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Inflammation is a vital mechanism that defends the organism against infections and restores homeostasis. However, when inflammation becomes uncontrolled, it leads to chronic inflammation. The NLRP3 inflammasome is crucial in chronic inflammatory responses and has become a focal point in research for new anti-inflammatory therapies. Flavonoids like catechin, apigenin, and epicatechin are known for their bioactive properties (antioxidant, anti-inflammatory, etc.), but the mechanisms behind their anti-inflammatory actions remain unclear. This study aimed to explore the ability of various flavonoids (isolated and combined) to modulate the NLRP3 inflammasome using in silico and in vitro models. Computer simulations, such as molecular docking, molecular dynamics, and MM/GBSA calculations examined the interactions between bioactive molecules and NLRP3 PYD. THP1 cells were treated with LPS + nigericin to activate NLRP3, followed by flavonoid treatment at different concentrations. THP1-derived macrophages were also treated following NLRP3 activation protocols. The assays included colorimetric, fluorometric, microscopic, and molecular techniques. The results showed that catechin, apigenin, and epicatechin had high binding affinity to NLRP3 PYD, similar to the known NLRP3 inhibitor MCC950. These flavonoids, particularly at 1 µg/mL, 0.1 µg/mL, and 0.01 µg/mL, respectively, significantly reduced LPS + nigericin effects in both cell types and decreased pro-inflammatory cytokine, caspase-1, and NLRP3 gene expression, suggesting their potential as anti-inflammatory agents through NLRP3 modulation.
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INTRODUCTION: Neuropsychiatric diseases are responsible for one of the highest burden of morbidity and mortality worldwide. These illnesses include schizophrenia, bipolar disorder, and major depression. Individuals affected by these diseases may present mitochondrial dysfunction and oxidative stress. Additionally, patients also have increased peripheral and neural chronic inflammation. The Brazilian fruit, açaí, has been demonstrated to be a neuroprotective agent through its recovery of mitochondrial complex I activity. This extract has previously shown anti-inflammatory effects in inflammatory cells. However, there is a lack of understanding of potential anti-neuroinflammatory mechanisms, such as cell cycle involvement. OBJECTIVE: The objective of this study is to evaluate the anti-neuroinflammatory potential of an açaí extract in lipopolysaccharide-activated BV-2 microglia cells. METHODS: Açaí extract was produced and characterized through high performance liquid chromatography. Following açaí extraction and characterization, BV-2 microglia cells were activated with LPS and a dose-response curve was generated to select the most effective açaí dose to reduce cellular proliferation. This dose was then used to assess reactive oxygen species (ROS) production, double-strand DNA release, cell cycle modulation, and cytokine and caspase protein expression. RESULTS: Characterization of the açaí extract revealed 10 bioactive molecules. The extract reduced cellular proliferation, ROS production, and reduced pro-inflammatory cytokines and caspase 1 protein expression under 1 µg/mL in LPS-activated BV-2 microglia cells but had no effect on double strand DNA release. Additionally, açaí treatment caused cell cycle arrest, specifically within synthesis and G2/Mitosis phases. CONCLUSION: These results suggest that the freeze-dried hydroalcoholic açaí extract presents high anti-neuroinflammatory potential.
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Euterpe , Microglia , Extratos Vegetais , Animais , Linhagem Celular , Citocinas/metabolismo , Euterpe/química , Lipopolissacarídeos , Camundongos , Microglia/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Neurological disorders have been demonstrated to be associated with mitochondrial dysfunction. This impairment may lead to oxidative stress and neuroinflammation, specifically promoted by NLRP3 expression. Açaí (Euterpe oleracea Mart.) has been studied in this field, since it presents important biological activities. We investigated açaí extract's anti-neuroinflammatory capacity, through NLRP3 inflammasome modulation. Microglia (EOC 13.31) were exposed to LPS and nigericin, as agents of inflammatory induction, and treated with açaí extract. Additionally, we used lithium (Li) as an anti-inflammatory control. Three different experiment models were conducted: (1) isolated NLRP3 priming and activation signals; (2) combined NLRP3 priming and activation signals followed by açaí extract as a therapeutic agent; and (3) combined NLRP3 priming and activation signals with açaí extract as a preventive agent. Cells exposed to 0.1 µg/mL of LPS presented high proliferation and increased levels of NO, and ROS, while 0.1 µg/mL of açaí extract was capable to reduce cellular proliferation and recover levels of NO and ROS. Primed and activated cells presented increased levels of NLRP3, caspase-1, and IL-1ß, while açaí, Li, and orientin treatments reversed this impairment. We found that açaí, Li, and orientin were effective prophylactic treatments. Preventative treatment with Li and orientin was unable to avoid overexpression of IL-1ß compared to the positive control. However, orientin downregulated NLRP3 and caspase-1. Lastly, primed and activated cells impaired ATP production, which was prevented by pre-treatment with açaí, Li, and orientin. In conclusion, we suggest that açaí could be a potential agent to treat or prevent neuropsychiatric diseases related to neuroinflammation.
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Anti-Inflamatórios/farmacologia , Euterpe , Microglia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Caspase 1/metabolismo , Proliferação de Células/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/metabolismo , Nigericina/farmacologia , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Brain disorders (BD) including neuropsychiatric and neurodegenerative diseases, are often associated with impairments in mitochondrial function and oxidative damage that can lead to neuronal injury. The mitochondrial complex I enzyme is one of the main sites of ROS generation and is implicated in many BD pathophysiologies. Despite advances in therapeutics for BD management, conventional pharmacotherapy still cannot efficiently control neuronal redox imbalance and mitochondrial dysfunction. Araucaria angustifolia is one of the main pine species in South America and presents a notable therapeutic history in folk medicine. A. angustifolia extract (AAE), obtained from the natural waste named bracts, is rich in flavonoids; molecules able to regulate cell redox metabolism. We examined the effects of AAE on rotenone-induced mitochondrial complex I dysfunction in human dopaminergic SH-SY5Y cells. AAE restored complex I assembly and activity mainly through overexpression of NDUFS7 protein and NDUFV2 gene levels. These findings were accompanied by a reduction in the generation of neuronal reactive oxygen species and lipid peroxidation. Our data demonstrates, for the first time, that AAE exerts in vitro neuroprotective effects, thus making it an interesting source for future drug development in BD-associated mitochondrial dysfunctions.
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Araucaria/metabolismo , Complexo I de Transporte de Elétrons/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sementes/metabolismo , Apoptose/efeitos dos fármacos , Araucaria/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/metabolismo , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Rotenona/farmacologia , América do SulRESUMO
Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.
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Fator Neurotrófico Derivado do Encéfalo/análise , Lobo Frontal/química , Sucos de Frutas e Vegetais , Hipocampo/química , Subunidade beta da Proteína Ligante de Cálcio S100/análise , Vitis/química , Animais , Antioxidantes/farmacologia , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Alimentos Orgânicos , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Subunidade beta da Proteína Ligante de Cálcio S100/efeitos dos fármacosRESUMO
ABSTRACT Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.
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Animais , Masculino , Fator Neurotrófico Derivado do Encéfalo/análise , Vitis/química , Subunidade beta da Proteína Ligante de Cálcio S100/análise , Sucos de Frutas e Vegetais , Lobo Frontal/química , Hipocampo/química , Valores de Referência , Distribuição Aleatória , Reprodutibilidade dos Testes , Ratos Wistar , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Alimentos Orgânicos , Subunidade beta da Proteína Ligante de Cálcio S100/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Antioxidantes/farmacologiaRESUMO
Neuropsychiatric diseases, such as bipolar disorder (BD) and schizophrenia (SCZ), have a very complex pathophysiology. Several current studies describe an association between psychiatric illness and mitochondrial dysfunction and consequent cellular modifications, including lipid, protein, and DNA damage, caused by cellular oxidative stress. Euterpe oleracea (açaí) is a powerful antioxidant fruit. Açaí is an Amazonian palm fruit primarily found in the lowlands of the Amazonian rainforest, particularly in the floodplains of the Amazon River. Given this proposed association, this study analyzed the potential in vitro neuropharmacological effect of Euterpe oleracea (açaí) extract in the modulation of mitochondrial function and oxidative metabolism. SH-SY5Y cells were treated with rotenone to induce mitochondrial complex I dysfunction and before and after we exposed the cells to açaí extract at 5 µg/mL. Treated and untreated cells were then analyzed by spectrophotometric, fluorescent, immunological, and molecular assays. The results showed that açaí extract can potentially increase protein amount and enzyme activity of mitochondrial complex I, mainly through NDUFS7 and NDUFS8 overexpression. Açaí extract was also able to decrease cell reactive oxygen species levels and lipid peroxidation. We thus suggest açaí as a potential candidate for drug development and a possible alternative BD therapy.
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Euterpe/química , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Rotenona/toxicidade , Desacopladores/toxicidade , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Complexo I de Transporte de Elétrons/metabolismo , Frutas , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NADH Desidrogenase/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Espécies Reativas de Oxigênio/metabolismoRESUMO
The aim of this study was to elucidate whether glutathione is involved in lithium's ability to decrease carbonylation and nitration produced by complex I inhibition, which is consistently found in BD. Neuroblastoma cells were treated with rotenone, a complex I inhibitor. Our results suggest that glutathione is essential for lithium's ability to ameliorate rotenone-induced protein carbonylation, but not nitration.
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Complexo I de Transporte de Elétrons/antagonistas & inibidores , Glutationa/metabolismo , Compostos de Lítio/farmacologia , Carbonilação Proteica/efeitos dos fármacos , Tirosina/análogos & derivados , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Humanos , Imuno-Histoquímica , Neuroblastoma/metabolismo , Rotenona/farmacologia , Tirosina/metabolismo , Desacopladores/farmacologiaRESUMO
Diabetes mellitus is a disease associated with several changes in the central nervous system, including oxidative stress and abnormal glutamatergic neurotransmission, and the astrocytes play an essential role in these alterations. In vitro studies of astroglial function have been performed using cultures of primary astrocytes or C6 glioma cells. Herein, we investigated glutamate uptake, glutamine synthetase and S100B secretion in C6 glioma cells cultured in a high-glucose environment, as well as some parameters of oxidative stress and damage. C6 glioma cells, cultured in 12 mM glucose medium, exhibited signals of oxidative and nitrosative stress similar to those found in diabetes mellitus and other models of diabetic disease (decrease in glutathione, elevated NO, DNA damage). Interestingly, we found an increase in glutamate uptake and S100B secretion, and a decrease in glutamine synthetase, which might be linked to the altered glutamatergic communication in diabetes mellitus. Moreover, glutamate uptake in C6 glioma cells, like primary astrocytes, was stimulated by extracellular S100B. Aminoguanidine partially prevented the glial alterations induced by the 12 mM glucose medium. Together, these data emphasize the relevance of astroglia in diabetes mellitus, as well as the importance of glial parameters in the evaluation of diabetic disease progression and treatment.
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Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Glucose/metabolismo , Fatores de Crescimento Neural/metabolismo , Proteínas S100/metabolismo , Acetilcisteína/farmacologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Linhagem da Célula , Meios de Cultura , Dano ao DNA , Glioma/patologia , Guanidinas/farmacologia , Humanos , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
BACKGROUND: Dysregulation of HPA axis has been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naïve BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. METHODS: Twenty-six drug-naïve patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. RESULTS: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. LIMITATION: Data including larger samples are lacking. CONCLUSION: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD.
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Transtorno Bipolar/sangue , Hidrocortisona/sangue , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Euforia , Humanos , Humor Irritável , Adulto JovemRESUMO
The mechanisms by which resveratrol (3,5,4'-trihydroxy-stilbene) imparts neural effects is not well understood. We previously demonstrated that, depending upon the concentration of resveratrol and the cell type, this compound exerts anti-or pro-oxidant effects. In the present study, we investigated the effects of resveratrol on H(2)O(2)-mediated genotoxicity in C6 astroglial cells (I - 1mM H(2)O(2)/30 min or II - 0.1mM H(2)O(2)/6h), evaluated by micronucleus assay, lipid peroxidation (TBARS) and membrane integrity. H(2)O(2) increased micronuclei to 1.5 (I) and 1.7-fold (II), compared to control cells. This DNA damage was prevented (I) or partially prevented (II) by resveratrol. Oxidative insult also increased TBARS, 52% in I and 38% in II, P<0.05. These effects were prevented by resveratrol in I and increased in II (70% of increase). Present data contribute to the understanding of resveratrol effects under oxidative stress damage.
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Antioxidantes/farmacologia , Astrócitos/efeitos dos fármacos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/toxicidade , Oxidantes/toxicidade , Estilbenos/farmacologia , Animais , Ácido Ascórbico/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Corantes , Dano ao DNA , L-Lactato Desidrogenase/metabolismo , Lipídeos de Membrana/metabolismo , Testes para Micronúcleos , Oxirredução , Ratos , Resveratrol , Alcatrões/metabolismo , Sais de Tetrazólio , TiazóisRESUMO
CONTEXTO: O transtorno bipolar (TB) está associado a uma significativa morbi-mortalidade por causas metabólicas. Existem poucos dados sobre a prevalência de resistência à insulina (RI) e sua relação com a síndrome metabólica (SM) em pacientes com TB. OBJETIVO: Avaliar a prevalência de RI e SM em pacientes bipolares ambulatoriais e identificar os parâmetros clínicos associados à RI. MÉTODO: Estudo transversal em 65 pacientes com TB diagnosticados pelos critérios do DSM-IV-TR, avaliados de forma consecutiva no Programa de Transtorno Bipolar do Hospital de Clínicas de Porto Alegre, Brasil. RI foi diagnosticada utilizando o homeostatic model assessment - insulin resistance (HOMA-IR) e a SM foi diagnosticada utilizando três definições diferentes: do National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); do NCEP-ATP III modificado e da International Diabetes Federation (IDF). RESULTADOS: A prevalência de RI foi 43,1 por cento (mulheres 40 por cento, homens 44,4 por cento). A prevalência de SM definida pelo NCEP ATP III foi 32,3 por cento, pelo NCEP ATP III foi 40 por cento e pela IDF foi 41,5 por cento. Os critérios do NCEP ATP III modificado demonstrou a melhor relação entre sensibilidade (78,6 por cento) e especificidade (89,2 por cento) na detecção de RI. A circunferência da cintura foi o parâmetro clínico mais associado à RI. CONCLUSÃO: As definições atuais de SM podem identificar, com razoável sensibilidade e especificidade, RI em pacientes com TB. A obesidade abdominal é bastante associada à RI nessa população de pacientes.
BACKGROUND: Bipolar disorder (BD) is associated with significant morbidity and mortality from metabolic diseases. There is a paucity of data regarding insulin resistance (IR) and its relationship with the metabolic syndrome (MS) in bipolar patients. OBJECTIVE: To evaluate the prevalence of both IR and MS in BD outpatients and to assess clinical criteria associated with IR. METHOD: Cross-sectional study in 65 DSM-IV-TR BD patients consecutively assessed at the Bipolar Disorder Program at Hospital de Clínicas de Porto Alegre , Brazil. IR was diagnosed by the homeostatic model assessment - insulin resistance (HOMA-IR) and MS was diagnosed using three different definitions: National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); NCEP-ATP III modified criteria and International Diabetes Federation. RESULTS: IR was present in 43.1 percent of the sample (women 40 percent, men 44.4 percent). The prevalence of MS defined by the NCEP-ATP III criteria was 32.3 percent, NCEP-ATP III modified was 40 percent and IDF was 41.5 percent. NCEP-ATP III modified criteria showed the best trade-off between sensitivity (78.6 percent) and specificity (89.2 percent) to detect insulin resistance. Waist circumference was the clinical parameter most associated with IR. DISCUSSION: Current MS criteria may provide reasonable sensitivity and specificity for the detection of IR in BD patients. Abdominal obesity is closely related to IR in this patient population.
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Assistência Ambulatorial , Gordura Abdominal , Resistência à Insulina , Síndrome Metabólica , Transtorno Bipolar , Transtornos do HumorRESUMO
Caffeine is widely consumed in beverages and food, and its consumption in high doses is associated with anxiety increase. Stress situations are often associated to coffee consumption, and have a strong influence on oxidative DNA damage. As there are sex-specific differences in many metabolic, neurochemical and behavioral aspects, the aim of this study is to verify the interaction between chronic consumption of caffeine and chronic stress on anxiety and DNA breaks in the hippocampus on male and female rats. Wistar rats were submitted to restraint stress for at least 50 days. The diet consisted of standard rat chow and caffeine 0.3 or 1 g/L in drinking water "ad libitum" as the only drinking source. Controls received tap water. Anxiety-like behavior and DNA breaks in the hippocampus were evaluated. Caffeine consumption and chronic stress increased anxiety-like behavior as well as DNA breaks in the hippocampus of male rats. No effect on these parameters was observed in females. These results may be related to the presence of estradiol, which may have anxiolytic and neuroprotective properties.
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Ansiedade/fisiopatologia , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Quebras de DNA , Hipocampo/química , Estresse Fisiológico , Estresse Psicológico/fisiopatologia , Glândulas Suprarrenais/anatomia & histologia , Análise de Variância , Animais , Comportamento Animal , Cafeína/efeitos adversos , Cafeína/metabolismo , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/metabolismo , Corticosterona/sangue , Comportamento Exploratório , Feminino , Locomoção , Masculino , Aprendizagem em Labirinto , Tamanho do Órgão , Ratos , Ratos Wistar , Restrição Física , Caracteres SexuaisRESUMO
Accumulating evidence suggests that reduced levels of brain-derived neurotrophic factor (BDNF) in acute mood episodes may play an important role in the pathophysiology of bipolar disorder (BD). In order to assess changes in BDNF serum levels in BD patients before and after treatment for acute mania, ten bipolar patients were prospectively examined at inpatient unit admission and discharge. Diagnoses were made using the Structured Clinical Interview for DSM-IV, SCID-I. Serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were decreased in BD patients during mania when compared to controls (p=0.013) but this difference was no longer significant after treatment (p=0.126). A sharp increase in BDNF levels was found after treatment of the episode of acute mania (p=0.010). These findings suggest that the changes in BDNF serum levels may be associated with treatment response in acute mania. Further studies designed to validate the use of BDNF as a marker of treatment response in bipolar disorder are warranted.
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Antimaníacos/farmacologia , Transtorno Bipolar/sangue , Transtorno Bipolar/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Adolescente , Adulto , Biomarcadores/análise , Biomarcadores/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: As several lines of evidence point to irregular biological rhythms in bipolar disorder, and its disruption may lead to new illness episodes, having an instrument that measures biological rhythms is critical. This report describes the validation of a new instrument, the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), designed to assess biological rhythms in the clinical setting. METHODS: Eighty-one outpatients with a diagnosis of bipolar disorder and 79 control subjects matched for type of health service used, sex, age and educational level were consecutively recruited. After a pilot study, 18 items evaluating sleep, activities, social rhythm and eating pattern were probed for discriminant, content and construct validity, concurrent validity with the Pittsburgh Sleep Quality Index (PSQI), internal consistency and test-retest reliability. RESULTS: A three-factor solution, termed sleep/social rhythm factor, activity factor and feeding factor, provided the best theoretical and most parsimonious account of the data; items essentially loaded in factors as theoretically intended, with the exception of the sleep and social scales, which formed a single factor. Test-retest reliability and internal consistency were excellent. Highly significant differences between the two groups were found for the whole scale and for each BRIAN factor. Total BRIAN scores were highly correlated with the global PSQI score. DISCUSSION: The BRIAN scale presents a consistent profile of validity and reliability. Its use may help clinicians to better assess their patients and researchers to improve the evaluation of the impact of novel therapies targeting biological rhythm pathways.
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Transtorno Bipolar/diagnóstico , Ritmo Circadiano , Entrevista Psicológica , Adulto , Transtorno Bipolar/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Escalas de Graduação Psiquiátrica , Fatores de RiscoRESUMO
O presente estudo investigou o estresse parental em mães de crianças com Transtorno de Déficit de Atenção/Hiperatividade (TDAH) (n=30), de crianças com TDAH e comorbidade com o Transtorno Opositor Desafiador (TOD) (n=30), e com desenvolvimento típico (n=30). Além disso, foram investigadas possíveis correlações do estresse parental, com as estratégias de coping, apoio social e severidade do TDAH. As mães foram avaliadas a partir dos seguintes instrumentos: Questionário de Suporte Social (SSQ); Inventário de Coping Parental - Área da Saúde - CHIP; Questionário de Estresse Parental para Pais de Criança com Transtorno de Desenvolvimento; MTA SNAP-IV Escala de pontuação para pais e professores. Dentre outros fatores, os resultados indicaram que as mães das crianças com TDAH combinado e TDAH + TOD apresentaram mais estresse parental do que mães de crianças com desenvolvimento típico e que o apoio social, o coping auto-estima e médico atuaram como moderadores do estresse parental.
The present study has investigated the parental stress in mothers of children with Attention Deficit Hyperactivity Disorder (ADHD) (n=30), in mothers of children with co-morbidity with the Oppositional Defiant Disorder (ODD) (n=30), and in mothers of children with typical development (n=30). In addition, possible correlations of parental stress with coping strategies, social support and ADHD severity have been investigated. The mothers have been evaluated using the following instruments: (a) Social Support Questionnaire (SSQ); (b) Parental Coping Inventory - Health Area - CHIP; (c) Questionnaire of Parental Stress for Parents of Children with Development Disorder; (d) MTA SNAP-IV Teachers and Parents Rating Scale. The results indicated that mothers of children with ADHD and ADHD + ODD presented more parental stress than mothers of children with typical development. In addition, social support, self-esteem coping and medical coping moderated the parental stress effect.
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Humanos , Masculino , Feminino , Criança , Adulto , Pessoa de Meia-Idade , Adaptação Psicológica , Mães/psicologia , Apoio Social , Estresse Psicológico , Transtorno do Deficit de Atenção com Hiperatividade/psicologiaRESUMO
O presente estudo investigou o estresse parental em mães de crianças com Transtorno de Déficit de Atenção/Hiperatividade (TDAH) (n=30), de crianças com TDAH e comorbidade com o Transtorno Opositor Desafiador (TOD) (n=30), e com desenvolvimento típico (n=30). Além disso, foram investigadas possíveis correlações do estresse parental, com as estratégias de coping, apoio social e severidade do TDAH. As mães foram avaliadas a partir dos seguintes instrumentos: Questionário de Suporte Social (SSQ); Inventário de Coping Parental - Área da Saúde - CHIP; Questionário de Estresse Parental para Pais de Criança com Transtorno de Desenvolvimento; MTA SNAP-IV Escala de pontuação para pais e professores. Dentre outros fatores, os resultados indicaram que as mães das crianças com TDAH combinado e TDAH + TOD apresentaram mais estresse parental do que mães de crianças com desenvolvimento típico e que o apoio social, o coping auto-estima e médico atuaram como moderadores do estresse parental.(AU)
The present study has investigated the parental stress in mothers of children with Attention Deficit Hyperactivity Disorder (ADHD) (n=30), in mothers of children with co-morbidity with the Oppositional Defiant Disorder (ODD) (n=30), and in mothers of children with typical development (n=30). In addition, possible correlations of parental stress with coping strategies, social support and ADHD severity have been investigated. The mothers have been evaluated using the following instruments: (a) Social Support Questionnaire (SSQ); (b) Parental Coping Inventory - Health Area - CHIP; (c) Questionnaire of Parental Stress for Parents of Children with Development Disorder; (d) MTA SNAP-IV Teachers and Parents Rating Scale. The results indicated that mothers of children with ADHD and ADHD + ODD presented more parental stress than mothers of children with typical development. In addition, social support, self-esteem coping and medical coping moderated the parental stress effect.(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Adulto , Pessoa de Meia-Idade , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Mães/psicologia , Apoio Social , Adaptação Psicológica , Estresse PsicológicoRESUMO
A growing body of evidence has pointed to the blockade of the N-methyl-d-aspartate (NMDA) receptor signaling as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with ketamine and imipramine in rats. To this aim, rats were 14 days treated once a day with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open-field tests. Ketamine and imipramine, at the all doses tested, reduced immobility time, and increased both climbing and swimming time of rats compared to the saline group, without affecting spontaneous locomotor activity. Brain-derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine- and ketamine-treated rats by ELISA sandwich assay. Chronic administration of both drugs, ketamine and imipramine, did not modify BDNF protein levels in the rat hippocampus. In conclusion, our findings demonstrate for the first time that chronic administration of acute inactive doses of ketamine (5 mg/kg) becomes active after chronic treatment, while no signs of tolerance to the behavioural effects of ketamine were observed after chronic administration of acute active doses (10 and 15 mg/kg). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of mood disorders.
Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/efeitos dos fármacos , Ketamina/farmacologia , Animais , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Hipocampo/metabolismo , Imipramina/farmacologia , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
OBJECTIVE: The neurotrophins, antioxidant enzymes and oxidative markers have reciprocal interactions. This report verified in chronically stable medicated schizophrenic patients whether there are correlations between the serum levels of superoxide dismutase, a key enzyme in the antioxidant defense, thiobarbituric acid reactive substances, a direct index of lipid peroxidation, and brain-derived neurotrophic factor, the most widely distributed neurotrophin. METHOD: Sixty DSM-IV schizophrenic patients were included (43 males, 17 females). Mean age was 34.7 ± 10.8 years, mean age at first episode was 19.8 ± 7.9 years, and mean illness duration was 14.9 ± 8.5 years. Each subject had a blood sample collected for the determination of serum levels of brain-derived neurotrophic factor, thiobarbituric acid reactive substances and superoxide dismutase. RESULTS: Brain-derived neurotrophic factor levels showed a positive correlation with thiobarbituric acid reactive substances levels (r = 0.333, p = 0.009). Brain-derived neurotrophic factor levels were not correlated with superoxide dismutase levels (r = - 0.181, p = 0.166), and superoxide dismutase levels were not correlated with thiobarbituric acid reactive substances levels (r = 0.141, p = 0.284). CONCLUSIONS: The positive correlation between brain-derived neurotrophic factor and thiobarbituric acid reactive substances suggests the need of further investigation on intracellular interactions of neurotrophins, antioxidant enzymes and oxidative markers. In addition, this opens a venue for investigation on treatments for the prevention of neurotoxicity along the course of schizophrenia.
OBJETIVO: As neurotrofinas, enzimas antioxidantes e marcadores de oxidação têm interações. Este estudo verificou se existem correlações entre os níveis séricos de superóxido-dismutase, uma enzima chave na defesa antioxidante, os produtos de reação com o ácido tiobarbitúrico, um indicador direto de peroxidação lipídica, e o fator neurotrófico derivado do cérebro, a neurotrofina mais amplamente distribuída. MÉTODO: Sessenta pacientes portadores de Esquizofrenia pelo DSM-IV foram incluídos (43 homens, 17 mulheres), com idade média de 34,7 ± 10,8 anos, idade média no primeiro episódio de 19,8 ± 7,9 anos, e tempo médio de duração da doença de 14,9 ± 8,5 anos. Foi coletado sangue de cada sujeito para a determinação dos níveis séricos de fator neurotrófico derivado do cérebro, superóxido-dismutase e ácido tiobarbitúrico. RESULTADOS: Os níveis de fator neurotrófico derivado do cérebro se correlacionaram positivamente aos de ácido tiobarbitúrico (r = 0,333, p = 0,009) e não mostraram correlação com os de superóxido-dismutase (r = - 0,181, p = 0,166). Este último também não se correlacionou aos níveis de ácido tiobarbitúrico (r = 0,141, p = 0,284). CONCLUSÕES: A correlação positiva entre fator neurotrófico derivado do cérebro e ácido tiobarbitúrico direciona para investigações na interação intracelular entre neurotrofinas, enzimas antioxidantes e marcadores de oxidação, além de abrir perspectives para pesquisa em tratamentos para a prevenção da neurotoxicidade ao longo do curso da esquizofrenia.
Assuntos
Adulto , Feminino , Humanos , Masculino , Antipsicóticos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/sangue , Esquizofrenia/sangue , Superóxido Dismutase/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Doença Crônica , Estudos de Coortes , Fatores de Crescimento Neural/efeitos dos fármacos , Fatores de Crescimento Neural/metabolismo , Esquizofrenia/tratamento farmacológicoRESUMO
OBJECTIVE: Recent studies have suggested that oxidative stress and DNA damage may play a role in the pathophysiology of bipolar disorder (BD). We investigated the effects of the mood stabilizers lithium and valproate on amphetamine-induced DNA damage in an animal model of mania and their correlation with oxidative stress markers. METHODS: In the first experiment (reversal model), we treated adult male Wistar rats with D-amphetamine (AMPH) or saline for 14 days; between the 8th and 14th days, rats also received lithium, valproate or saline. In the second experiment (prevention model), rats received either lithium, valproate or saline for 14 days; between the 8th and 14th days, we added AMPH or saline. We evaluated DNA damage using single-cell gel electrophoresis (comet assay), and we assessed the mutagenic potential using the micronucleus test. We assessed oxidative stress levels by lipid peroxidation levels (TBARS) and antioxidant enzyme activities (superoxide dismutase and catalase). We assessed DNA damage and oxidative stress markers in blood/plasma and hippocampal samples. We evaluated mutagenesis in fresh lymphocytes. RESULTS: In both models, we found that AMPH increased peripheral and hippocampal DNA damage. The index of DNA damage correlated positively with lipid peroxidation, whereas lithium and valproate were able to modulate the oxidative balance and prevent recent damage to the DNA. However, lithium and valproate were not able to prevent micronucleus formation. CONCLUSION: Our results support the notion that lithium and valproate exert central and peripheral antioxidant-like properties. In addition, the protection to the integrity of DNA conferred by lithium seems to be limited to transient DNA damage and does not alter micronuclei formation.