Chrysin restores memory deficit in hypothyroidism mice: Behavioral, neurochemical and computational approaches involving the neurotrophinergic system.

Hypothyroidism is a condition that affects multiple systems, including the central nervous system, causing, for example, cognitive deficits closely related to Alzheimer's disease. The flavonoid chrysin is a natural compound associated with neuronal improvement in several experimental models. Here, we evaluated the effect of chrysin on cognitive impairment in hypothyroid female mice by exploring neuroplasticity. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. On the 32nd day, the animals showed low plasma levels of thyroid hormones (hypothyroid mice) than the control group (euthyroid mice). Subsequently, mice were intragastrically administered with vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. At the end of the treatments, behavioral tests were performed: open-field test (OFT) and morris water maze (MWM). Then, the levels of neurotrophins (BDNF and NGF) in the hippocampus and prefrontal cortex were measured and tested the affinity of chrysin with neurotrophinergic receptors through molecular docking. Hypothyroid mice showed memory deficit in the MWM and reduced neurotrophins levels in the hippocampus and prefrontal cortex, meanwhile, the chrysin treatment was able to reversed the deficit of spatial memory function and increased the levels of BDNF in hipocamppus and NGF in both structures. Additionally, molecular docking analysis showed that chrysin potentially binds to the active site of the TrkA, TrkB, and p75NTR receptors. Together, these findings suggest that chrysin reversed behavioral and neurochemical alterations associated with memory deficit induced by hypothyroidism, possibly by modulating synaptic plasticity in the neurotrophinergic system.

Iron overload during the embryonic period develops hyperactive like behavior and dysregulation of biogenic amines in Drosophila melanogaster.

Iron (Fe) is used in various cellular functions, and a constant balance between its uptake, transport, storage, and use is necessary to maintain its homeostasis in the body. Changes in Fe metabolism with a consequent overload of this metal are related to neurological changes and cover a broad spectrum of diseases, mainly when these changes occur during the embryonic period. This work aimed to evaluate the effect of exposure to Fe overload during the embryonic period of Drosophila melanogaster. Progenitor flies (male and female) were exposed to ferrous sulfate (FeSO4) for ten days in concentrations of 0.5, 1, and 5 â€‹mM. After mating and oviposition, the progenitors were removed and the treatment bottles preserved, and the number of daily hatches and cumulative hatching of the first filial generation (F1) were counted. Subsequently, F1 flies (separated by sex) were subjected to behavioral tests such as negative geotaxis test, open field test, grooming, and aggression test. They have evaluated the levels of dopamine (DA), serotonin (5-HT), octopamine (OA), tryptophan and tyrosine hydroxylase (TH), acetylcholinesterase, reactive species, and the levels of Fe in the progenitor flies and F1. The Fe levels of F1 flies are directly proportional to what is incorporated during the period of embryonic development; we also observed a delay in hatching and a reduction in the number of the hatch of F1 flies exposed during the embryonic period to the 5mM Fe diet, a fact that may be related to the reduction of the cell viability of the ovarian tissue of progenitor flies. The flies exposed to Fe (1 and 5 â€‹mM) showed an increase in locomotor activity (hyperactivity) and a significantly higher number of repetitive movements. In addition to a high number of aggressive encounters when compared to control flies. We can also observe an increase in the levels of biogenic amines DA and 5-HT and an increase in TH activity in flies exposed to Fe (1 and 5 â€‹mM) compared to the control group. We conclude that the hyperactive-like behavior demonstrated in both sexes by F1 flies exposed to Fe may be associated with a dysregulation in the levels of DA and 5-HT since Fe is a cofactor of TH, which had its activity increased in this study. Therefore, more attention is needed during the embryonic development period for exposure to Fe overload.

Exercise associated with γ-oryzanol supplementation suppresses oxidative stress and prevents changes in locomotion in Drosophila melanogaster.

Association to early mortality and sedentarism was already demonstrated in the literature; nevertheless, some possible biochemical mechanisms around physical inactivity still need answers. The use of an invertebrate model, such as Drosophila melanogaster, can reproduce reliable responses in inducing an exercise protocol with exogenous antioxidant supplementation. This study main evaluates the effect of exercise (EXE) associated with γ-oryzanol (ORY) supplementation to improve locomotor behavior, antioxidant defenses, and survival in Drosophila melanogaster. Two-day old flies were submitted to a protocol for seven days, divided into five groups: Control, Movement-Limited Flies (MLF), EXE, ORY [25 µM], and EXE + ORY [25 µM]. The survival rate was evaluated, followed by open field and negative geotaxis. Flies were euthanized and subjected to analysis for acetylcholinesterase (AChE) and antioxidant enzymes activity, glycidic and lipid parameters, body weight, reactive species (RS), and lipid peroxidation. EXE and EXE + ORY flies showed increased survival and locomotor activity, improved glycidic and lipid parameters, with a lower RS production, and increased antioxidant defenses compared to Control, and EXE + ORY when compared to the EXE group, obtained an increase in the ratio of protein levels/body weight, decreased ratio of triglyceride levels/body weight and decreased lipid peroxidation. However, MLF showed less survival and decreased locomotor activity, possibly due to increased AChE activity and reduced antioxidant defenses. The EXE and EXE + ORY demonstrate effective results in maintaining endogenous defenses, with increased locomotor activity, supporting evidence on EXE benefits, and supplementation with antioxidant compounds face of health paradigms.HighlightsNew protocol system of exercise on Drosophila melanogaster model.ORY demonstrates synergistic effect with EXE.Exercise with ORY supplementation increases locomotor behavior.Exercise with ORY supplementation decrease oxidative damages on flies.

γ-Oryzanol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in Drosophila melanogaster.

Chronic unpredictable mild stress (CUMS) is a valid model for inducing depression-like symptoms in animal models, causing predictive behavioral, neurochemical, and physiological responses to this condition. This work aims to evaluate the possible antidepressant effect of γ-oryzanol (ORY) in the CUMS-induced depressive model in male Drosophila melanogaster. We will use the CUMS protocol to continue the study previously conducted by our research group, mimicking a depressive state in these insects. Male flies were subjected to various stressors according to a 10-day randomized schedule and concomitantly treated with ORY or fluoxetine (FLX). After the experimental period, in vivo behavioral tests were performed (open field, forced swimming, aggressiveness test, mating test, male virility, sucrose preference index and light/dark test) and ex vivo analyses measuring serotonin (5HT), dopamine (DA), octopamine (OCT) levels and body weight. We report here that ORY-treated flies and concomitant exposure to CUMS did not exhibit obvious behaviors such as prolonged immobility or increased aggressive behavior, reduced male mating and virility behavior, and anxiolytic behavior, in contrast to ORY, not altering sucrose preference and body weight flies exposed to CUMS. ORY effectively prevented 5HT and OCT reduction and partially protected against DA reduction. The data presented here are consistent and provide evidence for the use of ORY as a potential antidepressant compound.Lay SummaryFlies treated with ORY and concomitant exposure to CUMS did not exhibit obvious depressive-like behaviors, such as prolonged immobility in the FST or increased aggressive behavior, or reduced mating behavior, male virility, or anxiolytic behavior. ORY did not change the preference for sucrose and body weight of flies, about the levels of monoamines in the heads of flies, ORY was effective in preventing the reduction of 5HT and OCT, and we had partial protection of ORY for reducing the levels of DA.

Modulation of glutamate levels and Na+,K+-ATPase activity contributes to the chrysin memory recovery in hypothyroidism mice.

Abnormalities in the thyroid hormones, like in hypothyroidism, are closely related to dementia and Alzheimer's disease demonstrating the main symptom of these disorders: memory deficit. In this study we evaluated the effect of chrysin on deficit spatial and aversive memories and the contribution of glutamatergic, cholinergic pathways and Na+, K+-ATPase activity on hippocampus and prefrontal cortex in hypothyroid adult female mice C57BL/6. Hypothyroidism was induced by the continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. The exposure to MTZ was associated to low plasma levels of thyroid hormones (TH) compared to the control group on the 32nd. Subsequently, euthyroid and MTZ-induced hypothyroid mice received (intragastrically) either vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. After treatments mice performed the following behavioral assessments: open-field test (OFT), morris water maze (MWM) and passive avoidance test. Additionally, plasma TH levels were measured again, as well as glutamate levels, Na+,K+-ATPase and acetylcholinesterase (AChE) activities were analyzed in the hippocampus and prefrontal cortex of mice. Mice with hypothyroidism showed a deficit of spatial and aversive memory and chrysin treatment reversed these deficits. It also reduced the levels of glutamate and decreased Na+,K+-ATPase activity in both cerebral structures in the hypothyroid mice compared with the euthyroid ones, with the exception of glutamate in the hippocampus, which was a partial reversal. AChE activity was not altered by treatments. Together, our results demonstrate that chrysin normalized hippocampal glutamate levels and Na+,K+-ATPase activity, which could be involved in the reversal of memory deficit.

7-chloro-4-(phenylselanyl) quinoline prevents dopamine depletion in a Drosophila melanogaster model of Parkinson's-like disease.

Neurodegeneration in Parkinson's disease appears to be caused by multiple factors, including oxidative damage and an increase in acetylcholinesterase expression that can culminate in loss of dopaminergic neurons. A selenium-containing quinoline derivative, 7-chloro-4-(phenylselanyl) quinoline (4-PSQ), shows important pharmacological actions mainly attributed to its antioxidant and anticholinesterase properties. Thus, this study investigated the neuroprotective effect of 4-PSQ in a model of Parkinson's-like disease induced by rotenone (ROT) in Drosophila melanogaster and verified whether these effects are related to selenium levels. Adult flies were divided into: [1] control, [2] 4-PSQ (25 µM), [3] ROT (500 µM), and [4] 4-PSQ (25 µM) + ROT (500 µM) groups and exposed to a diet containing ROT and/or 4-PSQ for 7 days, according to their respective groups. Survival, behavioral, and ex vivo analyses were performed. Dopamine levels, reactive species levels (RS), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activity, and proteic thiol (PSH) and non-proteic thiol (NPSH) content in the head region were analyzed, while acetylcholinesterase (AChE) activity and selenium levels in the head and body regions were analyzed. 4-PSQ was able to reverse the ROT-induced deficits in flies, reestablish dopamine and selenium levels, reverse cholinergic deficits, improve motor function, and ameliorate mortality. Furthermore, 4-PSQ also reduced RS levels and LPO, and restored the activities of the antioxidant enzymes, SOD and CAT. Interestingly, a positive relationship between dopamine and selenium levels could be seen. Our results demonstrate the neuroprotective effect of 4-PSQ, and we suggest that the compound may act via different mechanisms, such as improving antioxidant defenses and consequently reducing oxidative damages, as well as having an anticholinesterase action, which together can prevent dopamine depletion, as these actions were correlated with the presence of selenium in the 4-PSQ molecule.

Antimicrobial Effect of 2-Phenylethynyl-Butyltellurium in Escherichia coli and Its Association with Oxidative Stress.

This study aimed to evaluate the antimicrobial activity of 2-phenylethynyl-butyltellurium (PEBT) in Escherichia coli and the relation to its pro-oxidant effect. For this, we carried out disk diffusion test, minimum inhibitory concentration (MIC) assay, and survival curve analysis. We also measured the level of extracellular reactive oxygen species (ROS), activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and level of non-protein thiols (NPSH). PEBT at 1.28 and 0.128 mg/disk exhibited antimicrobial capability in the disk diffusion test, with an MIC value of 1.92 mg/ml, whereas PEBT at 0.96, 1.92, and 3.84mg/ml inhibited bacterial growth after a 9-h exposure. PEBT at 3.84, 1.92, and 0.96 mg/ml increased extracellular ROS production, decreased the intracellular NPSH level, and reduced the SOD and CAT activities. Glutathione or ascorbic acid in the medium protected the bacterial cells from the antimicrobial effect of PEBT. In conclusion, PEBT exhibited antimicrobial activity against E. coli, involving the generation of ROS, oxidation of NPSH, and reduction of the antioxidant defenses in the bacterial cells.

Chronic unpredictable mild stress-induced depressive-like behavior and dysregulation of brain levels of biogenic amines in Drosophila melanogaster.

The etiopathogenesis of depression may involve repeated exposure to several unpredictable stressors. This study was conducted to investigate changes induced by chronic unpredictable mild stress (CUMS) and to assess behavioral and neurochemical changes that predict depressive-like behavior in Drosophila melanogaster. Male Drosophila melanogaster flies were exposed to CUMS with several stressors (cold, heat, starvation, and sleep deprivation) in an unpredictable and chronic manner for ten days. At the end of treatment, in vivo behavioral tests (open field, aggression, forced swimming, mating, light/dark box, male fertility evaluation, sucrose preference, weight evaluation) and ex vivo analyses (dopamine and serotonin levels) were performed. Using this CUMS model, we obtained results that contribute to the construction of a depressive model in Drosophila, where we reproduce some behavioral phenotypes corresponding to depressive symptoms, such as immobility in the forced swimming test, less exploration in the light/dark test, changes in mating behavior, changes in the aggressiveness test, reduced sucrose preference, and weight-loss, in addition to a significant reduction in the levels of serotonin and dopamine when compared to the control group. Fluoxetine was used in our study as a positive control to demonstrate that CUMS-induced depressive-like behaviors in flies can be reversed by antidepressants. In conclusion, male Drosophila melanogaster exposed to CUMS display a depressive-like phenotype, and, while this poses some limitations as an animal model for depression, it meets some of the criteria required to be a valid model, such as good face and construct validity.

Chrysin reverses the depressive-like behavior induced by hypothyroidism in female mice by regulating hippocampal serotonin and dopamine.

Hypothyroidism is often associated with psychiatric disorders such as depression. In this study, we evaluated the effect of chrysin on depressive-like behavior and monoamine levels in hypothyroid female mice. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. Exposure to MTZ was associated with low plasma levels of thyroid hormones T3 and T4 compared with the control group. Subsequently, euthyroid and MTZ-induced hypothyroid mice were intragastrically administered vehicle or chrysin (20mg/kg) once a day for 28 consecutive days. After treatments, the following behavioral assessments were performed: Open-Field Test (OFT), Tail suspension test (TST), and Forced Swimming Test (FST). Additionally, T3 and T4 levels were measured again, and serotonin (5HT), dopamine, and noradrenaline levels were analyzed in the prefrontal cortex and the hippocampus. Chrysin treatment could not reverse T3 and T4 levels. Hypothyroid mice showed an increased immobility time in TST and FST; chrysin treatment reversed these effects. Reduced levels of 5HT and dopamine in the prefrontal cortex and the hippocampus were observed in the hypothyroid mice than in the euthyroid mice. Chrysin treatment recovered 5HT content in both structures and dopamine content only in the hippocampus. Noradrenaline content was not altered by treatments. Together, our results have demonstrated that chrysin treatment reverses depressive-like behaviors in hypothyroid female mice and suggests the involvement of 5HT and dopamine in these effects.

Avaliação parasitológica de alfaces (Lactuca sativa)comercializadas em um município da fronteira oeste, Rio Grande do Sul, Brasil / Parasitological evaluation of lettuce ( Lactuca sativa ) commercialized in a municipalitys western border, Rio Grande do Sul, Brazil

O consumo da alface (Lactuca sativa) pode ser um importante meio de transmissão de váriasdoenças parasitárias. Assim, o controle parasitológico constitui um grande desafio quando se verificaa inclusão cada vez mais frequente de hortaliças na dieta da população mundial. O objetivo destetrabalho foi avaliar a contaminação por parasitos de interesse em saúde pública em alfaces (L. sativa)comercializadas no município de Itaqui, RS. No processo de amostragem, foram selecionadossupermercados e produtores locais da cidade de Itaqui. Foram investigadas 60 amostras de alface (Lsativa) da variedade crespa, sendo 30 de produtores locais e 30 dos mercados locais, todas adquiridasaleatoriamente. As amostras de alface foram acondicionadas em sacos de polietileno limpos eidentificados. As folhas foram separadas uma a uma e lavadas em recipientes de vidro esterilizadoscom 250 mL de água destilada. A água resultante do processo de lavagem foi analisada utilizando-setrês técnicas parasitológicas: exame direto, sedimentação espontânea (Lutz) e centrífugo-flutuaçãoem sulfato de zinco a 33 por cento (Faust). Para a caracterização morfológica dos parasitos, utilizou-semicroscópio óptico. Das 60 amostras analisadas, 29 (48,3 por cento) apresentaram algum tipo de parasito,das quais 19 (63,3 por cento) eram procedentes de produtores locais e 10 (36,7 por cento), dos mercados locais.Foram encontrados ovos de Ascaris sp (5 por cento) e cistos de Giardia lamblia (38 por cento) e Entamoeba sp(13 por cento). A verificação da presença de parasitos, sobretudo helmintos e protozoários, especialmenteem hortaliças, é de grande interesse para a saúde pública, visto que fornece subsídios para o serviçode vigilância sanitária sobre o estado higiênico desses produtos.

The consumption of lettuce (Lactuca sativa) can be an important means of transmission of severalparasitic diseases, so the increasing inclusion of vegetables in the diet of the world populationpresents an important challenge. The objective of this study was to evaluate the contamination oflettuce (L. sativa) marketed in the municipality of Itaqui (RS) by parasites of interest to public health.A sampling process was used, selecting supermarkets and local producers in the city of Itaqui. Weinvestigated 60 samples of lettuce (L. sativa) of the curly variety, from 30 local producers and 30local markets, all acquired at random. The lettuce samples were placed in clean plastic bags andidentified. The leaves were separated and washed in a glass container with 250 ml of sterile distilledwater. The wash water was analyzed using three parasitological techniques: direct examination,spontaneous sedimentation technique (Lutz) and flotation of zinc sulfate to 33 percent (Faust). Themorphological features of the parasite were examined by means of an optical microscope. Of the60 samples analyzed, 29 (48.33 percent) had some type of parasites. Of these, 19 (63.34 percent) were fromlocal producers and 10 (36.66 percent) from local markets. Eggs were found of Ascaris sp. (5 percent) andcysts of Giardia lamblia (38 percent) and Entamoeba sp. (13 percent). Checking for the presence of parasites,particularly helminths and protozoa, especially in vegetables, has great interest for public health,because it supplements health surveillance on the hygienic condition of the goods.