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1.
Data Brief ; 53: 110242, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38533120

RESUMO

Particulate matter (PM) present in the air pollution increases morbidity and mortality due to several reasons. The dataset presents a comparative analysis of nebulization process of Fe2O3 and SiO2 nanoparticles or crude PM (NIST1648a) and that with reduced content of organic matter (LAp120). Nebulization tests were carried out to determine concentrations of nanoparticle and PM suspensions, in order to create an atmosphere with a concentration of PM particles about 1000 µg/m3 of air in the exposure chambers. It is important to properly recreate environmental conditions during further research on animals. The absorbance spectrum of the suspensions of the tested materials was measured in the range of 300-700 nm. The changes in the absorbance of these suspensions depending on the concentration after their passage through the nebulizers were examined. Based on the absorbance, it was determined to what extent the suspensions are passed out and dispersed by the nebulizers. The operating mode of the nebulizers and the concentration of suspensions were determined in order to establish the optimal exposure conditions and the microclimate of the chambers for further studies with mice. The dataset can help in optimization of nebulization process for all researchers exploring the further issue of the influence of the air pollution on the broadly understood animal functions, behavioral parameters and biochemical aspects.

2.
Pharmacol Rep ; 75(6): 1474-1487, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37725330

RESUMO

BACKGROUND: Parkinson's disease (PD) is a motor disorder characterized by the degeneration of dopaminergic neurons, putatively due to the accumulation of α-synuclein (α-syn) in Lewy bodies (LBs) in Substantia Nigra. PD is also associated with the formation of LBs in brain areas responsible for emotional and cognitive regulation such as the amygdala and prefrontal cortex, and concurrent depression prevalence in PD patients. The exact link between dopaminergic cell loss, α-syn aggregation, depression, and stress, a major depression risk factor, is unclear. Therefore, we aimed to explore the interplay between sensitivity to chronic stress and α-syn aggregation. METHODS: Bilateral injections of α-syn preformed fibrils (PFFs) into the striatum of C57Bl/6 J mice were used to induce α-syn aggregation. Three months after injections, animals were exposed to chronic social defeat stress. RESULTS: α-syn aggregation did not affect stress susceptibility but independently caused increased locomotor activity in the open field test, reduced anxiety in the light-dark box test, and increased active time in the tail suspension test. Ex vivo analysis revealed modest dopaminergic neuron loss in the substantia nigra and reduced dopaminergic innervation in the dorsal striatum in PFFs injected groups. α-Syn aggregates were prominent in the amygdala, prefrontal cortex, and substantia nigra, with minimal α-syn aggregation in the raphe nuclei and locus coeruleus. CONCLUSIONS: Progressive bilateral α-syn aggregation might lead to compensatory activity increase and alterations in emotionally regulated behavior, without affecting stress susceptibility. Understanding how α-syn aggregation and degeneration in specific brain structures contribute to depression and anxiety in PD patients requires further investigation.


Assuntos
Doença de Parkinson , Animais , Humanos , Camundongos , alfa-Sinucleína/metabolismo , Encéfalo/metabolismo , Corpo Estriado/metabolismo , Neurônios Dopaminérgicos/metabolismo , Substância Negra/metabolismo
3.
Sci Rep ; 12(1): 19015, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348016

RESUMO

Eleven multiple analogs of bradykinin-a peptide that is a natural ligand of B1 and B2 receptors but does not bind or activate the B1 receptor unless Arg9 is removed from the sequence by the action of carboxypeptidase N-were synthesized. Their biological activity was examined on T-REx cell lines expressing B1 or B2 receptors using the intracellular IP1 assay. The mRNA expression of B1R and B2R in the lysate of tumor cell lines, e.g., U87-MG (human astrocytoma), SHP-77 (human small cell lung cancer), and H4 (human brain glioma), was determined. For five B1R antagonists, adsorption at the liquid/solid interface (Au nanoparticles (AuNPs) served as the solid surface) was discussed in terms of the vibrations of molecular fragments (structural factors) responsible for the biological properties of these analogs.


Assuntos
Bradicinina , Nanopartículas Metálicas , Humanos , Receptor B1 da Bradicinina/genética , Receptor B2 da Bradicinina/genética , Ouro , Fatores de Transcrição
4.
Animals (Basel) ; 12(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36290158

RESUMO

The composition of the diet, including the amount and type of lipid supplements, influences the products formed in the digestive tract, their levels in the blood and their deposition in the tissues. One example of a plant rich in polyunsaturated fatty acids is flax (Linum usitatissimum). The aim of the presented work was to evaluate the effect of the linseed oil ethyl esters additive and environmental conditions on the selected rabbit blood parameters. The study included two types of animal maintenance (laboratory conditions and external conditions) and two seasons (summer and winter), a total of four study stages. At each stage, a control group and an experimental group were specified. The feed supplement in the form of esterified linseed oil was administered to the experimental animals for two months. The blood samples were collected at the beginning of the experiment, as well as at the end of treatment. Moreover, blood samples were collected also after two months from the end of the experiment. During the experiment, morphological and biochemical parameters of the rabbits' blood were examined. The results of the content of fatty acids were determined in the erythrocytes and serum blood samples and grouped into saturated and unsaturated fatty acids, especially omega-3 and omega-6 fatty acids. In an internal study, the influence of housing conditions and season on selected morphological and biochemical parameters of rabbit blood was confirmed. Furthermore, expected beneficial changes in the fatty acid profile in erythrocytes and blood serum were observed as a result of supplementation. A significant increase in omega-3 fatty acids was noted as well as a substantial decrease in the ratio of omega-6 to omega-3 fatty acids (p < 0.01). Most importantly, the linseed oil ethyl ester supplement used did not adversely affect the health of the rabbits, as evidenced by biochemical and blood morphological indices remaining within, known so far, reference limits or showing only slight fluctuations (p > 0.05). However, the obtained results extend the database of hematological blood parameters in rabbits, thus, contributing to improvements in laboratory diagnostics for fur animals.

5.
Biomolecules ; 12(8)2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-36008994

RESUMO

Despite the variable chemical and physical characteristics of particulate air pollutants, inflammation and oxidative stress have been identified as common mechanisms for cell damage and negative health influences. These effects are produced by organic components, especially by endotoxins. This study analyzed the gene expression profile after exposure of RAW 264.7 cells to the standard particulate matter (PM) material, NIST1648a, and PM with a reduced organic matter content, LAp120, in comparison to the effects of lipopolysaccharide (LPS). The selected parameters of cell viability, cell cycle progression, and metabolic and inflammatory activity were also investigated. Both forms of PM negatively influenced the parameters of cell activity. These results were generally reflected in the gene expression profile. Only NIST1648a, excluding LAp120, contained endotoxins and showed small but statistically significant pro-inflammatory activity. However, the gene expression profiling revealed strong pro-inflammatory cell activation induced by NIST1648a that was close to the effects of LPS. Changes in gene expression triggered by LAp120 were relatively small. The observed differences in the effects of NIST1648a and LAp120 were related to the content of organic matter in which bacterial endotoxins play an important role. However, other organic compounds and their interactions with other PM components also appear to be of significant importance.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/toxicidade , Endotoxinas/análise , Endotoxinas/toxicidade , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Material Particulado/toxicidade , Transcriptoma
6.
Animals (Basel) ; 12(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35454218

RESUMO

The aim of the study was to show the impact of environmental conditions and dietary supplementation with ethyl esters of linseed oil on the quality of the rabbit hair coat. The research was divided into 4 stages: laboratory (summer and winter) and outdoor (summer and winter). In each stage of the research, animals were divided into control and experimental groups. The animals were fed in accordance with the feeding standards of reproductive rabbits during the period of sexual dormancy. The rabbits from the experimental groups during the first two months were given an addition of ethyl linseed oil to the feed. In the experiment, linseed oil was cold-pressed directly in the laboratory. Three samples of hair were collected: before the study, after two months of treatment, and after two months from the end of supplementation. The hair coat biological properties, such as share of individual hair fractions (%), heat transfer index (HTI), hair diameter (µm), as well as physico-mechanical properties such as breaking force (N), breaking stress (kg/cm2) and elongation (%) were performed. Moreover, the histological structure of hair and histological hair evaluation were performed. The fatty acid profile was determined in the hair as well. The obtained results of the content of individual fatty acids were grouped into saturated fatty acids and unsaturated fatty acids. In addition, omega-3 and omega-6 were distinguished from the group of unsaturated acids. The environmental conditions have a major impact on the quality of the rabbit coat. The best results of hair thickness and their heat protection were obtained from animals kept outdoors. The studies did not show an influence of the administered preparation on the quality of the rabbit coat. The hair became thinner, but more flexible and tear-resistant. Administration of linseed oil ethyl esters had significant, beneficial changes in the fatty acid profile in hair and hair sebum were observed. There was a significant increase in omega-3 acids, and a significant decrease in the ratio of omega-6 to omega-3 acids.

7.
Toxics ; 9(9)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34564356

RESUMO

Exposure to air pollution from various airborne particulate matter (PM) is regarded as a potential health risk. Airborne PM penetrates the lungs, where it is taken up by macrophages, what results in macrophage activation and can potentially lead to negative consequences for the organism. In the present study, we assessed the effects of direct exposure of RAW 264.7 macrophages to crude PM (NIST1648a) and to a reduced content of organic matter (LAp120) for up to 72 h on selected parameters of metabolic activity. These included cell viability and apoptosis, metabolic activity and cell number, ROS synthesis, nitric oxide (NO) release, and oxidative burst. The results indicated that both NIST1648a and LAp120 negatively influenced the parameters of cell viability and metabolic activity due to increased ROS synthesis. The negative effect of PM was concentration-dependent; i.e., it was the most pronounced for the highest concentration applied. The impact of PM also depended on the time of exposure, so at respective time points, PM induced different effects. There were also differences in the impact of NIST1648a and LAp120 on almost all parameters tested. The negative effect of LAp120 was more pronounced, what appeared to be associated with an increased content of metals.

8.
Front Cell Neurosci ; 15: 647643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248501

RESUMO

Air pollution is regarded as an important risk factor for many diseases that affect a large proportion of the human population. To date, accumulating reports have noted that particulate matter (PM) is closely associated with the course of cardiopulmonary disorders. As the incidence of Alzheimer's disease (AD), Parkinson's disease (PD), and autoimmune disorders have risen and as the world's population is aging, there is an increasing interest in environmental health hazards, mainly air pollution, which has been slightly overlooked as one of many plausible detrimental stimuli contributing to neurodegenerative disease onset and progression. Epidemiological studies have indicated a noticeable association between exposure to PM and neurotoxicity, which has been gradually confirmed by in vivo and in vitro studies. After entering the body directly through the olfactory epithelium or indirectly by passing through the respiratory system into the circulatory system, air pollutants are subsequently able to reach the brain. Among the potential mechanisms underlying particle-induced detrimental effects in the periphery and the central nervous system (CNS), increased oxidative stress, inflammation, mitochondrial dysfunction, microglial activation, disturbance of protein homeostasis, and ultimately, neuronal death are often postulated and concomitantly coincide with the main pathomechanisms of neurodegenerative processes. Other complementary mechanisms by which PM could mediate neurotoxicity and contribute to neurodegeneration remain unconfirmed. Furthermore, the question of how strong and proven air pollutants are as substantial adverse factors for neurodegenerative disease etiologies remains unsolved. This review highlights research advances regarding the issue of PM with an emphasis on neurodegeneration markers, symptoms, and mechanisms by which air pollutants could mediate damage in the CNS. Poor air quality and insufficient knowledge regarding its toxicity justify conducting scientific investigations to understand the biological impact of PM in the context of various types of neurodegeneration.

9.
Viruses ; 13(7)2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201873

RESUMO

The aim of this study was the isolation and characterization, including the phage effect on honeybees in laboratory conditions, of phages active against Paenibacillus larvae, the causative agent of American Foulbrood-a highly infective and easily spreading disease occurring in honeybee larva, and subsequently the development of a preparation to prevent and treat this dangerous disease. From the tested material (over 2500 samples) 35 Paenibacillus spp. strains were obtained and used to search for phages. Five phages specific to Paenibacillus were isolated and characterized (ultrastructure, morphology, biological properties, storage stability, and genome sequence). The characteristics were performed to obtain knowledge of their lytic potential and compose the final phage cocktail with high antibacterial potential and intended use of future field application. Preliminary safety studies have also been carried out on healthy bees, which suggest that the phage preparation administered is harmless.


Assuntos
Bacteriófagos/isolamento & purificação , Bacteriófagos/fisiologia , Abelhas/microbiologia , Paenibacillus larvae/virologia , Animais , Bacteriólise , Bacteriófagos/ultraestrutura , Endotoxinas/metabolismo , Especificidade de Hospedeiro , Paenibacillus larvae/metabolismo , Polônia
10.
PLoS One ; 16(6): e0252858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34166412

RESUMO

The amount of artificial electromagnetic fields of various parameters in the honey bee's environment increases globally. So far, it had been proven that exposure to an E-field at 50 Hz can cause changes in bee's behavior, alter the activity of proteases, and enzymatic antioxidants. Due to the potentially harmful effect of this factor on honey bees, we decided to investigate the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), and the concentration of albumin and creatinine in bee's hemolymph after exposure to 50 Hz E-field. Honey bee workers were placed in wooden cages (200 × 150 × 70 mm) and exposed to the 50 Hz E-field with the intensity of <1, 5.0, 11.5, 23.0, or 34.5 kV/m for 1, 3, 6, or 12h. A homogeneous 50 Hz E-field was generated in the form of a plate capacitor. Hemolymph samples for analysis were taken immediately after the end of exposure to the E-field from 100 bees from each group. According to our study, the activity of AST, ALT, and ALP in honey bees' hemolymph decreased after exposure to 50 Hz E-field with various intensities. The decrease in AST, ALT, and ALP activity intensified with prolonged exposure time. 50 Hz E-field may cause the impairment of crucial metabolic cycles in the honey bees' organism (such as the citric acid cycle, ATP synthesis, oxidative phosphorylation, ß-oxidation). Moreover, exposure to E-Field altered the concentration of creatinine and albumin, which are important non-enzymatic antioxidants. Such changes may indicate a disturbance in protein metabolism and increased muscle activity.


Assuntos
Abelhas/metabolismo , Biomarcadores/metabolismo , Eletricidade/efeitos adversos , Hemolinfa/metabolismo , Proteínas de Insetos/metabolismo , Animais , Abelhas/efeitos dos fármacos , Hemolinfa/efeitos dos fármacos
11.
Animals (Basel) ; 11(3)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803600

RESUMO

The effect of an artificial electromagnetic field on organisms is a subject of extensive public debate and growing numbers of studies. Our study aimed to show the effect of an electromagnetic field at 50 Hz and variable intensities on honey bee proteolytic systems and behavior parameters after 12 h of exposure. Newly emerged worker bees were put into cages and exposed to a 50 Hz E-field with an intensity of 5.0 kV/m, 11.5 kV/m, 23.0 kV/m, or 34.5 kV/m. After 12 h of exposure, hemolymph samples were taken for protease analysis, and the bees were recorded for behavioral analysis. Six behaviors were chosen for observation: walking, flying, self-grooming, contact between individuals, stillness, and wing movement. Bees in the control group demonstrated the highest number of all behavior occurrences, except flying, and had the lowest protease activity. Bees in the experimental groups showed a lower number of occurrences of walking, self-grooming, and contacts between individuals than the control bees and had significantly higher protease activity than the control bees (except that of alkaline proteases in the 23.0 kV/m group).

12.
Animals (Basel) ; 11(2)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498413

RESUMO

EM-fields come from both natural and anthropogenic sources. This study aimed to investigate changes in honeybee behavior parameters under the influence of an electric field at 50 Hz and variable intensity. Bees were exposed for 1 h, 3 h, or 6 h to the following artificial E-field intensities: 5.0 kV/m, 11.5 kV/m, 23.0 kV/m, or 34.5 kV/m. Bees in the control group were under the influence of an E-field <2.0 kV/m. Six basic behaviors were selected for bee observation (walking, grooming, flight, stillness, contact between individuals, and wing movement). Our research shows the impact of bee exposure time on behavioral change within groups. Exposure for 3 h caused a decrease in the time that bees spent on behaviors and in the number of occurrences. After 6 h, the parameters increased within the groups, as was the case with 1 h exposure. This may indicate that there is a behavioral barrier that allows the pattern to normalize for some time.

13.
Insects ; 11(10)2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33081029

RESUMO

In recent years, on a global scale, more and more reports of a phenomenon called CCD (Colony Collapse Disorder) have been reported. In addition to pesticides, diseases, and other environmental stressors, electromagnetic fields are also mentioned as one of the possible causes of CCD. One of the body's first lines of defense against harmful factors is the antioxidant system. We hypothesized that electromagnetic field upregulate the activity of SOD (superoxide dismutase), CAT (catalases), and changed FRAP (total antioxidant potential) in honeybee hemolymph. In our research, 12 h bee's exposure to E-field was analyzed to determine changes in the antioxidant system. The frequency of 50 Hz and various intensities were used: 5.0 kV/m, 11.5 kV/m, 23.0 kV/m, and 34.5 kV/m. Superoxide dismutase was characterized by four times higher activity in the study groups as compared to the control group. Catalase activity in all groups was characterized by statistically significantly different activity between the groups. The highest activity was recorded in the 34.5 kV/m group. The lowest activity was recorded in the 11.5 kV/m group. A relationship was found between different E-field intensities and changes in the antioxidant system.

14.
Front Microbiol ; 11: 1913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849478

RESUMO

American foulbrood is one of the most serious and yet unsolved problems of beekeeping around the world, because it causes a disease leading to the weakening of the vitality of honey bee populations and huge economic losses both in agriculture and horticulture. The etiological agent of this dangerous disease is an extremely pathogenic spore-forming bacterium, Paenibacillus larvae, which makes treatment very difficult. What is more, the use of antibiotics in the European Union is forbidden due to restrictions related to the prevention of the presence of antibiotic residues in honey, as well as the global problem of spreading antibiotic resistance in case of bacterial strains. The only available solution is burning of entire bee colonies, which results in large economic losses. Therefore, bacteriophages and their lytic enzymes can be a real effective alternative in the treatment and prevention of this Apis mellifera disease. In this review, we summarize phage characteristics that make them a potentially useful tool in the fight against American foulbrood. In addition, we gathered data regarding phage application that have been described so far, and attempted to show practical implications and possible limitations of their usage.

15.
Nucleic Acids Res ; 48(16): 9007-9018, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32710625

RESUMO

In most animals, the start of embryogenesis requires specific histones. In Drosophila linker histone variant BigH1 is present in early embryos. To uncover the specific role of this alternative linker histone at early embryogenesis, we established fly lines in which domains of BigH1 have been replaced partially or completely with that of H1. Analysis of the resulting Drosophila lines revealed that at normal temperature somatic H1 can substitute the alternative linker histone, but at low temperature the globular and C-terminal domains of BigH1 are essential for embryogenesis. In the presence of BigH1 nucleosome stability increases and core histone incorporation into nucleosomes is more rapid, while nucleosome spacing is unchanged. Chromatin formation in the presence of BigH1 permits the fast-paced nuclear divisions of the early embryo. We propose a model which explains how this specific linker histone ensures the rapid nucleosome reassembly required during quick replication cycles at the start of embryogenesis.


Assuntos
Divisão do Núcleo Celular , Cromatina/metabolismo , Proteínas de Drosophila/fisiologia , Drosophila/embriologia , Histonas/metabolismo , Nucleossomos/metabolismo , Animais , Montagem e Desmontagem da Cromatina , Embrião não Mamífero , Desenvolvimento Embrionário , Histonas/fisiologia
16.
Animals (Basel) ; 9(10)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31601049

RESUMO

The study evaluated the anti-colibacteriosis efficacy of herbs in experimental infection by rabbit pathogenic strain of E. coli O103 eae+. It also studied the effects of herbal mixture added to feed or water on blood parameters. This animal model was used since some E. coli strains pathogenic for rabbits are similar to the strains that are pathogenic to humans. The components of herbal extracts were Rumex crispus, Pontentilla anserine, and Polygonum aviculare. Supplementation was carried out in water (ExpW group) or feed (ExpF group), and four weeks later the animals were infected with the E. coli O103 eae+ strain. The administration of herbs increased the mean concentration of total protein and serum albumin (p < 0.01) without causing disturbances of electrolyte and acid-base balance. The highest total antioxidant capacity (TAS) value (p < 0.01) was observed in the ExpF group. The administration of a mixture of herbs and feed caused more reduction in the number of E. coli in cecum than supplementation into water after an experimental infection. The herbs applied in rabbits did not harm the secretory functions of liver, electrolyte, and acid-base balance of the blood. The application of the tested herbal mixtures can control the activity of the intestinal microbial community.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30953677

RESUMO

Disturbances in fear-evoked signal transduction in the hippocampus (HP), the nuclei of the amygdala (AMY), and the prefrontal cortex (PFC) underlie anxiety-related disorders. However, the molecular mechanisms underlying these effects remain elusive. Heterotrimeric G proteins (GPs) are divided into the following four families based on the intracellular activity of their alpha subunit (Gα): Gα(s) proteins stimulate cyclic AMP (cAMP) generation, Gα(i/o) proteins inhibit the cAMP pathway, Gα(q/11) proteins increase the intracellular Ca++ concentration and the inositol trisphosphate level, and Gα(12/13) proteins activate monomeric GP-Rho. In the present study, we assessed the effects of a fear memory procedure on the mRNA expression of the Gα subunits of all four GP families in the HP, AMY and PFC. C57BL/6 J mice were subjected to a fear conditioning (FC) procedure followed by a contextual or cued fear memory test (CTX-R and CS-R, respectively). Morphine (MOR, 1 mg/kg/ip) was injected immediately after FC to prevent the fear consolidation process. Real-time quantitative PCR was used to measure the mRNA expression levels of Gα subunits at 1 h after FC, 24 h after FC, and 1 h after the CTX-R or CS-R. In the HP, the mRNA levels of Gα(s), Gα(12) and Gα(11) were higher at 1 h after training. Gα(s) levels were slightly lower when consolidation was stabilized and after the CS-R. The mRNA levels of Gα(12) were increased at 1 h after FC, returned to control levels at 24 h after FC and increased again with the CTX-R. The increase in the Gα(11) level persisted at 24 h after FC and after CTX-R. In the AMY, no specific changes were induced by FC. In the PFC, CTX-R was accompanied by a decrease in Gα(i/o) mRNA levels; however, only Gα(i2) downregulation was prevented by MOR treatment. Hence, the FC-evoked changes in Gα mRNA expression were observed mainly in the HP and connected primarily to contextual learning. These results suggest that the activation of signaling pathways by Gα(s) and Gα(12) is required to begin the fear memory consolidation process in the HP, while signal transduction via Gα(11) is implicated in the maintenance of fear consolidation. In the PFC, the downregulation of Gα(i2) appears to be related to the contextual learning of fear.


Assuntos
Encéfalo/metabolismo , Medo , Proteínas de Ligação ao GTP/metabolismo , Memória/efeitos dos fármacos , Morfina/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Sinais (Psicologia) , Medo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo
18.
Immunobiology ; 223(2): 227-238, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29030008

RESUMO

Disturbances in brain monoamines, overactivity of the hypothalamo-pituitary adrenal (HPA) axis and pro-inflammatory tendency in the immune system are the key features of depressive disorders. Recently, several murine lines with mutations in glucocorticoid receptors (GRs) have been generated and these animals may be utilized for study depressive-like disorders. In the present study, we have investigated whether selective ablation of GRs in noradrenergic neurons affects functional properties of leukocytes and redirects them towards pro-inflammatory activity. Transgenic mice selectively devoid of GRs on noradrenergic cells were constructed using the Cre/loxP approach. Peritoneal leukocytes were collected from mutant and wild type (WT) animals of both sexes and were cultured in vitro for 24h both in basal conditions and after application of selected pro- or anti-inflammatory stimuli. Metabolic activity and adherence were measured in basal conditions. Nitric oxide (NO) synthesis and arginase (ARG) activity were assessed as the markers of functional status of the cells. Because adult mutant mice lack adrenal medulla and thereby peripheral adrenaline, we modulated pro- and anti-inflammatory culture conditions by addition of noradrenaline (10-6M). Finally, effects of in vivo pro-inflammatory challenge (with intraperitoneal administration of lipopolysaccharide) on properties of leukocytes were assessed 24h (in both sexes) and 48h later (in males only). The experiments indicated that selective ablation of GR in noradrenergic neurons did not affect fundamental properties of peritoneal leukocytes and exerted effects only under conditions of selected pro- or anti-inflammatory stimuli in vitro. Stronger response to pro-inflammatory stimulation in terms of NO synthesis and ARG activity may suggest pro-inflammatory tendency in mutant mice. In vivo inflammatory challenge failed to show any effect of GR ablation on selected parameters of leukocyte activity. Both in vitro studies and in vivo challenge revealed mainly sex-related differences in leukocyte activity.


Assuntos
Neurônios Adrenérgicos/fisiologia , Transtorno Depressivo/imunologia , Leucócitos/imunologia , Peritônio/imunologia , Receptores de Glucocorticoides/genética , Animais , Arginase/metabolismo , Células Cultivadas , Transtorno Depressivo/genética , Feminino , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/metabolismo
19.
Prog Neuropsychopharmacol Biol Psychiatry ; 80(Pt C): 279-290, 2018 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-28433460

RESUMO

The effect of antidepressant drugs on tumor progress is very poorly recognized. The aim of the present study was to examine the effect of individual reactivity to stress and 24-day desipramine (DES) administration on the metastatic colonization of adenocarcinoma MADB 106 cells in the lungs of Wistar rats. Wistar rats were subjected to stress procedure according to the chronic mild stress (CMS) model of depression for two weeks and stress highly-sensitive (SHS) and stress non-reactive (SNR) rats were selected. SHS rats were more prone to cancer metastasis than SNR ones and chronic DES treatment further increased the number of lung metastases by 59% and 50% in comparison to vehicle-treated appropriate control rats. The increase in lung metastases was connected with DES-induced skew macrophage activity towards M2 functional phenotype in SHS and SNR rats. Moreover, during 24h after DES injection in healthy rats, the decreased number of TCD8+ and B cells in SHS and SNR rats as well as NK cell cytotoxic activity in SNR rats could be attributed to the lowered capacity to defend against cancer metastasis observed in chronic DES treated and tumor injected rats.


Assuntos
Adenocarcinoma/complicações , Adenocarcinoma/secundário , Desipramina/farmacologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/secundário , Estresse Psicológico/complicações , Animais , Antidepressivos/farmacologia , Linhagem Celular Tumoral , Subpopulações de Linfócitos/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos
20.
Int Immunopharmacol ; 48: 35-42, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28460354

RESUMO

Some antidepressants show a significantly lower efficacy in elderly patients, particularly in women. Previous studies have shown that antidepressants administered to young animals reduced depression-like symptoms induced by lipopolysaccharide (LPS). The aim of this study was to find out whether the antidepressant and anti-inflammatory properties of fluoxetine (FLU) can be observed also in old female C57BL/6J mice. A depression-like state was evoked by the administration of LPS (100µg/kg for 4 consecutive days) which was followed by reduction of sucrose preference (anhedonia) and enhancement of immobility-time in the forced swim test (FST). Animals, which received FLU (10mg/kg, 11days) exhibited a decreased LPS-induced expression of some inflammatory cytokines in the hippocampus and spleen but this effect was not accompanied by beneficial changes in animals' behavior. Despite the lack of antidepressant-properties of FLU in this model, our studies have proven significant profound anti-inflammatory properties of chronic FLU treatment which may suggest its suitability for fending off inflammatory processes in the elderly.


Assuntos
Anti-Inflamatórios/farmacologia , Antidepressivos/farmacologia , Citocinas/imunologia , Depressão/imunologia , Fluoxetina/farmacologia , Envelhecimento/imunologia , Animais , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Citocinas/genética , Depressão/tratamento farmacológico , Feminino , Fluoxetina/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipocampo/imunologia , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia
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