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1.
J Sleep Res ; 32(2): e13716, 2023 04.
Article in English | MEDLINE | ID: mdl-36053904

ABSTRACT

The pathophysiology of the restless legs syndrome (RLS) is related to dopaminergic dysfunction, reduced iron and variations in gene expression, such as the protein tyrosine phosphatase receptor type delta gene (PTPRD). Animal models could be key to achieving a mechanistic understanding of RLS and to facilitate efficient platforms for evaluating new therapeutics. Thus, the aim of this study was to evaluate the expression of PTPRD, of genes and proteins associated with RLS, the sleep patterns and the cardiovascular parameters in an animal model of RLS (spontaneously hypertensive rat [SHR]). Rats were divided into two groups: (i) Wistar-Kyoto and (ii) SHR. Cardiovascular parameters were assessed by tail plethysmography. Polysomnography was used to analyse the sleep pattern (24 h). For the PTPRD analyses, quantitative polymerase chain reaction (qPCR) and indirect enzyme-linked immunosorbent assay (ELISA) techniques were used. To evaluate the tyrosine hydroxylase enzyme, dopamine transporter (DAT) and type 2 dopaminergic receptor, qPCR and Western Blotting techniques were used. For the quantification of iron, ferritin and transferrin, the ELISA method was used. SHRs had higher blood pressure, alterations in sleep pattern, lower expression of protein content of PTPRD, lower expression of DAT, and lower serum concentrations of ferritin. These data suggest that the behavioural, physiological, and molecular changes observed in SHRs provide a useful animal model of RLS, reinforcing the importance of this strain as an animal model of this sleep disorder.


Subject(s)
Restless Legs Syndrome , Rats , Animals , Restless Legs Syndrome/genetics , Rats, Inbred WKY , Iron , Dopamine , Ferritins , Models, Animal , Rats, Inbred SHR , Protein Tyrosine Phosphatases
2.
Cells ; 11(14)2022 07 14.
Article in English | MEDLINE | ID: mdl-35883638

ABSTRACT

Neuronal hypothalamic insulin resistance is implicated in energy balance dysregulation and contributes to the pathogenesis of several neurodegenerative diseases. Its development has been intimately associated with a neuroinflammatory process mainly orchestrated by activated microglial cells. In this regard, our study aimed to investigate a target that is highly expressed in the hypothalamus and involved in the regulation of the inflammatory process, but still poorly investigated within the context of neuronal insulin resistance: the α7 nicotinic acetylcholine receptor (α7nAchR). Herein, we show that mHypoA-2/29 neurons exposed to pro-inflammatory microglial conditioned medium (MCM) showed higher expression of the pro-inflammatory cytokines IL-6, IL-1ß, and TNF-α, in addition to developing insulin resistance. Activation of α7nAchR with the selective agonist PNU-282987 prevented microglial-induced inflammation by inhibiting NF-κB nuclear translocation and increasing IL-10 and tristetraprolin (TTP) gene expression. The anti-inflammatory role of α7nAchR was also accompanied by an improvement in insulin sensitivity and lower activation of neurodegeneration-related markers, such as GSK3 and tau. In conclusion, we show that activation of α7nAchR anti-inflammatory signaling in hypothalamic neurons exerts neuroprotective effects and prevents the development of insulin resistance induced by pro-inflammatory mediators secreted by microglial cells.


Subject(s)
Insulin Resistance , alpha7 Nicotinic Acetylcholine Receptor , Animals , Benzamides , Bridged Bicyclo Compounds , Glycogen Synthase Kinase 3/metabolism , Hypothalamus/metabolism , Inflammation/pathology , Mice , Microglia/metabolism , Neurons/metabolism , alpha7 Nicotinic Acetylcholine Receptor/metabolism
3.
Int J Mol Sci ; 22(10)2021 May 19.
Article in English | MEDLINE | ID: mdl-34069652

ABSTRACT

Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of obesity because it negatively modulates the hypothalamic control of food intake due to metaflammation and lipotoxicity. The use of animal models, such as rodents, in conjunction with in vitro models of hypothalamic cells, can enhance the understanding of hypothalamic functions related to the control of energy balance, thereby providing knowledge about the impact of diet on the hypothalamus, in addition to targets for the development of new drugs that can be used in humans to decrease body weight. Recently, sphingolipids were described as having a lipotoxic effect in peripheral tissues and the central nervous system. Specifically, lipid overload, mainly from long-chain saturated fatty acids, such as palmitate, leads to excessive ceramide levels that can be sensed by the hypothalamus, triggering the dysregulation of energy balance control. However, no systematic review has been undertaken regarding studies of sphingolipids, particularly ceramide and sphingosine-1-phosphate (S1P), the hypothalamus, and obesity. This review confirms that ceramides are associated with hypothalamic dysfunction in response to metaflammation, endoplasmic reticulum (ER) stress, and lipotoxicity, leading to insulin/leptin resistance. However, in contrast to ceramide, S1P appears to be a central satiety factor in the hypothalamus. Thus, our work describes current evidence related to sphingolipids and their role in hypothalamic energy balance control. Hypothetically, the manipulation of sphingolipid levels could be useful in enabling clinicians to treat obesity, particularly by decreasing ceramide levels and the inflammation/endoplasmic reticulum stress induced in response to overfeeding with saturated fatty acids.


Subject(s)
Ceramides/metabolism , Energy Metabolism/physiology , Fatty Acids/physiology , Animals , Ceramides/physiology , Diet, High-Fat/adverse effects , Endoplasmic Reticulum Stress/drug effects , Fatty Acids/metabolism , Humans , Hypothalamus/metabolism , Hypothalamus/physiology , Insulin Resistance/physiology , Leptin/metabolism , Lysophospholipids/metabolism , Obesity/metabolism , Signal Transduction/physiology , Sphingolipids/metabolism , Sphingosine/analogs & derivatives , Sphingosine/metabolism
4.
Mol Nutr Food Res ; 65(10): e2000943, 2021 05.
Article in English | MEDLINE | ID: mdl-33650755

ABSTRACT

SCOPE: Coconut oil (CO) diets remain controversial due to the possible association with metabolic disorder and obesity. This study investigates the metabolic effects of a low amount of CO supplementation. METHODS AND RESULTS: Swiss male mice are assigned to be supplemented orally during 8 weeks with 300 µL of water for the control group (CV), 100 or 300 µL of CO (CO100 and CO300) and 100 or 300 µL of soybean oil (SO; SO100 and SO300). CO led to anxious behavior, increase in body weight gain, and adiposity. In the hypothalamus, CO and SO increase cytokines expression and pJNK, pNFKB, and TLR4 levels. Nevertheless, the adipose tissue presented increases macrophage infiltration, TNF-α and IL-6 after CO and SO consumption. IL-1B and CCL2 expression, pJNK and pNFKB levels increase only in CO300. In the hepatic tissue, CO increases TNF-α and chemokines expression. Neuronal cell line (mHypoA-2/29) exposed to serum from CO and SO mice shows increased NFKB migration to the nucleus, TNF-α, and NFKBia expression, but are prevented by inhibitor of TLR4 (TAK-242). CONCLUSIONS: These results show that a low-dose CO changes the behavioral pattern, induces inflammatory pathway activation, TLR4 expression in healthy mice, and stimulates the pro-inflammatory response through a TLR4-mediated mechanism.


Subject(s)
Behavior, Animal/drug effects , Coconut Oil/administration & dosage , Coconut Oil/adverse effects , Hypothalamic Diseases/chemically induced , Inflammation/chemically induced , Metabolic Diseases/chemically induced , Adiposity/drug effects , Animals , Blood Glucose/analysis , Dietary Supplements , Male , Mice , Motor Activity/drug effects , Toll-Like Receptor 4/antagonists & inhibitors , Toll-Like Receptor 4/physiology , Weight Gain/drug effects
5.
Rev. bras. med. trab ; 16(1): 2-9, jan.-mar-2018.
Article in English, Portuguese | LILACS | ID: biblio-882524

ABSTRACT

Contexto: Sabe-se que as doenças ocupacionais não prejudicam apenas a produtividade, por meio da diminuição da capacidade para o trabalho, mas também todos os aspectos relacionados à qualidade de vida do funcionário. Assim, a manutenção da capacidade para o trabalho relaciona-se com o estado de saúde para execução das atividades laborais. Essas, quando bem desenvolvidas, geram desfechos positivos para as organizações e os trabalhadores. Objetivo: Avaliar a relação entre qualidade de vida e capacidade de trabalho em servidores do Poder Judiciário. Métodos: Estudo observacional de corte transversal. Constituída por 88 servidores públicos do Poder Judiciário, de ambos os sexos, aleatorizados. Realizado no Tribunal de Justiça de Pernambuco, cidade do Recife. A coleta de dados ocorreu por meio de questionários, sobre o índice de capacidade para o trabalho, qualidade de vida e variáveis sociodemográficas. Para análise dos dados utilizou-se a correlação de Pearson. Resultados: 90,9% dos trabalhadores apresentaram uma renda de 5 ou mais salários mínimos, 73,9% trabalhavam até 6 horas por dia e 52,3% realizavam atividade física regular. Os trabalhadores apresentaram maiores correlações para capacidade do trabalho e qualidade de vida em praticantes de atividade física (R=0,60; p<0,001) e com menores horas de trabalho (R=0,61; p<0,001). Quanto ao sexo, ambos, feminino (R=0,62; p<0,001) e masculino (R=0,40; p<0,010), demonstraram relação moderada e significativa com qualidade de vida. Conclusão: A população de trabalhadores do Poder Judiciário do presente estudo apresentou correlação positiva quanto à capacidade para o trabalho e qualidade de vida geral, bem como nos domínios físico, social, psicológico e ambiental.


Background: As is known, occupational diseases hamper productivity by impairing not only the work ability, but also all the aspects related with the quality of life of employees. Maintenance of work ability is associated with the state of health needed to perform work activities, which when are properly done lead to satisfactory results for both organizations and workers. Objective: To investigate the relationship between quality of life and work ability among judicial employees. Methods: Cross-sectional observational study. The sample comprised 88 randomly selected judicial employees from both sexes. The study was conducted at the Court of Justice of Pernambuco, Recife, Brazil. Data collection was performed through questionnaires for sociodemographic variables, quality of life and Work Ability Index. Pearson's correlation was used for data analysis. Results: 90.9% of participants had income equivalent to 5 or more times the minimum wage; 73.9% worked up to 6 hours per day; and 52.3% reported regular practice of physical activity. Correlation between work ability and quality of life was stronger for the participants with regular practice of physical activity (R=0.60; p<0.001) and shorter working time (R=0.61; p<0.001). On analysis per sex, work ability exhibited significant and moderate correlation with quality of life for both males (R=0.62; p<0.001) and females (R=0.40; p<0.010). Conclusion: Relative to the analyzed sample of judicial employees positive correlation was found between work ability and overall quality of life, as well as with quality of life physical health, social, psychological and environment domains.


Subject(s)
Humans , Quality of Life , Work Capacity Evaluation , Occupational Health , Judiciary , Government Employees , Brazil , Cohort Studies
6.
Rev Bras Med Trab ; 16(1): 2-9, 2018.
Article in English | MEDLINE | ID: mdl-32270068

ABSTRACT

BACKGROUND: As is known, occupational diseases hamper productivity by impairing not only the work ability, but also all the aspects related with the quality of life of employees. Maintenance of work ability is associated with the state of health needed to perform work activities, which when are properly done lead to satisfactory results for both organizations and workers. OBJECTIVE: To investigate the relationship between quality of life and work ability among judicial employees. METHODS: Cross-sectional observational study. The sample comprised 88 randomly selected judicial employees from both sexes. The study was conducted at the Court of Justice of Pernambuco, Recife, Brazil. Data collection was performed through questionnaires for sociodemographic variables, quality of life and Work Ability Index. Pearson's correlation was used for data analysis. RESULTS: 90.9% of participants had income equivalent to 5 or more times the minimum wage; 73.9% worked up to 6 hours per day; and 52.3% reported regular practice of physical activity. Correlation between work ability and quality of life was stronger for the participants with regular practice of physical activity (R=0.60; p<0.001) and shorter working time (R=0.61; p<0.001). On analysis per sex, work ability exhibited significant and moderate correlation with quality of life for both males (R=0.62; p<0.001) and females (R=0.40; p<0.010). CONCLUSION: Relative to the analyzed sample of judicial employees positive correlation was found between work ability and overall quality of life, as well as with quality of life physical health, social, psychological and environment domains.


CONTEXTO: Sabe-se que as doenças ocupacionais não prejudicam apenas a produtividade, por meio da diminuição da capacidade para o trabalho, mas também todos os aspectos relacionados à qualidade de vida do funcionário. Assim, a manutenção dacapacidade para o trabalho relaciona-se com o estado de saúde para execução das atividades laborais. Essas, quando bem desenvolvidas, geram desfechos positivos para as organizações e os trabalhadores. OBJETIVO: Avaliar a relação entre qualidade de vida e capacidade de trabalho em servidores do Poder Judiciário. MÉTODOS: Estudo observacional de corte transversal. Constituída por 88servidores públicos do Poder Judiciário, de ambos os sexos, aleatorizados. Realizado no Tribunal de Justiça de Pernambuco, cidade do Recife. Acoleta de dados ocorreu por meio de questionários, sobre o índice de capacidade para o trabalho, qualidade de vida e variáveis sociodemográficas. Para análise dos dados utilizou-se a correlação de Pearson. RESULTADOS: 90,9% dos trabalhadores apresentaram uma renda de 5 ou mais salários mínimos, 73,9% trabalhavam até 6 horas por dia e 52,3% realizavam atividade física regular. Os trabalhadores apresentaram maiores correlações para capacidade do trabalho e qualidade de vida em praticantes de atividade física (R=0,60; p<0,001) e com menores horas de trabalho (R=0,61; p<0,001). Quanto ao sexo, ambos, feminino (R=0,62; p<0,001) e masculino (R=0,40; p<0,010), demonstraram relação moderada e significativa com qualidade de vida. CONCLUSÃO: A população de trabalhadores do Poder Judiciário do presente estudo apresentou correlação positiva quanto à capacidade para o trabalho e qualidade de vida geral, bem como nos domínios físico, social, psicológico e ambiental.

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