United States)

    Ohgidani, Masahiro; Kato, Takahiro A; Sagata, Noriaki; Hayakawa, Kohei; Shimokawa, Norihiro; Sato-Kasai, Mina; Kanba, Shigenobu

    2016-07-01

    The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-α levels were significantly elevated after acute stress, and acute stress-induced TNF-α was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-α were not elevated after acute stress. Etanercept (TNF-α inhibitor) recovered working memory deficits in accordance with hippocampal TNF-α reductions. Overall, results suggest that TNF-α from hippocampal microglia is a key contributor to early-stage stress-to-mental responses. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Responses of antioxidant systems after exposition to rare earths and their role in chilling stress in common duckweed (Lemna minor L.): a defensive weapon or a boomerang?

    Science.gov (United States)

    Ippolito, M P; Fasciano, C; d'Aquino, L; Morgana, M; Tommasi, F

    2010-01-01

    Extensive agriculture application of rare earth elements (REEs) in Far East countries might cause spreading of these metals in aquatic and terrestrial ecosystems, thus inducing a growing concern about their environmental impact. In this work the effects of a mix of different REE nitrate (RE) and of lanthanum nitrate (LA) on catalase and antioxidant systems involved in the ascorbate-glutathione cycle were investigated in common duckweed Lemna minor L. The results indicated that L. minor shows an overall good tolerance to the presence of REEs in the media. Treatments at concentrations up to 5 mM RE and 5 mM LA did not cause either visible symptoms on plants or significant effects on reactive oxygen species (ROS) production, chlorophyll content, and lipid peroxidation. Toxic effects were observed after 5 days of exposition to 10 mM RE and 10 mM LA. A remarkable increase in glutathione content as well as in enzymatic antioxidants was observed before the appearance of the stress symptoms in treated plants. Duckweed plants pretreated with RE and LA were also exposed to chilling stress to verify whether antioxidants variations induced by RE and LA improve plant resistance to the chilling stress. In pretreated plants, a decrease in ascorbate and glutathione redox state and in chlorophyll content and an increase in lipid peroxidation and ROS production levels were observed. The use of antioxidant levels as a stress marker for monitoring REE toxicity in aquatic ecosystems by means of common duckweed is discussed.

  10. Influence of the PDE5 inhibitor tadalafil on redox status and antioxidant defense system in C2C12 skeletal muscle cells.

    Science.gov (United States)

    Duranti, Guglielmo; Ceci, Roberta; Sgrò, Paolo; Sabatini, Stefania; Di Luigi, Luigi

    2017-05-01

    Phosphodiesterase type 5 inhibitors (PDE5Is), widely known for their beneficial effects onto male erectile dysfunction, seem to exert favorable effects onto metabolism as well. Tadalafil exposure increases oxidative metabolism of C2C12 skeletal muscle cells. A rise in fatty acid (FA) metabolism, requiring more oxygen, could induce a larger reactive oxygen species (ROS) release as a byproduct thus leading to a redox imbalance. The aim of this study was to determine how PDE5I tadalafil influences redox status in skeletal muscle cells to match the increasing oxidative metabolism. To this purpose, differentiated C2C12 skeletal muscle cells were treated with tadalafil and analyzed for total antioxidant capacity (TAC) and glutathione levels as marker of redox status; enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) engaged in antioxidant defense; and lipid peroxidation (TBARS) and protein carbonyls (PrCar) as markers of oxidative damage. Tadalafil increased total intracellular glutathione (tGSH), CAT, SOD, and GPx enzymatic activities while no changes were found in TAC. A perturbation of redox status, as showed by the decrease in the ratio between reduced/oxidized glutathione (GSH/GSSG), was observed. Nevertheless, it did not cause any change in TBARS and PrCar levels probably due to the enhancement in the antioxidant enzymatic network. Taken together, these data indicate that tadalafil, besides improving oxidative metabolism, may be beneficial to skeletal muscle cells by enhancing the enzymatic antioxidant system capacity.

  11. The state of lipid peroxidation and the antioxidant system in victims of the Chernobyl accident that suffer from duodenal ulcer

    International Nuclear Information System (INIS)

    Kucherenko, M.Je.; Drobyins'ka, O.V.; Ostapchenko, L.Yi.

    2002-01-01

    In the bioptates of mucous membranes of stomach in peptic ulcer patients residing in the regions with a high level of contamination by radionuclides, a high level of products of lipid peroxidation is found. It is experimentally proved that the violations are accompanied by a significant fall of the level of antioxidant enzymes and warrant a wide use of direct antioxidant medicine to normalize all the above-mentioned processes

  12. Antioxidants in Raspberry: On-line analysis links antioxidant activity to a diversity of individual metabolites

    NARCIS (Netherlands)

    Beekwilder, M.J.; Jonker, H.H.; Hall, R.D.; Meer, van der I.M.; Vos, de C.H.

    2005-01-01

    The presence of antioxidant compounds can be considered as a quality parameter for edible fruit. In this paper, we studied the antioxidant compounds in raspberry (Rubus idaeus) fruits by high-performance liquid chromatography (HPLC) coupled to an on-line postcolumn antioxidant detection system. Both

  13. Strategies to increase the activity of microglia as efficient protectors of the brain against infections

    Directory of Open Access Journals (Sweden)

    Roland eNau

    2014-05-01

    Full Text Available In healthy individuals, infections of the CNS are comparatively rare. Based on the ability of microglial cells to phagocytose and kill pathogens and on clinical findings in immunocompromized patients with CNS infections, we hypothesize that an intact microglial function is crucial to protect the brain from infections. Phagocytosis of pathogens by microglial cells can be stimulated by agonists of receptors of the innate immune system. Enhancing this pathway to increase the resistance of the brain to infections entails the risk of inducing collateral damage to the nervous tissue. The diversity of microglial cells opens avenue to selectively stimulate sub-populations responsible for the defence against pathogens without stimulating sub-populations which are responsible for collateral damage to the nervous tissue. Palmitoylethanolamide (PEA, an endogenous lipid, increased phagocytosis of bacteria by microglial cells in vitro without a measurable proinflammatory effect. It was tested clinically apparently without severe side effects. Glatiramer acetate increased phagocytosis of latex beads by microglia and monocytes, and dimethyl fumarate enhanced elimination of human immunodeficiency virus from infected macrophages without inducing a release of proinflammatory compounds. Therefore, the discovery of compounds which stimulate the elimination of pathogens without collateral damage of neuronal structures appears an achievable goal. PEA and, with limitations, glatiramer acetate and dimethyl fumarate appear promising candidates.

  14. Aquaporin-4 mediates communication between astrocyte and microglia: Implications of neuroinflammation in experimental Parkinson's disease.

    Science.gov (United States)

    Sun, H; Liang, R; Yang, B; Zhou, Y; Liu, M; Fang, F; Ding, J; Fan, Y; Hu, G

    2016-03-11

    Aquaporin-4 (AQP4), a water-selective membrane transport protein, is up-regulated in astrocytes in various inflammatory lesions, including Parkinson disease (PD). However, the exact functional roles of AQP4 in neuroinflammation remain unknown. In the present study, we investigated how AQP4 participates in the neuroinflammation of PD using AQP4 knockout (KO) mice and astrocyte-microglial co-cultures. We found that AQP4 KO mice exhibited increased basal and inducible canonical NF-κB activity, and showed significantly enhanced gliosis (astrocytosis and microgliosis) in chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)/probenecid PD models, companying with the increase in the production of IL-1β and TNF-α in the midbrain. Similarly, AQP4 deficiency augmented the activation of the NF-κB pathway and the production of IL-1β and TNF-α in midbrain astrocyte cultures treated with MPP(+) (1-methyl-4-phenylpyridinium). Furthermore, AQP4 deficiency promoted activation of microglial cells in the co-cultured system. Our data provide the first evidence that AQP4 modulates astrocyte-to-microglia communication in neuroinflammation, although its effect on astrocyte inflammatory activation remains to be explored. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Response of the physiological parameters of mango fruit (transpiration, water relations and antioxidant system) to its light and temperature environment.

    Science.gov (United States)

    Léchaudel, Mathieu; Lopez-Lauri, Félicie; Vidal, Véronique; Sallanon, Huguette; Joas, Jacques

    2013-04-15

    Depending on the position of the fruit in the tree, mango fruit may be exposed to high temperature and intense light conditions that may lead to metabolic and physiological disorders and affect yield and quality. The present study aimed to determine how mango fruit adapted its functioning in terms of fruit water relations, epicarp characteristics and the antioxidant defence system in peel, to environmental conditions. The effect of contrasted temperature and light conditions was evaluated under natural solar radiation and temperature by comparing well-exposed and shaded fruit at three stages of fruit development. The sun-exposed and shaded peels of the two sides of the well-exposed fruit were also compared. Depending on fruit position within the canopy and on the side of a well-exposed fruit, the temperature gradient over a day affected fruit characteristics such as transpiration, as revealed by the water potential gradient as a function of the treatments, and led to a significant decrease in water conductance for well-exposed fruits compared to fruits within the canopy. Changes in cuticle thickness according to fruit position were consistent with those of fruit water conductance. Osmotic potential was also affected by climatic environment and harvest stage. Environmental conditions that induced water stress and greater light exposure, like on the sunny side of well-exposed fruit, increased the hydrogen peroxide, malondialdehyde and total and reduced ascorbate contents, as well as SOD, APX and MDHAR activities, regardless of the maturity stage. The lowest values were measured in the peel of the shaded fruit, that of the shaded side of well-exposed fruit being intermediate. Mango fruits exposed to water-stress-induced conditions during growth adapt their functioning by reducing their transpiration. Moreover, oxidative stress was limited as a consequence of the increase in antioxidant content and enzyme activities. This adaptive response of mango fruit to its

  16. Nitric oxide induced by polyamines involves antioxidant systems against chilling stress in tomato (Lycopersicon esculentum Mill.) seedling*#

    Science.gov (United States)

    Diao, Qian-Nan; Song, Yong-Jun; Shi, Dong-Mei; Qi, Hong-Yan

    2016-01-01

    Polyamines (PAs) and nitric oxide (NO) are vital signals in modulating plant response to abiotic stress. However, to our knowledge, studies on the relationship between NO and PAs in response to cold stress in tomato are limited. Accordingly, in this study, we investigated the effects of putrescine (Put) and spermidine (Spd) on NO generation and the function of Spd-induced NO in the tolerance of tomato seedling under chilling stress. Spd increased NO release via the nitric oxide synthase (NOS)-like and nitrate reductase (NR) enzymatic pathways in the seedlings, whereas Put had no such effect. Moreover, H2O2 might act as an upstream signal to stimulate NO production. Both exogenous NO donor (sodium nitroprusside (SNP)) and Spd enhanced chilling tolerance in tomato, thereby protecting the photosynthetic system from damage. Compared to chilling treatment alone, Spd enhanced the gene expressions of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and their enzyme activities in tomato leaves. However, a scavenger or inhibitor of NO abolished Spd-induced chilling tolerance and blocked the increased expression and activity due to Spd of these antioxidant enzymes in tomato leaves under chilling stress. The results showed that NO induced by Spd plays a crucial role in tomato’s response to chilling stress. PMID:27921397

  17. Nitric oxide induced by polyamines involves antioxidant systems against chilling stress in tomato (Lycopersicon esculentum Mill.) seedling.

    Science.gov (United States)

    Diao, Qian-Nan; Song, Yong-Jun; Shi, Dong-Mei; Qi, Hong-Yan

    Polyamines (PAs) and nitric oxide (NO) are vital signals in modulating plant response to abiotic stress. However, to our knowledge, studies on the relationship between NO and PAs in response to cold stress in tomato are limited. Accordingly, in this study, we investigated the effects of putrescine (Put) and spermidine (Spd) on NO generation and the function of Spd-induced NO in the tolerance of tomato seedling under chilling stress. Spd increased NO release via the nitric oxide synthase (NOS)-like and nitrate reductase (NR) enzymatic pathways in the seedlings, whereas Put had no such effect. Moreover, H 2 O 2 might act as an upstream signal to stimulate NO production. Both exogenous NO donor (sodium nitroprusside (SNP)) and Spd enhanced chilling tolerance in tomato, thereby protecting the photosynthetic system from damage. Compared to chilling treatment alone, Spd enhanced the gene expressions of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and their enzyme activities in tomato leaves. However, a scavenger or inhibitor of NO abolished Spd-induced chilling tolerance and blocked the increased expression and activity due to Spd of these antioxidant enzymes in tomato leaves under chilling stress. The results showed that NO induced by Spd plays a crucial role in tomato's response to chilling stress.

  18. Boron alleviates the aluminum toxicity in trifoliate orange by regulating antioxidant defense system and reducing root cell injury.

    Science.gov (United States)

    Riaz, Muhammad; Yan, Lei; Wu, Xiuwen; Hussain, Saddam; Aziz, Omar; Wang, Yuhan; Imran, Muhammad; Jiang, Cuncang

    2018-02-15

    Aluminium (Al) toxicity is the most important soil constraint for plant growth and development in acid soils (pH Boron (B) is an essential micronutrient for the growth and development of higher plants. The results of previous studies propose that B might ameliorate Al toxicity; however, none of the studies have been conducted on trifoliate orange to study this effect. Thus, a study was carried out in hydroponics comprising of two different Al concentrations, 0 and 400 μM. For every concentration, two B treatments (0 and 10 μM as H 3 BO 3 ) were applied to investigate the B-induced alleviation of Al toxicity and exploring the underneath mechanisms. The results revealed that Al toxicity under B deficiency severely hampered the root growth and physiology of plant, caused oxidative stress and membrane damage, leading to severe root injury and damage. However, application of B under Al toxicity improved the root elongation and photosynthesis, while reduced Al uptake and mobilization into plant parts. Moreover, B supply regulated the activities of antioxidant enzymes, proline, secondary metabolites (phenylalanine ammonia lyase and polyphenol oxidase) contents, and stabilized integrity of proteins. Our study results imply that B supply promoted root growth as well as defense system by reducing reactive oxygen species (ROS) and Al concentrations in plant parts thus B induced alleviation of Al toxicity; a fact that might be significant for higher productivity of agricultural plants grown in acidic conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Effects of florfenicol on the antioxidant status, detoxification system and biomolecule damage in the swimming crab (Portunus trituberculatus).

    Science.gov (United States)

    Ren, Xianyun; Wang, Zhuqing; Gao, Baoquan; Liu, Ping; Li, Jian

    2017-09-01

    Florfenicol (FLR) is the most commonly used antibacterial agent in aquaculture because of its wide spectrum of activity and few side-effects. We characterized the toxicokinetics of FLR in the swimming crab (Portunus trituberculatus) after intravenous (IV) dosing (20, 40 and 80mg/kg). The results showed that FLR significantly suppressed the antioxidant system of the hepatopancreas. FLR induced transcriptional expression of phase I and phase II detoxification genes (CYP3 and GST, respectively) in a dose- and clearance time-dependent manner and altered the expression of their corresponding enzymes (erythromycin N-demethylase and glutathione S-transferase, respectively). Moreover, FLR induced the transcription of ATP-binding cassette (ABC) transporter subfamily B (ABCB) and subfamily G (ABCG), although ABCG transcription was not induced by FLR at 20mg/kg. Additionally, higher FLR doses caused significant biomolecule damage during the first 48h after delivery. This study will provide an improved understanding of the exact mechanism underlying toxicity in aquatic organisms. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Manganese-induced cadmium stress tolerance in rice seedlings: Coordinated action of antioxidant defense, glyoxalase system and nutrient homeostasis.

    Science.gov (United States)

    Rahman, Anisur; Nahar, Kamrun; Hasanuzzaman, Mirza; Fujita, Masayuki

    The accumulation of cadmium (Cd) alters different physiological and biochemical attributes that affect plant growth and yield. In our study, we investigated the regulatory role of supplemental manganese (Mn) on hydroponically grown rice (Oryza sativa L. cv. BRRI dhan29) seedlings under Cd-stress conditions. Exposure of 14-d-old seedlings to 0.3mM CdCl 2 for three days caused growth inhibition, chlorosis, nutrient imbalance, and higher Cd accumulation. Higher Cd uptake caused oxidative stress through lipid peroxidation, loss of plasma membrane integrity, and overproduction of reactive oxygen species (ROS) and methylglyoxal (MG). The exogenous application of 0.3mM MnSO 4 to Cd-treated seedlings partly recovered Cd-induced water loss, chlorosis, growth inhibition, and nutrient imbalance by reducing Cd uptake and its further translocation to the upper part of the plant. Supplemental Mn also reduced Cd-induced oxidative damage and lipid peroxidation by improved antioxidant defense and glyoxalase systems through enhancing ROS and MG detoxification, respectively. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  1. The ability of in vitro antioxidant assays to predict the efficiency of a cod protein hydrolysate and brown seaweed extract to prevent oxidation in marine food model systems.

    Science.gov (United States)

    Jónsdóttir, Rósa; Geirsdóttir, Margrét; Hamaguchi, Patricia Y; Jamnik, Polona; Kristinsson, Hordur G; Undeland, Ingrid

    2016-04-01

    The ability of different in vitro antioxidant assays to predict the efficiency of cod protein hydrolysate (CPH) and Fucus vesiculosus ethyl acetate extract (EA) towards lipid oxidation in haemoglobin-fortified washed cod mince and iron-containing cod liver oil emulsion was evaluated. The progression of oxidation was followed by sensory analysis, lipid hydroperoxides and thiobarbituric acid-reactive substances (TBARS) in both systems, as well as loss of redness and protein carbonyls in the cod system. The in vitro tests revealed high reducing capacity, high DPPH radical scavenging properties and a high oxygen radical absorbance capacity (ORAC) value of the EA which also inhibited lipid and protein oxidation in the cod model system. The CPH had a high metal chelating capacity and was efficient against oxidation in the cod liver oil emulsion. The results indicate that the F. vesiculosus extract has a potential as an excellent natural antioxidant against lipid oxidation in fish muscle foods while protein hydrolysates are more promising for fish oil emulsions. The usefulness of in vitro assays to predict the antioxidative properties of new natural ingredients in foods thus depends on the knowledge about the food systems, particularly the main pro-oxidants present. © 2015 Society of Chemical Industry.

  2. Population control of resident and immigrant microglia by mitosis and apoptosis

    DEFF Research Database (Denmark)

    Wirenfeldt, Martin; Dissing-Olesen, Lasse; Babcock, Alicia

    2007-01-01

    microglia often occurred in clusters, some having recently incorporated bromodeoxyuridine, showing that proliferation had occurred. Annexin V labeling and staining for activated caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that apoptotic mechanisms participate...... in dissolution of the microglial response. Using bone marrow chimeric mice, we found that the lesion-induced proliferative capacity of resident microglia superseded that of immigrant microglia, whereas lesion-induced kinetics of apoptosis were comparable. Microglial numbers and responses were severely reduced...... in bone marrow chimeric mice. These results broaden our understanding of the microglial response to neural damage by demonstrating that simultaneously occurring mitosis and apoptosis regulate expansion and reduction of both resident and immigrant microglial cell populations....

  3. CpG-ODNs induces up-regulated expression of chemokine CCL9 in mouse macrophages and microglia

    Digital Repository Service at National Institute of Oceanography (India)

    Ravindran, C.; Cheng, Y.-C.; Liang, S.-M.

    G-ODNs on macrophage/microglial cells are investigated. CpG-ODNs enhanced the expression of TLR9 mRNA of RAW264.7 macrophage and BV2 microglia cells time dependently. The expression of CCL9 of macrophages/microglia showed different responsiveness upon stimulation...

  4. Anti-inflammatory effects of tanshinone IIA on radiation-induced microglia BV-2 cells inflammatory response

    DEFF Research Database (Denmark)

    Dong, Xiaorong; Dong, Jihua; Zhang, Ruiguang

    2009-01-01

    AIM: The aim of this study was to explore the inhibitory effects of Tanshinone II(A) on the production of proinflammation cytokines in radiation-stimulated microglia. METHODS: Microglia cells were treated with 2, 4, 8, 16, and 32 Gy of irradiation or sham-irradiated in the presence or absence of ...

  5. 6-Mercaptopurine attenuates tumor necrosis factor-α production in microglia through Nur77-mediated transrepression and PI3K/Akt/mTOR signaling-mediated translational regulation.

    Science.gov (United States)

    Huang, Hsin-Yi; Chang, Hui-Fen; Tsai, Ming-Jen; Chen, Jhih-Si; Wang, Mei-Jen

    2016-04-13

    The pathogenesis of several neurodegenerative diseases often involves the microglial activation and associated inflammatory processes. Activated microglia release pro-inflammatory factors that may be neurotoxic. 6-Mercaptopurine (6-MP) is a well-established immunosuppressive drug. Common understanding of their immunosuppressive properties is largely limited to peripheral immune cells. However, the effect of 6-MP in the central nervous system, especially in microglia in the context of neuroinflammation is, as yet, unclear. Tumor necrosis factor-α (TNF-α) is a key cytokine of the immune system that initiates and promotes neuroinflammation. The present study aimed to investigate the effect of 6-MP on TNF-α production by microglia to discern the molecular mechanisms of this modulation. Lipopolysaccharide (LPS) was used to induce an inflammatory response in cultured primary microglia or murine BV-2 microglial cells. Released TNF-α was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression was determined by real-time reverse transcription polymerase chain reaction (RT-PCR). Signaling molecules were analyzed by western blotting, and activation of NF-κB was measured by ELISA-based DNA binding analysis and luciferase reporter assay. Chromatin immunoprecipitation (ChIP) analysis was performed to examine NF-κB p65 and coactivator p300 enrichments and histone modifications at the endogenous TNF-α promoter. Treatment of LPS-activated microglia with 6-MP significantly attenuated TNF-α production. In 6-MP pretreated microglia, LPS-induced MAPK signaling, IκB-α degradation, NF-κB p65 nuclear translocation, and in vitro p65 DNA binding activity were not impaired. However, 6-MP suppressed transactivation activity of NF-κB and TNF-α promoter by inhibiting phosphorylation and acetylation of p65 on Ser276 and Lys310, respectively. ChIP analyses revealed that 6-MP dampened LPS-induced histone H3 acetylation of chromatin surrounding the TNF-α promoter

  6. Kynurenine pathway metabolic balance influences microglia activity: Targeting kynurenine monooxygenase to dampen neuroinflammation.

    Science.gov (United States)

    Garrison, Allison M; Parrott, Jennifer M; Tuñon, Arnulfo; Delgado, Jennifer; Redus, Laney; O'Connor, Jason C

    2018-08-01

    Chronic stress or inflammation increases tryptophan metabolism along the kynurenine pathway (KP), and the generation of neuroactive kynurenine metabolites contributes to subsequent depressive-like behaviors. Microglia regulate KP balance by preferentially producing oxidative metabolites, including quinolinic acid. Research has focused on the interplay between cytokines and HPA axis-derived corticosteroids in regulating microglial activity and effects of KP metabolites directly on neurons; however, the potential role that KP metabolites have directly on microglial activity is unknown. Here, murine microglia were stimulated with lipopolysaccharide(LPS). After 6 h, mRNA expression of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α and inducible nitric oxide synthase(iNOS) was dose-dependently increased along with the rate-limiting enzymes for oxidative KP metabolism, indoleamine-2,3-dioxygenase(IDO)-1 and kynurenine 3-monooxygenase(KMO). By 24 h post-LPS, kynurenine and quinolinic acid in the media was elevated. Inhibiting KMO with Ro 61-8048 during LPS challenge attenuated extracellular nitrite accumulation and expression of KMO and TNF-α in response to LPS. Similarly, primary microglia isolated from KMO -/- mice exhibited a significantly reduced pro-inflammatory response to LPS compared to WT controls. To determine whether the substrate (kynurenine) or end product (quinolinic acid) of KMO-dependent metabolism modulates the LPS response, microglia were treated with increasing concentrations of L-kynurenine or quinolinic acid in combination with LPS or saline. Interestingly, quinolinic acid did not impact the microglial LPS response. However, L-kynurenine had dose-dependent inhibitory effect on the LPS response. These data are the first to show an anti-inflammatory effect of KMO inhibition on microglia during immune challenge and suggest that KP metabolic balance may play a direct role in regulating microglia activity. Published by Elsevier Ltd.

  7. Microglia modulate hippocampal neural precursor activity in response to exercise and aging.

    Science.gov (United States)

    Vukovic, Jana; Colditz, Michael J; Blackmore, Daniel G; Ruitenberg, Marc J; Bartlett, Perry F

    2012-05-09

    Exercise has been shown to positively augment adult hippocampal neurogenesis; however, the cellular and molecular pathways mediating this effect remain largely unknown. Previous studies have suggested that microglia may have the ability to differentially instruct neurogenesis in the adult brain. Here, we used transgenic Csf1r-GFP mice to investigate whether hippocampal microglia directly influence the activation of neural precursor cells. Our results revealed that an exercise-induced increase in neural precursor cell activity was mediated via endogenous microglia and abolished when these cells were selectively removed from hippocampal cultures. Conversely, microglia from the hippocampi of animals that had exercised were able to activate latent neural precursor cells when added to neurosphere preparations from sedentary mice. We also investigated the role of CX(3)CL1, a chemokine that is known to provide a more neuroprotective microglial phenotype. Intraparenchymal infusion of a blocking antibody against the CX(3)CL1 receptor, CX(3)CR1, but not control IgG, dramatically reduced the neurosphere formation frequency in mice that had exercised. While an increase in soluble CX(3)CL1 was observed following running, reduced levels of this chemokine were found in the aged brain. Lower levels of CX(3)CL1 with advancing age correlated with the natural decline in neural precursor cell activity, a state that could be partially alleviated through removal of microglia. These findings provide the first direct evidence that endogenous microglia can exert a dual and opposing influence on neural precursor cell activity within the hippocampus, and that signaling through the CX(3)CL1-CX(3)CR1 axis critically contributes toward this process.

  8. [Knockdown of PRDX6 in microglia reduces neuron viability after OGD/R injury].

    Science.gov (United States)

    Tan, Li; Zhao, Yong; Jiang, Beibei; Yang, Bo; Zhang, Hui

    2016-08-01

    Objective To observe the effects of peroxiredoxin 6 (PRDX6) knockdown in the microglia on neuron viability after oxygen-glucose deprivation and reoxygenation (OGD/R). Methods Microglia was treated with lentivirus PRDX6-siRNA and Ca(2+)-independent phospholipase A2 (iPLA2) inhibitor, 1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol (MJ33). Twenty-four hours later, it was co-cultured with primary neuron to establish the microglia-neuron co-culture OGD/R model. According to the different treatment of microglia, the cells were divided into normal group, OGD/R group, negative control-siRNA treated OGD/R group, PRDX6-siRNA treated OGD/R group and PRDX6-siRNA combined with MJ33 treated OGD/R group. Western blot analysis and real-time quantitative PCR were respectively performed to detect PRDX6 protein and mRNA levels after knockdown of PRDX6 in microglia. The iPLA2 activity was measured by ELISA. MTS and lactate dehydrogenase (LDH) assay were used to measure neuron viability and cell damage. The oxidative stress level of neuron was determined by measuring superoxide dismutase (SOD) and malonaldehyde (MDA) content. Results In PRDX6-siRNA group, neuron viability was inhibited and oxidative stress damage was aggravated compared with OGD/R group. In PRDX6-siRNA combined with MJ33 group, cell viability was promoted and oxidative stress damage was alleviated compared with PRDX6-siRNA group. Conclusion PRDX6 in microglia protects neuron against OGD/R-induced injury, and iPLA2 activity has an effect on PRDX6.

  9. Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase-activating polypeptide against hydrogen peroxide-induced oxidative damages in cultured rat astrocytes.

    Science.gov (United States)

    Douiri, Salma; Bahdoudi, Seyma; Hamdi, Yosra; Cubì, Roger; Basille, Magali; Fournier, Alain; Vaudry, Hubert; Tonon, Marie-Christine; Amri, Mohamed; Vaudry, David; Masmoudi-Kouki, Olfa

    2016-06-01

    Astroglial cells possess an array of cellular defense mechanisms, including superoxide dismutase (SOD) and catalase antioxidant enzymes, to prevent damages caused by oxidative stress. Nevertheless, astroglial cell viability and functionality can be affected by significant oxidative stress. We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent glioprotective agent that prevents hydrogen peroxide (H2 O2 )-induced apoptosis in cultured astrocytes. The purpose of this study was to investigate the potential protective effect of PACAP against oxidative-generated alteration of astrocytic antioxidant systems. Incubation of cells with subnanomolar concentrations of PACAP inhibited H2 O2 -evoked reactive oxygen species accumulation, mitochondrial respiratory burst, and caspase-3 mRNA level increase. PACAP also stimulated SOD and catalase activities in a concentration-dependent manner, and counteracted the inhibitory effect of H2 O2 on the activity of these two antioxidant enzymes. The protective action of PACAP against H2 O2 -evoked inhibition of antioxidant systems in astrocytes was protein kinase A, PKC, and MAP-kinase dependent. In the presence of H2 O2 , the SOD blocker NaCN and the catalase inhibitor 3-aminotriazole, both suppressed the protective effects of PACAP on SOD and catalase activities, mitochondrial function, and cell survival. Taken together, these results indicate that the anti-apoptotic effect of PACAP on astroglial cells can account for the activation of endogenous antioxidant enzymes and reduction in respiration rate, thus preserving mitochondrial integrity and preventing caspase-3 expression provoked by oxidative stress. Considering its powerful anti-apoptotic and anti-oxidative properties, the PACAPergic signaling system should thus be considered for the development of new therapeutical approaches to cure various pathologies involving oxidative neurodegeneration. We propose the following cascade for the

  10. Effects of melatonin injection or green-wavelength LED light on the antioxidant system in goldfish (Carassius auratus) during thermal stress.

    Science.gov (United States)

    Jung, Seo Jin; Choi, Young Jae; Kim, Na Na; Choi, Ji Yong; Kim, Bong-Seok; Choi, Cheol Young

    2016-05-01

    We tested the mitigating effects of melatonin injections or irradiation from green-wavelength light-emitting diodes (LEDs) on goldfish (Carassius auratus) exposed to thermal stress (high water temperature, 30 °C). The effects of the two treatments were assessed by measuring the expression and activity levels of the antioxidant enzymes, superoxide dismutase and catalase, plasma hydrogen peroxide, lipid hydroperoxide, and lysozyme. In addition, a comet assay was conducted to confirm that high water temperature damaged nuclear DNA. The expression and activity of the antioxidant enzymes, plasma hydrogen peroxide, and lipid hydroperoxide were significantly higher after exposure to high temperature and were significantly lower in fish that received melatonin or LED light than in those that received no mitigating treatment. Plasma lysozyme was significantly lower after exposure to high temperature and was significantly higher after exposure to melatonin or LED light. The comet assay revealed that thermal stress caused a great deal of damage to nuclear DNA; however, treatment with melatonin or green-wavelength LED light prevented a significant portion of this damage from occurring. These results indicate that, although high temperatures induce oxidative stress and reduce immune system strength in goldfish, both melatonin and green-wavelength LED light inhibit oxidative stress and boost the immune system. LED treatment increased the antioxidant and immune system activity more significantly than did melatonin treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration.

    Science.gov (United States)

    Scholz, Rebecca; Sobotka, Markus; Caramoy, Albert; Stempfl, Thomas; Moehle, Christoph; Langmann, Thomas

    2015-11-17

    Microglia reactivity is a hallmark of retinal degenerations and overwhelming microglial responses contribute to photoreceptor death. Minocycline, a semi-synthetic tetracycline analog, has potent anti-inflammatory and neuroprotective effects. Here, we investigated how minocycline affects microglia in vitro and studied its immuno-modulatory properties in a mouse model of acute retinal degeneration using bright white light exposure. LPS-treated BV-2 microglia were stimulated with 50 μg/ml minocycline for 6 or 24 h, respectively. Pro-inflammatory gene transcription was determined by real-time RT-PCR and nitric oxide (NO) secretion was assessed using the Griess reagent. Caspase 3/7 levels were determined in 661W photoreceptors cultured with microglia-conditioned medium in the absence or presence of minocycline supplementation. BALB/cJ mice received daily intraperitoneal injections of 45 mg/kg minocycline, starting 1 day before exposure to 15.000 lux white light for 1 hour. The effect of minocycline treatment on microglial reactivity was analyzed by immunohistochemical stainings of retinal sections and flat-mounts, and messenger RNA (mRNA) expression of microglia markers was determined using real-time RT-PCR and RNA-sequencing. Optical coherence tomography (OCT) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainings were used to measure the extent of retinal degeneration and photoreceptor apoptosis. Stimulation of LPS-activated BV-2 microglia with minocycline significantly diminished the transcription of the pro-inflammatory markers CCL2, IL6, and inducible nitric oxide synthase (iNOS). Minocycline also reduced the production of NO and dampened microglial neurotoxicity on 661W photoreceptors. Furthermore, minocycline had direct protective effects on 661W photoreceptors by decreasing caspase 3/7 activity. In mice challenged with white light, injections of minocycline strongly decreased the number of amoeboid alerted microglia in the outer

  12. Vesicle-mediated transport and release of CCL21 in endangered neurons : A possible explanation for microglia activation remote from a primary lesion

    NARCIS (Netherlands)

    de Jong, EK; Dijkstra, IM; Hensens, M; Brouwer, N; van Amerongen, M; Liem, RSB; Boddeke, HWGM; Biber, K

    2005-01-01

    Whenever neurons in the CNS are injured, microglia become activated. In addition to local activation, microglia remote from the primary lesion site are stimulated. Because this so-called secondary activation of microglia is instrumental for long-term changes after neuronal injury, it is important to

  13. Evaluation of the antioxidant activity in food model system of fish peptides released during simulated gastrointestinal digestion

    DEFF Research Database (Denmark)

    Nieva-Echevarria, B.; Jacobsen, Charlotte; García Moreno, Pedro Jesús

    In the last decade, increasing evidences of the occurrence of lipid oxidation during digestion have been reported, in either in vivo or in vitro studies (1,2,3). As a result, the nutritional quality and safety of foodstuffs could be affected by the decrease of certain lipidic compounds of interest...... in the gastrointestinal tract. In fact, several studies have reported antioxidant activity of fish protein hydrolysates, coming from fish industry waste by-products (3,4). Thus, the potential release of peptides showing antioxidant properties during fish digestion cannot be ruled out. In order to shed light...... on these aspects, in vitro digestates of European sea bass were submitted to ultrafiltration using membranes with different cut off size. Afterwards, the potential antioxidant activity of the peptide fractions obtained was evaluated by comparing the oxidative stability of fish oil-in-water emulsions (5...

  14. Activity of the Antioxidant Defense System in a Typical Bioinsecticide-and Synthetic Insecticide-treated Cowpea Storage Beetle F. (Coleoptera: Chrysomelidae

    Directory of Open Access Journals (Sweden)

    Ayodele O. Kolawole

    2014-01-01

    Full Text Available The non-enzymatic and enzymatic antioxidant defense systems play a major role in detoxification of pro-oxidant endobiotics and xenobiotics. The possible involvement of beetle non-enzymatic [α-tocopherol, glutathione (GSH, and ascorbic acid] and enzymatic [catalase (CAT, superoxide dismutase (SOD, peroxidase (POX, and polyphenol oxidase (PPO] antioxidant defense system on the insecticidal activity of synthetic insecticides (cypermethrin, 2,2-dicholorovinyl dimethyl phosphate, and λ-cyhalothrin and ethanolic plant extracts of Tithonia diversifolia, Cyperus rotundus, Hyptis suaveolens leaves , and Jatropha Curcas seeds was investigated. 2,2-Dicholorovinyl dimethyl phosphate (DDVP; 200 ppm, LC 50 = 13.24 ppm and T. diversifolia (20,000 ppm resulted in 100% beetle mortality at 96-hour post-treatment. The post-treatments significantly increased the beetle α-tocopherol and GSH contents. Activities of CAT, SOD, POX, and PPO were modulated by the synthetic insecticides and bioinsecticides to diminish the adverse effect of the chemical stresses. Quantitative and qualitative allelochemical compositions of bioinsecticides and chemical structure of synthetic insecticides possibly account and for modulation of their respective enzyme activities. Altogether, oxidative stress was enormous enough to cause maladaptation in insects. This study established that oxidative imbalance created could be the molecular basis of the efficacy of both insecticides and bio-insecticides. Two, there was development of functional but inadequate antioxidant defense mechanism in the beetle.

  15. Cysteine-stabilised peptide extract of Morinda lucida (Benth) leaf exhibits antimalarial activity and augments antioxidant defense system in P. berghei-infected mice.

    Science.gov (United States)

    Adebayo, Joseph O; Adewole, Kayode E; Krettli, Antoniana U

    2017-07-31

    Cysteine-stabilised peptides (CSP) are majorly explored for their bioactivities with applications in medicine and agriculture. Morinda lucida leaf is used indigenously for the treatment of malaria; it also contains CSP but the role of CSP in the antimalarial activity of the leaf has not been evaluated. This study was therefore performed to evaluate the antimalarial activity of partially purified cysteine-stabilised peptide extract (PPCPE) of Morinda lucida leaf and its possible augmentation of the antioxidant systems of liver and erythrocytes in murine malaria. PPCPE was prepared from Morinda lucida leaf. The activity of PPCPE was evaluated in vitro against Plasmodium falciparum W2 and its cytotoxicity against a BGM kidney cell line. PPCPE was also evaluated for its antimalarial activity and its effects on selected liver and erythrocyte antioxidant parameters in P. berghei NK65-infected mice. PPCPE was not active against P. falciparum W2 (IC 50 : >50µg/ml) neither was it cytotoxic (MLD 50 : >1000µg/ml). However, PPCPE was active against P. berghei NK65 in vivo, causing 51.52% reduction in parasitaemia at 31.25mg/Kg body weight on day 4 post-inoculation. PPCPE significantly reduced (P activities of glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase in a dose-dependent manner, which was significant (P antimalarial effect and that PPCPE may augment the antioxidant defense system to alleviate the reactive oxygen species-mediated complications of malaria. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  16. Influence of stripe rust infection on the photosynthetic characteristics and antioxidant system of susceptible and resistant wheat cultivars at the adult plant stage.

    Science.gov (United States)

    Chen, Yang-Er; Cui, Jun-Mei; Su, Yan-Qiu; Yuan, Shu; Yuan, Ming; Zhang, Huai-Yu

    2015-01-01

    Wheat stripe rust (Puccinia striiformis f. sp. tritici, Pst), is one of the most serious diseases of wheat (Triticum aestivum L.) worldwide. To gain a better understanding of the protective mechanism against stripe rust at the adult plant stage, the differences in photosystem II and antioxidant enzymatic systems between susceptible and resistant wheat in response to stripe rust disease (P. striiformis) were investigated. We found that chlorophyll fluorescence and the activities of the antioxidant enzymes were higher in resistant wheat than in susceptible wheat after stripe rust infection. Compared with the susceptible wheat, the resistant wheat accumulated a higher level of D1 protein and a lower level of reactive oxygen species after infection. Furthermore, our results demonstrate that D1 and light-harvesting complex II (LHCII) phosphorylation are involved in the resistance to stripe rust in wheat. The CP29 protein was phosphorylated under stripe rust infection, like its phosphorylation in other monocots under environmental stresses. More extensive damages occur on the thylakoid membranes in the susceptible wheat compared with the resistant wheat. The findings provide evidence that thylakoid protein phosphorylation and antioxidant enzyme systems play important roles in plant responses and defense to biotic stress.

  17. [Correction of lipid peroxidation and antioxidant system disorders by bioflavonoids during modeling of cholesterol atherosclerosis in rabbits].

    Science.gov (United States)

    Shysh, A M; Pashevin, D O; Dosenko, V Ie; Moĭbenko, O O

    2011-01-01

    We have studied the influence of bioflavonoids (quercetin, corvitin) on lipid peroxidation and antioxidant enzymes in the modeling of cholesterol atherosclerosis in rabbits. It has been shown that simultaneous administration of the quercetin derivative corvitin suppressed lipid peroxidation. We showed that under hypercholesterolemia, the concentration of malone dialdehyde in myocardial tissue in rabbits is significantly increased, while administration of bioflavonoids decreased the concentration of malone dialdehyde by 38.3%. Furthermore, corvitin caused activating effects on antioxidant enzymes superoxide dismutase and catalase in cardiac tissue. Our data suggest that bioflavonoids are able to suppress lipid peroxidation and prevent the decrease ofantioxidant enzymes activity in rabbits with cholesterol-rich diet induced atherosclerosis.

  18. Data demonstrating the role of peroxiredoxin 2 as important anti-oxidant system in lung homeostasis

    Directory of Open Access Journals (Sweden)

    Enrica Federti

    2017-12-01

    Full Text Available The data presented in this article are related to the research paper entitled “peroxiredoxin-2 plays a pivotal role as multimodal cytoprotector in the early phase of pulmonary hypertension” (Federti et al., 2017 [1]. Data show that the absence of peroxiredoxin-2 (Prx2 is associated with increased lung oxidation and pulmonary vascular endothelial dysfunction. Prx2−/− mice displayed activation of the redox-sensitive transcriptional factors, NF-kB and Nrf2, and increased expression of cytoprotective system such as heme-oxygenase-1 (HO-1. We also noted increased expression of both markers of vascular activation and extracellular matrix remodeling. The administration of the recombinant fusion protein PEP Prx2 reduced the activation of NF-kB and Nrf2 and was paralleled by a decrease in HO-1 and in vascular endothelial abnormal activation. Prolonged hypoxia was used to trigger pulmonary artery hypertension (PAH. Prx2−/− precociously developed PAH compared to wildtype animals.

  19. Role of garlic oil and selenium as stimulators to some antioxidant defense system in irradiated male rats

    International Nuclear Information System (INIS)

    El-Gawish, M.A.; Abdel-Azeem, M.G.

    2002-01-01

    The increased level of lipid peroxide product; malondialdehyde (MDA) in various tissues of irradiated animals, may play a crucial role in damaging effects of exposure to ionizing radiation mediated by reactive free radicals generation. The protective efficiency of oral administration of garlic oil (500 mg/kg b.wt) three times weekly together with a single intraperitoneal injection of selenium (0.5 mg/kg b.wt) weekly for two weeks was examined on some antioxidant defense system as well as ultrastructural study in rats subjected to fractionated doses of gamma radiation up to a dose level of 6 Gy (1.5 Gy day after day). Exposure to gamma radiation induced a significant elevation in the level of malondialdehyde in plasma and liver and non-significant change was observed in superoxide dismutase activity (SOD). Also a significant increase was occurred in hepatic glutathione (GSH) content and glutathione peroxidase (GSHPx) activity. The pretreatment of irradiated rats with garlic oil and selenium caused a significant decrease in elevated level of MDA and a significant increase in the activity of SOD, GSHPx and GSH contents in both blood and liver. Concerning the ultrastructure studies, liver of irradiated rats showed abnormal shape of nucleus and nucleus membrane, swollen mitochondria with ruptured cristae, rupture of endoplasmic reticulum and vaculated cytoplasm, while intestine of irradiated rats exhibited deformed, shortened and abnormal structure of microvilli, accumulation of nuclear chromatin and dilatation of terminal web layer. In group of rats treated with garlic oil and selenium before exposure to gamma radiation, noticeable amelioration in ultrastructure changes of liver and intestine induced by irradiation was observed indicating a beneficial radioprotective role of both garlic oil and selenium

  20. Modulatory Effects of Exogenously Applied Polyamines on Postharvest Physiology, Antioxidant System and Shelf Life of Fruits: A Review.

    Science.gov (United States)

    Sharma, Sunil; Pareek, Sunil; Sagar, Narashans Alok; Valero, Daniel; Serrano, Maria

    2017-08-17

    Polyamines (PAs) are natural compounds involved in many growth and developmental processes in plants, and, specifically in fruits, play a vital role regulating its development, ripening and senescence processes. Putrescine (PUT), spermine (SPE), and spermidine (SPD) are prominent PAs applied exogenously to extend shelf life of fruits. They also originate endogenously during developmental phases of horticultural crops and simultaneously affect the quality attributes and shelf life. Their anti-ethylene nature is being exploited to enhance the shelf life when exogenously applied on fruits. In growth and development of fruits, PA levels generally fall, which marks the beginning of senescence at postharvest phase. PUT, SPE and SPD treatments are being applied during postharvest phase to prolong the shelf life. They enhance the shelf life of fruits by reducing respiration rate, ethylene release and enhance firmness and quality attributes in fruits. PAs have a mitigating impact on biotic and abiotic stresses including chilling injury (CI) in tropical and sub-tropical fruits. PAs are environment friendly in nature and are biodegradable without showing any negative effect on environment. Biotechnological interventions by using chimeric gene constructs of PA encoding genes has boosted the research to develop transgenic fruits and vegetables which would possess inherent or in situ mechanism of enhanced biosynthesis of PAs at different stages of development and thereby will enhance the shelf life and quality in fruits. Internal and external quality attributes of fruits are improved by modulation of antioxidant system and by strengthening biophysical morphology of fruits by electrostatic interaction between PAs and phospholipids in the cell wall.

  1. Targeting the Renin–Angiotensin System Combined With an Antioxidant Is Highly Effective in Mitigating Radiation-Induced Lung Damage

    Energy Technology Data Exchange (ETDEWEB)

    Mahmood, Javed [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Jelveh, Salomeh [Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Zaidi, Asif [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Doctrow, Susan R. [Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts (United States); Medhora, Meetha [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Hill, Richard P., E-mail: hill@uhnres.utoronto.ca [Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

    2014-07-15

    Purpose: To investigate the outcome of suppression of the renin angiotensin system using captopril combined with an antioxidant (Eukarion [EUK]-207) for mitigation of radiation-induced lung damage in rats. Methods and Materials: The thoracic cavity of female Sprague-Dawley rats was irradiated with a single dose of 11 Gy. Treatment with captopril at a dose of 40 mg/kg/d in drinking water and EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week after irradiation (PI) and continuing until 14 weeks PI. Breathing rate was monitored until the rats were killed at 32 weeks PI, when lung fibrosis was assessed by lung hydroxyproline content. Lung levels of the cytokine transforming growth factor-β1 and macrophage activation were analyzed by immunohistochemistry. Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine levels, and lipid peroxidation was measured by a T-BARS assay. Results: The increase in breathing rate in the irradiated rats was significantly reduced by the drug treatments. The drug treatment also significantly decreased the hydroxyproline content, 8-hydroxy-2-deoxyguanosine and malondialdehyde levels, and levels of activated macrophages and the cytokine transforming growth factor-β1 at 32 weeks. Almost complete mitigation of these radiation effects was observed by combining captopril and EUK-207. Conclusion: Captopril and EUK-207 can provide mitigation of radiation-induced lung damage out to at least 32 weeks PI after treatment given 1-14 weeks PI. Overall the combination of captopril and EUK-207 was more effective than the individual drugs used alone.

  2. Adverse effects of MWCNTs on life parameters, antioxidant systems, and activation of MAPK signaling pathways in the copepod Paracyclopina nana.

    Science.gov (United States)

    Kim, Duck-Hyun; Puthumana, Jayesh; Kang, Hye-Min; Lee, Min-Chul; Jeong, Chang-Bum; Han, Jeonghoon; Hwang, Dae-Sik; Kim, Il-Chan; Lee, Jin Wuk; Lee, Jae-Seong

    2016-10-01

    Engineered multi-walled carbon nanotubes (MWCNTs) have received widespread applications in a broad variety of commercial products due to low production cost. Despite their significant commercial applications, CNTs are being discharged to aquatic ecosystem, leading a threat to aquatic life. Thus, we investigated the adverse effect of CNTs on the marine copepod Paracyclopina nana. Additional to the study on the uptake of CNTs and acute toxicity, adverse effects on life parameters (e.g. growth, fecundity, and size) were analyzed in response to various concentrations of CNTs. Also, as a measurement of cellular damage, oxidative stress-related markers were examined in a time-dependent manner. Moreover, activation of redox-sensitive mitogen-activated protein kinase (MAPK) signaling pathways along with the phosphorylation pattern of extracellular signal-regulated kinase (ERK), p38, and c-Jun-N-terminal kinases (JNK) were analyzed to obtain a better understanding of molecular mechanism of oxidative stress-induced toxicity in the copepod P. nana. As a result, significant inhibition on life parameters and evoked antioxidant systems were observed without ROS induction. In addition, CNTs activated MAPK signaling pathway via ERK, suggesting that phosphorylated ERK (p-ERK)-mediated adverse effects are the primary cause of in vitro and in vivo endpoints in response to CNTs exposure. Moreover, ROS-independent activation of MAPK signaling pathway was observed. These findings will provide a better understanding of the mode of action of CNTs on the copepod P. nana at cellular and molecular level and insight on possible ecotoxicological implications in the marine environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Amyloid-β(1–42) Protofibrils Formed in Modified Artificial Cerebrospinal Fluid Bind and Activate Microglia

    Science.gov (United States)

    Paranjape, Geeta S.; Terrill, Shana E.; Gouwens, Lisa K.; Ruck, Benjamin M.; Nichols, Michael R.

    2012-01-01

    Soluble aggregated forms of amyloid-β protein (Aβ) have garnered significant attention recently for their role in Alzheimer’s disease (AD). Protofibrils are a subset of these soluble species and are considered intermediates in the aggregation pathway to mature Aβ fibrils. Biological studies have demonstrated that protofibrils exhibit both toxic and inflammatory activities. It is important in these in vitro studies to prepare protofibrils using solution conditions that are appropriate for cellular studies as well as conducive to biophysical characterization of protofibrils. Here we describe the preparation and characterization of Aβ(1–42) protofibrils in modified artificial cerebrospinal fluid (aCSF) and demonstrate their prominent binding and activation of microglial cells. A simple phosphate/bicarbonate buffer system was prepared that maintained the ionic strength and cell compatibility of F-12 medium but did not contain numerous supplements that interfere with spectroscopic analyses of Aβ protofibrils. Reconstitution of Aβ(1–42) in aCSF and isolation with size exclusion chromatography (SEC) revealed curvilinear β-sheet protofibrils <100 nm in length and hydrodynamic radii of 21 nm. Protofibril concentration determination by BCA assay, which was not possible in F-12 medium, was more accurately measured in aCSF. Protofibrils formed and isolated in aCSF, but not monomers, markedly stimulated TNFα production in BV-2 and primary microglia and bound in significant amounts to microglial membranes. This report demonstrates the suitability of a modified aCSF system for preparing SEC-isolated Aβ(1–42) protofibrils and underscores the unique ability of protofibrils to functionally interact with microglia. PMID:23242692

  4. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats

    Science.gov (United States)

    Kanter, Mehmet; Coskun, Omer; Budancamanak, Mustafa

    2005-01-01

    AIM: To investigate the effects of Nigella sativa L (NS) and Urtica dioica L (UD) on lipid peroxidation, antioxidant enzyme systems and liver enzymes in CCl4-treated rats. METHODS: Fifty-six healthy male Wistar albino rats were used in this study. The rats were randomly allotted into one of the four experimental groups: A (CCl4-only treated), B (CCl4+UD treated), C (CCl4+NS treated) and D (CCl4+UD+NS treated), each containing 14 animals. All groups received CCl4 (0.8 mL/kg of body weight, sc, twice a week for 60 d). In addition, B, C and D groups also received daily i.p. injections of 0.2 mL/kg NS or/and 2 mL/kg UD oils for 60 d. Group A, on the other hand, received only 2 mL/kg normal saline solution for 60 d. Blood samples for the biochemical analysis were taken by cardiac puncture from randomly chosen-seven rats in each treatment group at beginning and on the 60th d of the experiment. RESULTS: The CCl4 treatment for 60 d increased the lipid peroxidation and liver enzymes, and also decreased the antioxidant enzyme levels. NS or UD treatment (alone or combination) for 60 d decreased the elevated lipid peroxidation and liver enzyme levels and also increased the reduced antioxidant enzyme levels. The weight of rats decreased in group A, and increased in groups B, C and D. CONCLUSION: NS and UD decrease the lipid per-oxidation and liver enzymes, and increase the anti-oxidant defense system activity in the CCl4-treated rats. PMID:16425366

  5. Transformation of Astrocytes to a Neuroprotective Phenotype by Microglia via P2Y1 Receptor Downregulation

    Directory of Open Access Journals (Sweden)

    Youichi Shinozaki

    2017-05-01

    Full Text Available Microglia and astrocytes become reactive following traumatic brain injury (TBI. However, the coordination of this reactivity and its relation to pathophysiology are unclear. Here, we show that microglia transform astrocytes into a neuroprotective phenotype via downregulation of the P2Y1 purinergic receptor. TBI initially caused microglial activation in the injury core, followed by reactive astrogliosis in the peri-injured region and formation of a neuroprotective astrocyte scar. Equivalent changes to astrocytes were observed in vitro after injury. This change in astrocyte phenotype resulted from P2Y1 receptor downregulation, mediated by microglia-derived cytokines. In mice, astrocyte-specific P2Y1 receptor overexpression (Astro-P2Y1OE counteracted scar formation, while astrocyte-specific P2Y1 receptor knockdown (Astro-P2Y1KD facilitated scar formation, suggesting critical roles of P2Y1 receptors in the transformation. Astro-P2Y1OE and Astro-P2Y1KD mice showed increased and reduced neuronal damage, respectively. Altogether, our findings indicate that microglia-astrocyte interaction, involving a purinergic signal, is essential for the formation of neuroprotective astrocytes.

  6. Progranulin Is a Chemoattractant for Microglia and Stimulates Their Endocytic Activity

    Science.gov (United States)

    Pickford, Fiona; Marcus, Jacob; Camargo, Luiz Miguel; Xiao, Qiurong; Graham, Danielle; Mo, Jan-Rung; Burkhardt, Matthew; Kulkarni, Vinayak; Crispino, Jamie; Hering, Heike; Hutton, Michael

    2011-01-01

    Mutations resulting in progranulin haploinsufficiency cause disease in patients with a subset of frontotemporal lobar degeneration; however, the biological functions of progranulin in the brain remain unknown. To address this subject, the present study initially assessed changes in gene expression and cytokine secretion in rat primary cortical neurons treated with progranulin. Molecular pathways enriched in the progranulin gene set included cell adhesion and cell motility pathways and pathways involved in growth and development. Secretion of cytokines and several chemokines linked to chemoattraction but not inflammation were also increased from progranulin-treated primary neurons. Therefore, whether progranulin is involved in recruitment of immune cells in the brain was investigated. Localized lentiviral expression of progranulin in C57BL/6 mice resulted in an increase of Iba1-positive microglia around the injection site. Moreover, progranulin alone was sufficient to promote migration of primary mouse microglia in vitro. Primary microglia and C4B8 cells demonstrated more endocytosis of amyloid β1-42 when treated with progranulin. These data demonstrate that progranulin acts as a chemoattractant in the brain to recruit or activate microglia and can increase endocytosis of extracellular peptides such as amyloid β. PMID:21224065

  7. Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP?

    Science.gov (United States)

    Bhandare, Amol M; Kapoor, Komal; Farnham, Melissa M J; Pilowsky, Paul M

    2016-06-01

    Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Presenilin 2 is the predominant γ-secretase in microglia and modulates cytokine release.

    Directory of Open Access Journals (Sweden)

    Suman Jayadev

    2010-12-01

    Full Text Available Presenilin 1 (PS1 and Presenilin 2 (PS2 are the enzymatic component of the γ-secretase complex that cleaves amyloid precursor protein (APP to release amyloid beta (Aβ peptide. PS deficiency in mice results in neuroinflammation and neurodegeneration in the absence of accumulated Aβ. We hypothesize that PS influences neuroinflammation through its γ-secretase action in CNS innate immune cells. We exposed primary murine microglia to a pharmacological γ-secretase inhibitor which resulted in exaggerated release of TNFα and IL-6 in response to lipopolysaccharide. To determine if this response was mediated by PS1, PS2 or both we used shRNA to knockdown each PS in a murine microglia cell line. Knockdown of PS1 did not lead to decreased γ-secretase activity while PS2 knockdown caused markedly decreased γ-secretase activity. Augmented proinflammatory cytokine release was observed after knockdown of PS2 but not PS1. Proinflammatory stimuli increased microglial PS2 gene transcription and protein in vitro. This is the first demonstration that PS2 regulates CNS innate immunity. Taken together, our findings suggest that PS2 is the predominant γ-secretase in microglia and modulates release of proinflammatory cytokines. We propose PS2 may participate in a negative feedback loop regulating inflammatory behavior in microglia.

  9. Population control of resident and immigrant microglia by mitosis and apoptosis.

    Science.gov (United States)

    Wirenfeldt, Martin; Dissing-Olesen, Lasse; Anne Babcock, Alicia; Nielsen, Marianne; Meldgaard, Michael; Zimmer, Jens; Azcoitia, Iñigo; Leslie, Robert Graham Quinton; Dagnaes-Hansen, Frederik; Finsen, Bente

    2007-08-01

    Microglial population expansion occurs in response to neural damage via processes that involve mitosis and immigration of bone marrow-derived cells. However, little is known of the mechanisms that regulate clearance of reactive microglia, when microgliosis diminishes days to weeks later. We have investigated the mechanisms of microglial population control in a well-defined model of reactive microgliosis in the mouse dentate gyrus after perforant pathway axonal lesion. Unbiased stereological methods and flow cytometry demonstrate significant lesion-induced increases in microglial numbers. Reactive microglia often occurred in clusters, some having recently incorporated bromodeoxyuridine, showing that proliferation had occurred. Annexin V labeling and staining for activated caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that apoptotic mechanisms participate in dissolution of the microglial response. Using bone marrow chimeric mice, we found that the lesion-induced proliferative capacity of resident microglia superseded that of immigrant microglia, whereas lesion-induced kinetics of apoptosis were comparable. Microglial numbers and responses were severely reduced in bone marrow chimeric mice. These results broaden our understanding of the microglial response to neural damage by demonstrating that simultaneously occurring mitosis and apoptosis regulate expansion and reduction of both resident and immigrant microglial cell populations.

  10. The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration

    Science.gov (United States)

    Altmann, Christine

    2018-01-01

    Diabetic retinopathy is a common complication of diabetes mellitus, which appears in one third of all diabetic patients and is a prominent cause of vision loss. First discovered as a microvascular disease, intensive research in the field identified inflammation and neurodegeneration to be part of diabetic retinopathy. Microglia, the resident monocytes of the retina, are activated due to a complex interplay between the different cell types of the retina and diverse pathological pathways. The trigger for developing diabetic retinopathy is diabetes-induced hyperglycemia, accompanied by leukostasis and vascular leakages. Transcriptional changes in activated microglia, mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and extracellular signal–regulated kinase (ERK) signaling pathways, results in release of various pro-inflammatory mediators, including cytokines, chemokines, caspases and glutamate. Activated microglia additionally increased proliferation and migration. Among other consequences, these changes in microglia severely affected retinal neurons, causing increased apoptosis and subsequent thinning of the nerve fiber layer, resulting in visual loss. New potential therapeutics need to interfere with these diabetic complications even before changes in the retina are diagnosed, to prevent neuronal apoptosis and blindness in patients. PMID:29301251

  11. Critical Data-Based Re-Evaluation of Minocycline as a Putative Specific Microglia Inhibitor

    NARCIS (Netherlands)

    Moller, Thomas; Bard, Frederique; Bhattacharya, Anindya; Biber, Knut; Campbell, Brian; Dale, Elena; Eder, Claudia; Gan, Li; Garden, Gwenn A.; Hughes, Zoe A.; Pearse, Damien D.; Staal, Roland G. W.; Sayed, Faten A.; Wes, Paul D.; Boddeke, Hendrikus W. G. M.

    2016-01-01

    Minocycline, a second generation broad-spectrum antibiotic, has been frequently postulated to be a "microglia inhibitor." A considerable number of publications have used minocycline as a tool and concluded, after achieving a pharmacological effect, that the effect must be due to "inhibition" of

  12. Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis (Dutch). An immunohistochemical study

    NARCIS (Netherlands)

    Maat-Schieman, M. L.; Rozemuller, A. J.; van Duinen, S. G.; Haan, J.; Eikelenboom, P.; Roos, R. A.

    1994-01-01

    In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) beta/A4 amyloid deposition is found in meningocortical blood vessels and in diffuse plaques in the cerebral cortex. Diffuse plaques putatively represent early stages in the formation of senile plaques. Microglia are intimately

  13. Evidence of Tau Hyperphosphorylation and Dystrophic Microglia in the Common Marmoset.

    Science.gov (United States)

    Rodriguez-Callejas, Juan D; Fuchs, Eberhard; Perez-Cruz, Claudia

    2016-01-01

    Common marmosets ( Callithrix jacchus ) have recently gained popularity in biomedical research as models of aging research. Basically, they confer advantages from other non-human primates due to their shorter lifespan with onset of appearance of aging at 8 years. Old marmosets present some markers linked to neurodegeneration in the brain such as amyloid beta (Aβ) 1-42 and Aβ 1-40 . However, there are no studies exploring other cellular markers associated with neurodegenerative diseases in this non-human primate. Using immunohistochemistry, we analyzed brains of male adolescent, adult, old, and aged marmosets. We observed accumulation of Aβ 1-40 and Aβ 1-42 in the cortex of aged subjects. Tau hyperphosphorylation was already detected in the brain of adolescent animals and increased with aging in a more fibrillary form. Microglia activation was also observed in the aging process, while a dystrophic phenotype accumulates in aged subjects. Interestingly, dystrophic microglia contained hyperphosphorylated tau, but active microglia did not. These results support previous findings regarding microglia dysfunctionality in aging and neurodegenerative diseases as Alzheimer's disease. Further studies should explore the functional consequences of these findings to position this non-human primate as animal model of aging and neurodegeneration.

  14. Microglia protect neurons against ischemia by synthesis of tumor necrosis factor

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Clausen, Bettina Hjelm; Babcock, Alicia

    2009-01-01

    Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical...

  15. Isolation of murine postnatal brain microglia for phenotypic characterization using magnetic cell separation technology.

    Science.gov (United States)

    Harms, Ashley S; Tansey, Malú G

    2013-01-01

    To shorten the time between brain harvesting and microglia isolation, and characterization, we utilized the MACS(®) neural dissociation kit followed by OctoMACS(®) CD11b magnetic bead isolation technique to positively select for brain microglia expressing the pan-microglial marker CD11b, a key subunit of the membrane attack complex (MAC). This protocol yields a viable and highly pure (>95%) microglial population of approximately 500,000 cells per pup that is amenable for in vitro characterization within hours or days after being harvested from brain tissue. Primary microglia from C57Bl/6 mice were plated for next-day analyses of morphology and cellular markers by immunocytochemistry or for analysis of gene expression under resting or LPS-stimulated conditions. The ease of isolation enables investigators to perform molecular and cellular analyses without having to wait 1-2 weeks to isolate microglia by conventional methods involving mechanical agitation to dislodge these from astrocyte beds.

  16. E3 Ubiquitin Ligase c-cbl Inhibits Microglia Activation After Chronic Constriction Injury.

    Science.gov (United States)

    Xue, Pengfei; Liu, Xiaojuan; Shen, Yiming; Ju, Yuanyuan; Lu, Xiongsong; Zhang, Jinlong; Xu, Guanhua; Sun, Yuyu; Chen, Jiajia; Gu, Haiyan; Cui, Zhiming; Bao, Guofeng

    2018-06-22

    E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is associated with negative regulation of receptor tyrosine kinases, signal transduction of antigens and cytokine receptors, and immune response. However, the expression and function of c-cbl in the regulation of neuropathic pain after chronic constriction injury (CCI) are unknown. In rat CCI model, c-cbl inhibited the activation of spinal cord microglia and the release of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), which alleviated mechanical and heat pain through down-regulating extracellular signal-regulated kinase (ERK) pathway. Additionally, exogenous TNF-α inhibited c-cbl protein level vice versa. In the primary microglia transfected with c-cbl siRNA, when treated with TNF-α or TNF-α inhibitor, the corresponding secretion of IL-1β and IL-6 did not