Display omitted
•Treatment with PLX5622 leads to a dose-dependent depletion of microglia.•Treatment with PLX5622 differentially affected cytokines in young and aged mice.•Low doses lead to reduction ...in inflammation circumventing the astrocyte activation.•Depletion of microglia led to decreased expression of the senescence marker p16.•Brain inflammation can be reduced by reducing the microglial cell population.
Chronic macrophage activation was implicated as one of the main culprits for chronical, low-grade inflammation which significantly contributes to development of age-related diseases. Microglia as the brain macrophages have been recently implicated as key players in neuroinflammation and neurodegeneration in the aged brain. Microglial cell functions are indispensable in early development, however, activation or senescence of microglia in aging cells may be detrimental. Depletion of microglia using genetical or pharmacological approaches leads to opposite results regarding effects on brain cognition. In this study we pharmacologically depleted microglia using orally delivered low and high doses of the CSF1R inhibitor PLX5622 and assessed the expression levels of known inflammation markers (TNF-α, IL1-β, IL-6, IL-10), glia markers (Iba-1 and Gfap) and specific senescence marker p16Ink4a in the aged murine brain. Our results indicate that treatment with low and high doses of PLX5622 leads to a dose-dependent depletion of microglial cells with similar levels in young and aged mice. We also show that treatment with low and high PLX5622 differentially affected cytokine levels in young and old brains. By using low doses we could achieve reduction in inflammation circumventing the astrocyte activation. Removal of microglia cells led to decreased expression of the senescence marker p16Ink4a in the aged brain, indicating a relevant contribution of these cells to the expression of this marker and their senescent status in the healthy aging brain. Our results indicate that increased and detrimental brain inflammation in aged murine brain can be impaired by selectively reducing the microglial cell population.
•We determined microglia expression of critical metabolic rate limiting enzymes.•We found different metabolic changes occurring in senescent vs. aged microglia cells.•Senescent microglia display ...glycolysis activation and hypermetabolic state.•Aged microglia are rather in a state of hypometabolism.•Metabolic changes in aged microglia may present a novel therapeutical target.
Microglia, the resident immune cells of the central nervous system, are critically involved in maintaining brain homeostasis. With age, microglia display morphological and functional alterations that have been associated with cognitive decline and neurodegeneration. Although microglia seem to participate in an increasing number of biological processes which require a high energy demand, little is known about their metabolic regulation under physiological and pathophysiological conditions and during aging/senescence. Here, we determined mRNA expression levels of critical rate limiting enzymes in several key metabolic pathways including glycolysis, pentose phosphate pathway, fatty acid oxidation and synthesis in association with oxidative phosphorylation in microglia, both under aging and senescent conditions. We found strong evidence for different metabolic changes occuring in senescent vs. aged microglia cells. While senescent microglia display a hypermetabolic state as indicated by increased expression of key enzymes involved in glycolysis and pentose phosphate pathway, aging microglia are rather in a state of hypometabolism. Our findings indicate that studies involving aging and senescent microglia require a clear differentiation between these microglial states due to profound metabolic differences observed here. Understanding metabolic changes in senescent and aged microglia may lead to novel strategies to decrease over-activation of these cells due to aging, which is associated to the process of inflamm-aging and neurodegeneration.
Microglia, the key innate immune cells in the brain, have been reported to drive brain aging and neurodegenerative disorders; however, few studies have analyzed microglial senescence and the impact ...of aging on the properties of microglia. In the present study, we characterized senescence- and aging-associated phenotypes of murine brain microglia using well-accepted markers, including telomere length, telomerase activity, expression of p16INK4a, p21, p53, senescence-associated β-galactosidase, and a senescence-associated secretory phenotype. Quantitative real-time polymerase chain reaction analysis and a Telomeric Repeat Amplification Protocol assay indicated shortened telomeres and increased telomerase activity in senescent microglia, whereas telomeres remained unaltered and telomerase activity was reduced in aged microglia. Senescent microglia upregulated p16INK4a, p21, and p53, whereas acutely isolated microglia from the aged brain only exhibited a modest upregulation of p16INK4a. Senescent microglia showed decreased proliferation, while it was unchanged in aged microglia. Furthermore, microglia at late passages strongly upregulated expression of the senescent marker senescence-associated β-galactosidase. Senescent and aged microglia exhibited differential activation profiles and altered responses to stimulation. We conclude that microglia from the aged mouse brain do not show typical senescent changes because their phenotype and functional response strongly differ from those of senescent microglia in vitro.
•A comparative analysis of senescent and aged microglia was performed.•Microglia exhibited typical senescence markers after long-term culture.•Aged microglia expressed p16 and showed a different activation profile.•Both, young and aged microglia show increased p16 expression.•We show that microglia from the aged brain are dysfunctional but not senescent.
Based on investigations of ash deposit formation, semi-empirical indicators for slagging and fouling, based on ash chemical composition and its fusion temperature, have been determined. These ...criteria-indicators, in suggested limits, describe the coals on which they are based (North-American and British) well. However, the experience in the thermal power production sector of Serbia shows that their literal application to domestic coals does not produce satisfactory results. This contribution provides an analysis of applicability and the choice of criteria that are suitable for Serbian coals. The focus of the contribution is on coal slagging indicators, since slagging has much heavier consequences on heat transfer inside the steam boiler, and on boiler operation as a whole. The basis for the analysis of chosen criteria comprises of the results of investigations of four coal fields - Kostolac, Kolubara, Kosovo (Serbia), and Ugljevik (Bosnia and Herzegovina).
nema
The aim of the investigation was to make some reconstructions on the existing stove used for cooking and baking and to obtain the combined cooker-boiler which will fulfill the demands of European ...standard EN 12815. Implementation of modern scientific achievements in the field of combustion on stoves and furnaces fired on biomass was used. During the investigations four various constructions were made with different fresh air inlet and secondary air supply with the intention to obtain more complete combustion with increased efficiency and reduced CO emission. Three different fuels were used: firewood, coal, and wood briquette. A numerous parameters were measured: fuel weight changes during the combustion process, temperature of inlet and outlet water, flue gas composition (02, CO, SO2, CO2, NO'), flue gas temperature, ash quantity ect. The result of the investigations is the stove with the efficiency of more than 75% - boiler Class 1 (according EN 12815) and CO emission of about 1 %v/v. The results obtained during the measurements were used as parameters for modeling of combustion process.
Memantine is the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, used in the treatment of Alzheimer's disease. It is also known that memantine pretreatment assured protection of ...skeletal muscles from poisoning with nerve agents and an interaction between memantine and AChE was proposed. In the study presented we examined interactions of memantine and its main metabolite (1-amino-3-hydroxymethyl-5-methyl adamantine, Mrz 2/373) with AChE in vitro as well as their effect on kinetics of the soman-induced AChE inhibition and aging. The results have shown that memantine and Mrz 2/373 exerted concentration-dependent inhibition of AChE, with Mrz 2/373 being a more potent inhibitor than the parent compound. Addition of soman 7.5 nmol/l induced gradual AChE inhibition that became almost complete after 20 min. Memantine (0.1, 0.5 and 1 mmol/l) and Mrz 2/373 (0.1, 0.5 and 1 mmol/l) concentration-dependently slowed down the AChE inhibition. After 30 min of incubation of AChE with soman, 5 min of aging and 20 min of reactivation by asoxime (HI-6 dichloride), AChE activity was 8.1% in control medium, 30.7% and 41.9% after addition of 1 and 10 mmol/l memantine, and 16.1% after addition of 1 mmol/l Mrz 2/373. It was concluded that it is possible that memantine and Mrz 2/373 can prevent AChE from inhibition by soman, which could, along with known memantine's neuroprotective activity, explain its potent antidotal effect in soman poisoning. The potential effect on aging of the soman-AChE complex warrants further studies.
•Memantine and its metabolite Mrz 2/373 inhibit bovine acetylcholinesterase in vitro.•Both these adamantanes slow-down inhibition of acetylcholinesterase caused by soman.•They enable better reactivation by HI-6 of acetylcholinesterase inhibited by soman.•They might decrease the aging rate of the soman-acetylcholinesterase complex.•These effects of adamantanes are obtained by using their millimolar concentrations.
The aim of the investigation was to make some reconstructions on the existing stove used for cooking and baking and to obtain the combined cooker-boiler which will fulfill the demands of European ...standard EN 12815. Implementation of modern scientific achievements in the field of combustion on stoves and furnaces fired on solid fuels was used. During the investigations four various constructions were made with different fresh air inlet and secondary air supply with the intention to obtain more complete combustion with increased efficiency and reduced CO emission. Three different fuels were used: firewood, coal, and wood briquette. A numerous parameters were measured: fuel weight changes during the combustion process, temperature of inlet and outlet water, flue gas composition (O2, CO, SO2, CO2, NOx), flue gas temperature, ash quantity etc. The result of the investigations is the stove with the efficiency of more than 75% - boiler Class 1 (according EN 12815) and CO emission of about 1% v/v. The results obtained during the measurements were used as parameters for modeling of combustion process. .
This paper presents the influence of varieties and different doses of applied
nitrogen on grain yield and protein content of triticale. The experiment was
set in the period from 2010 to 2012 in the ...north of Montenegro, in the
vicinity of Bijelo Polje. The research included 5 varieties of winter
triticale (Odyssey, Kg-20, Triumph, Rtanj and Tango) originating from
different breeding houses and the following varieties of fertilization:
control (without fertilization), only nitrogen in the amount of 60 kg ha-1
and nitrogen in the amount of 60 and 90 kg ha-1 in combination with the same
amount of phosphorus and potassium (80 kg ha-1). The results of the study
showed that the lowest average grain yield was obtained in the
non-fertilizing variant - control. The use of fertilizers in all tested
varieties has led to a very significant increase in yield in all variants
compared to control. The Kg-20 variety had the lowest average yield, and the
Tango variety had the highest. The highest average protein content was
achieved in the fertilizer variant where only nitrogen was used in the
amount of 60 kg ha-1. Among the researched varieties, the Triumph variety
had the highest protein content in the grains. The data on the achieved
yields and the content of protein in grains, depending on the variety and
the used doses of fertilizer, indicate the characteristics of individual
varieties and can serve as a criterion for the selection of the most
suitable variety for certain agroecological conditions. This is particularly
important for cattle-oriented farms, where the main priority is to ensure a
sufficient amount of quality food.
nema
The goal of this paper was to determine the yield of different maize hybrids
depending on soil type and compaction. The experiment was carried out in
2016 and 2017 on the territory of the Leskovac ...municipality, including three
different soil types (alluvium, vertisol, and parapodzol). The experiment
comprised nine hybrids of different FAO maturity groups (NS 4051, AGR DIAN,
ZP 427, NS 5211, ZP 555, AS 534, NS 6030, ZP 666 and Becar). The highest
average yields were achieved on alluvium, then on parapodzol, and the lowest
yields were obtained on vertisol. The highest average yields on all examined
soil types were achieved in the FAO 500 maturity group, and the lowest in
the FAO 400 maturity group. The highest average yield on vertisol was
achieved in the FAO 500 maturity group, on parapodzol in the FAO 400
maturity group, and on alluvium in the FAO 600 maturity group. The highest
average yield (11.90 t ha-1) was achieved with the ZP 666 hybrid on
alluvium, and the lowest (4.60 t ha-1) with the NS 6030 hybrid on vertisol.
The largest soil compaction in the ploughing layer was determined in
vertisol, then in parapodzol, and the smallest in alluvium. These data on
average yields indicate the convenience of certain soil types for maize
production, and provide guidelines for growers to select the most yielding
hybrids for their fields.
nema
This study was aimed to investigate the possibility of modifying the rate of aging of diisopropylfluorophosphate-inhibited neuropathy target esterase (NTE) of hen brain. This reaction on NTE occurs ...with a half-time of 7.4 min. Atropine was effective in decreasing the rate of aging on DFP-inhibited NTE and this effect was time- and concentration-dependent. Atropine was also a weak but progressive inhibitor of NTE activity (I
50=80 mM) and this reaction appears to be reversible at lower atropine concentrations. Among compounds containing oxime functional groups only OPAB, having longer methylene chain and being more lipophylic than other oximes usually used in acetylcholinesterase (AChE) reactivation studies, was effective in decreasing the rate of aging on DFP-inhibited NTE. However, when atropine and oximes were used together we have obtained a potentiating and/or synergistic effect which was most significant with combination of atropine and TMB-4 giving up to a 15-fold decrease in the rate of aging reaction. The efficacy of this particular combination was concentration-dependent. We have also discussed similarities and differences in aging reaction occurring on NTE and AChE.
PDF
