RESUMO
OBJECTIVES: Obesity is a metabolic and hormonal disorder with serious social and psychological impacts. There is a close relationship among obesity, neuroendocrine homeostasis and behavioral patterns. However, few data are available in the literature regarding this subject. This study assessed behavior and memory of adult obese rats by monosodium l-glutamate (MSG) neonatal treatment or highly palatable dietary treatment. METHODS: MSG obesity was induced by subcutaneous injections of MSG (4 mg/g) during the first 5 days of life (Ob-MSG); control group (C-MSG), received saline solution equimolar. Both groups were fed with commercial chow. To induce dietary obesity, 21-day-old rats were assigned to two experimental diets: highly palatable diet (Ob-Diet) and control diet (C-Diet) composed of commercial chow. Ninety-day-old animals were submitted to behavioral assessment by the open-field test and short- and long-term memory by the object recognition test. Biometric variables were obtained, the Lee index was calculated and mass of retroperitoneal and perigonadal fat pads was measured. Furthermore, an altered behavioral profile was investigated by quantification of plasmatic corticosterone, expression, and activity of hypothalamic extracellular signal-regulated kinase protein (ERK) 1 and 2. RESULTS: Increased Lee index and fat pads were observed in Ob-MSG and Ob-Diet groups. Ob-MSG presented a higher level of anxiety and impaired long-term memory compared to C-MSG, while there was no difference between Ob-Diet and C-Diet. The Ob-MSG group presented a higher level of plasmatic corticosterone and increased phosphorylation of hypothalamic ERK1 and 2. DISCUSSION: Both treatments induced obesity but only Ob-MSG showed altered behavioral parameters, which is related to increased concentration of corticosterone and hypothalamic ERK1 and 2 activation.
Assuntos
Corticosterona/sangue , Modelos Animais de Doenças , Hipotálamo/metabolismo , Sistema de Sinalização das MAP Quinases , Consolidação da Memória , Neurônios/metabolismo , Obesidade/metabolismo , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Corticosterona/agonistas , Ativação Enzimática/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/enzimologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Consolidação da Memória/efeitos dos fármacos , Memória de Longo Prazo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/química , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/química , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Obesidade/sangue , Obesidade/induzido quimicamente , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Distribuição Aleatória , Ratos Wistar , Glutamato de Sódio/toxicidadeRESUMO
The correct and early identification of humans and dogs infected with Leishmania are key steps in the control of leishmaniasis. Additionally, a method with high sensitivity and specificity at low cost that allows the screening of a large number of samples would be extremely valuable. In this study, we analyzed the potential of mitogen-activated protein kinase 3 (MAPK3) and mitogen-activated protein kinase 4 (MAPK4) proteins from Leishmania braziliensis to serve as antigen candidates for the serodiagnosis of human visceral and tegumentary leishmaniasis, as well as canine visceral disease. Moreover, we mapped linear B-cell epitopes in these proteins and selected those epitopes with sequences that were divergent in the corresponding orthologs in Homo sapiens, in Canis familiaris, and in Trypanosoma cruzi. We compared the performance of these peptides with the recombinant protein using ELISA. Both MAPK3 and MAPK4 recombinant proteins showed better specificity in the immunodiagnosis of human and canine leishmaniasis than soluble parasite antigens and the EIE-leishmaniose-visceral-canina-bio-manguinhos (EIE-LVC) kit. Furthermore, the performance of this serodiagnosis assay was improved using synthetic peptides corresponding to B-cell epitopes derived from both proteins.
Assuntos
Doenças do Cão/parasitologia , Epitopos de Linfócito B/química , Leishmania braziliensis/enzimologia , Leishmaniose/parasitologia , Leishmaniose/veterinária , Proteína Quinase 3 Ativada por Mitógeno/química , Proteínas Quinases Ativadas por Mitógeno/química , Proteínas de Protozoários/química , Sequência de Aminoácidos , Animais , Anticorpos/análise , Anticorpos/imunologia , Linhagem Celular , Doenças do Cão/diagnóstico , Doenças do Cão/imunologia , Cães , Mapeamento de Epitopos , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Humanos , Leishmania braziliensis/química , Leishmania braziliensis/genética , Leishmania braziliensis/imunologia , Leishmaniose/diagnóstico , Leishmaniose/imunologia , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/imunologia , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/imunologia , Modelos Moleculares , Dados de Sequência Molecular , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Alinhamento de Sequência , Testes SorológicosRESUMO
Diphenyl diselenide (PhSe)(2) is a synthetic organoselenium compound displaying glutathione peroxidase-like activity. Protective and antioxidant potential of (PhSe)(2) have been extensively investigated in in vivo and in vitro studies. In spite of this, there is a lack of studies addressed to the investigation of potential cytotoxic effect and signaling pathways modulated by this compound. Herein, we aimed to analyze the effects of 24-h treatment with (PhSe)(2) on cell viability and a possible modulation of signaling pathways in human neuroblastoma cell line SH-SY5Y. For this purpose, cells were incubated with (PhSe)(2) (0.3-30 µM) for 24 h and cell viability, apoptotic cell death and modulation of MAPKs (ERK1/2 and p38(MAPK)), and PKC substrates phosphorylation was determined. (PhSe)(2) treatment significantly decreased cell viability and increased the number of apoptotic cells with induction of PARP cleavage. An increase in ERK1/2 phosphorylation was observed at (PhSe)(2) 3 µM. In contrast, higher concentrations of the chalcogenide inhibited ERK1/2, p38(MAPK) and PKC substrate phosphorylation. Pre-treatment with ERK1/2 inhibitor, U0126, increased cell susceptibility to (PhSe)(2). Together, these data indicate a cytotoxic potential of (PhSe)(2) in a neuronal cell line, which appears to be mediated by the ERK1/2 pathway.