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Major depressive disorder (MDD) leads to pervasive changes in the health of afflicted patients. Despite advances in the understanding of MDD and its treatment, profound innovation is needed to develop fast-onset antidepressants with higher effectiveness. When acutely administered, the endogenous nucleoside guanosine (GUO) shows fast-onset antidepressant-like effects in several mouse models, including the olfactory bulbectomy (OBX) rodent model. OBX is advocated to possess translational value and be suitable to assess the time course of depressive-like behavior in rodents. This study aimed at investigating the long-term behavioral and neurochemical effects of GUO in a mouse model of depression induced by bilateral bulbectomy (OBX). Mice were submitted to OBX and, after 14 days of recovery, received daily (ip) administration of 7.5 mg/kg GUO or 40 mg/kg imipramine (IMI) for 45 days. GUO and IMI reversed the OBX-induced hyperlocomotion and recognition memory impairment, hippocampal BDNF increase, and redox imbalance (ROS, NO, and GSH levels). GUO also mitigated the OBX-induced hippocampal neuroinflammation (IL-1, IL-6, TNF-α, INF-γ, and IL-10). Brain microPET imaging ([18F]FDG) shows that GUO also prevented the OBX-induced increase in hippocampal FDG metabolism. These results provide additional evidence for GUO antidepressant-like effects, associated with beneficial neurochemical outcomes relevant to counteract depression.
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OBJECTIVE: To describe the sociodemographic characteristics, functional capacity and vaccination status of older adults, and to verify the factors associated with the incomplete vaccination status and the absence of the vaccination card. METHOD: Cross-sectional and analytical study conducted with older adults living in the city of Uberaba (MG). The following analyzes were carried out: descriptive, bivariate and multinomial logistic regression (p<0.05). RESULTS: A total of 576 older adults participated. Most of them were women, in the 70-80 age group, with partner, low education and income, living with someone, independent in basic activities of daily living and with partial dependence on instrumental activities. The highest percentage was for older adults who had incomplete vaccination status, especially regarding the absence of immunization for Hepatitis B. Individual monthly income < 1 minimum wage (p=0.002) and single-person housing arrangement (p=0.010) were associated with the incomplete vaccination status, and the absence of the vaccination card, with the lowest level of education (p=0.039). CONCLUSION: Low income and education, as well as living alone, are factors associated with inadequate vaccination status among older adults in the community. The need for primary care nurses to develop strategies to increase vaccination coverage among older adults with these characteristics is emphasized.
Assuntos
Atividades Cotidianas , Vacinação , Idoso , Estudos Transversais , Escolaridade , Feminino , Humanos , Modelos LogísticosRESUMO
ABSTRACT Objective: To describe the sociodemographic characteristics, functional capacity and vaccination status of older adults, and to verify the factors associated with the incomplete vaccination status and the absence of the vaccination card. Method: Cross-sectional and analytical study conducted with older adults living in the city of Uberaba (MG). The following analyzes were carried out: descriptive, bivariate and multinomial logistic regression (p<0.05). Results: A total of 576 older adults participated. Most of them were women, in the 70-80 age group, with partner, low education and income, living with someone, independent in basic activities of daily living and with partial dependence on instrumental activities. The highest percentage was for older adults who had incomplete vaccination status, especially regarding the absence of immunization for Hepatitis B. Individual monthly income < 1 minimum wage (p=0.002) and single-person housing arrangement (p=0.010) were associated with the incomplete vaccination status, and the absence of the vaccination card, with the lowest level of education (p=0.039). Conclusion: Low income and education, as well as living alone, are factors associated with inadequate vaccination status among older adults in the community. The need for primary care nurses to develop strategies to increase vaccination coverage among older adults with these characteristics is emphasized.
RESUMEN Objetivo: Describir las caracteristicas sociodemograficas, la capacidad funcional y la situacion vacunal de los adultos mayores y comprobar los factores asociados con la situacion vacunal incompleta y la ausencia del carnet de vacunacion. Método: Se trata de un estudio transversal y analitico llevado a cabo con adultos mayores residentes en el area urbana de Uberaba, Minas Gerais, mediante un analisis descriptivo, bivariado y de regresion logistica multinomial (p<0,05). Resultados: Participaron 576 adultos mayores. Predominaban las mujeres de edad avanzada, 70├80 anos, con pareja, bajo nivel de escolaridad e ingresos, que vivian solas, independientes en las actividades basicas de la vida diaria y parcialmente dependientes de las actividades instrumentales. El porcentaje mas alto correspondia a los adultos mayores que tenian un estado de vacunacion incompleto, especialmente en lo que respecta a la ausencia de inmunizacion contra la hepatitis B. Los ingresos mensuales individuales ≤ 1 salario minimo (p=0,002) y la disposicion de una vivienda unifamiliar (p=0,010) estaban asociados con el estado de vacunacion incompleta, y la ausencia del carnet de vacunacion, con un nivel de escolaridad bajo (p=0,039). Conclusión: Los ingresos bajos y la educacion, asi como el hecho de vivir solo, son factores que estan asociados a un estado de vacunacion inadecuado en adultos mayores de la comunidad. Es importante que el enfermero de atencion primaria desarrolle estrategias para aumentar la cobertura de vacunacion entre los adultos mayores con dichas caracteristicas.
RESUMO Objetivo: Descrever as caracteristicas sociodemograficas, a capacidade funcional e a situacao vacinal de idosos, e verificar os fatores associados a situacao vacinal incompleta e a ausencia do cartao de vacinas. Método: Estudo transversal e analitico conduzido com idosos residentes na zona urbana de Uberaba (MG). Procedeu-se as analises descritiva, bivariada e regressao logistica multinomial (p<0,05). Resultados: Participaram 576 idosos. Predominaram os idosos do sexo feminino, na faixa etaria de 70├80 anos, com companheiro, baixa escolaridade e renda, que moravam acompanhados, independentes nas atividades basicas da vida diaria e com dependencia parcial nas atividades instrumentais. O maior percentual foi para os idosos que possuiam situacao vacinal incompleta, sobretudo em relacao a ausencia da imunizacao para Hepatite B. Foram associados a situacao vacinal incompleta a renda individual mensal ≤ 1 salario minimo (p=0,002) e o arranjo de moradia unipessoal (p=0,010); e a ausencia do cartao de vacinas, a menor escolaridade (p=0,039). Conclusão: As baixas renda e escolaridade, bem como residir sozinho, sao fatores associados as situacoes vacinais inadequadas dos idosos da comunidade. Ressalta-se a necessidade de que o enfermeiro da atencao primaria desenvolva estrategias para aumentar a cobertura vacinal entre os idosos com essas caracteristicas.
Assuntos
Vacinas , Saúde do Idoso , Imunização , Idoso , Enfermagem GeriátricaRESUMO
Patients with juvenile systemic lupus erythematosus (JSLE) usually have an increase in fat mass and decrease in lean body mass. The purpose of this study was to assess the effect of a nutritional intervention on changes in body composition and food consumption of adolescents with JSLE compared with a control group and its variation over time and to assess the association of total fat mass with clinical parameters. This randomized controlled study evaluated 31 girls. Body composition and food intake were evaluated at baseline. The patients were randomly allocated into a nutritional intervention group and a control group. The intervention group received monthly nutritional guidelines for 9 months. After this period, evaluations were repeated. The carbohydrates intake decreased in the intervention group compared with the control group (p = 0.031) at the end of the study period. Additionally, a significant decrease was observed in the intake of energy (p = 0.023), carbohydrates (p = 0.031), protein (p = 0.024), total fat (p = 0.027), saturated fat (p = 0.012), and trans fat (p = 0.029) in the intervention group between baseline and the end of the study. There was an average increase of 3.7 kg (95% CI 0.8-6.5) in the total fat mass (p = 0.013) and 0.36 kg/m2 (95% CI 0.10-0.62) in the appendicular fat mass (p = 0.007) in the control group during the study period; this finding was not observed in the intervention group. A 9-month nutritional intervention in JSLE patients improved their eating habits and protected against the excessive gain of weight and body fat.
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Composição Corporal/fisiologia , Dieta Saudável , Ingestão de Energia , Lúpus Eritematoso Sistêmico/fisiopatologia , Adolescente , Adulto , Brasil , Criança , Comportamento Alimentar , Feminino , Humanos , Aumento de Peso , Adulto JovemRESUMO
The aim of the study was to describe biomarkers of lipid metabolism associated with increased cardiovascular risk and their correlation with disease variables and markers of inflammation in adolescent females with systemic lupus erythematosus (SLE). This cross-sectional controlled study evaluated 33 adolescent females with juvenile SLE and 33 healthy controls. Anthropometric data, SLE disease activity index (SLEDAI), medications, proteinuria, ultra-sensitive C-reactive protein (us-CRP), lipid profile (total cholesterol, LDL-c, HDL-c and triglycerides), apolipoproteins A and B (Apo A-I and B), paraoxonase, and myeloperoxidase were evaluated. Median age of the patients and the median disease duration were 16.7 years and 54 months, respectively. SLEDAI scores above 4 were observed in 11 (33.3 %) patients. Moreover, 12 (36.4 %) patients were overweight, and 5 (15.2 %) had low height for age ratios. Dyslipidemia was observed in 13 (39.4 %) patients and in 7 (21.2 %) controls with a decrease in HDL-c concentrations in SLE patients even after adjustment for their nutritional status. In the group with SLE, us-CRP concentrations were inversely correlated with LDL-c/ApoB ratio (p = 0.031). After multivariate regression analysis, the SLE group showed lower concentration of Apo A-I and a decreased LDL-c/ApoB ratio. SLE adolescent females with low disease activity, with preserved kidney function and on low dose of corticosteroids, regardless of nutritional status and food intake, have proatherogenic lipid biomarkers, which may contribute to an increased atherosclerotic risk.
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Colesterol/sangue , Metabolismo dos Lipídeos/fisiologia , Lúpus Eritematoso Sistêmico/sangue , Triglicerídeos/sangue , Adolescente , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , Aterosclerose/sangue , Aterosclerose/etiologia , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Fatores de Risco , Adulto JovemRESUMO
Although adsorption is an essential step in the enzymatic hydrolysis of lignocellulosic materials, literature reports controversial results in relation to the adsorption of the cellulolitic enzymes on different biomasses/pretreatments, which makes difficult the description of this phenomenon in hydrolysis mathematical models. In this work, the adsorption of these enzymes on Avicel and sugarcane bagasse pretreated by the hydrothermal bagasse (HB) and organosolv bagasse (OB) methods was evaluated. The results have shown no significant adsorption of ß-glucosidase on Avicel or HB. Increasing solids concentration from 5% (w/v) to 10% (w/v) had no impact on the adsorption of cellulase on the different biomasses if stirring rates were high enough (>100 rpm for Avicel and >150 rpm for HB and OB). Adsorption equilibrium time was low for Avicel (10 Min) when compared with the lignocellulosic materials (120 Min). Adsorption isotherms determined at 4 and 50 °C have shown that for Avicel there was a decrease in the maximum adsorption capacity (Emax) with the temperature increase, whereas for HB increasing temperature increased Emax . Also, Emax increased with the content of lignin in the material. Adsorption studies of cellulase on lignin left after enzymatic digestion of HB show lower but significant adsorption capacity (Emax = 11.92 ± 0.76 mg/g).
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Celulase/química , Celulose/química , Lignina/química , Saccharum/química , beta-Glucosidase/química , Adsorção , Aspergillus niger/enzimologia , Sítios de Ligação , Cinética , Trichoderma/enzimologiaRESUMO
BACKGROUND: Locus of pain control (LPC) is characterized by the behavior of people coping with their health problems, as a result of their own actions (internal control) or external factors or other people (external control). This parameter can be associated with medication adherence, in addition to other psychosocial factors that may also influence this behavior. This study was performed to investigate the influence of the LPC on medication adherence in patients undergoing an orthopedic procedure. SUBJECTS AND METHODS: We conducted a prospective cohort study on patients who attended an orthopedic clinic for arthroscopy treatment. The patients' LPC and pain intensity data were obtained on the day of admission through the use of the LPC scale and the visual analog scale (VAS), respectively, both being validated tools. After arthroscopic surgery, the patients received drug prescriptions and were reassessed after 15 days regarding treatment adherence, using the Morisky test. A P-value <0.05 was considered statistically significant. RESULTS: We assessed 79 individuals from both the internal LPC group (n=35) and external LPC group (n=44) and found that there were no group differences in sex, affected limb, cause of injury, repetitive strain injury, duration of pain, or pain intensity. However, there was a higher proportion of patients in the external LPC group that adhered to the prescribed medication compared with the internal LPC group (P<0.01). CONCLUSION: The results showed that among patients who underwent an orthopedic procedure, there was a higher adherence rate to prescribed medication in the external LPC group compared with the internal LPC group.
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Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. Clinically, the disease is characterized by progressive neurological deterioration and renal failure, whose pathophysiology is still undefined. In the present study we investigated the effect of acute MMA administration on some important parameters of brain neurotransmission in cerebral cortex of rats, namely Na(+), K(+)-ATPase, ouabain-insensitive ATPases and acetylcholinesterase activities, in the presence or absence of kidney injury induced by gentamicin administration. Initially, thirty-day old Wistar rats received one intraperitoneal injection of saline or gentamicin (70 mg/kg). One hour after, the animals received three consecutive subcutaneous injections of MMA (1.67 µmol/g) or saline, with an 11 h interval between each injection. One hour after the last injection the animals were killed and the cerebral cortex isolated. MMA administration by itself was not able to modify Na(+), K(+)-ATPase, ATPases ouabain-insensitive or acetylcholinesterase activities in cerebral cortex of young rats. In rats receiving gentamicin simultaneously with MMA, it was observed an increase in the activity of acetylcholinesterase activity in cerebral cortex, without any alteration in the activity of the other studied enzymes. Therefore, it may be speculated that cholinergic imbalance may play a role in the pathogenesis of the brain damage. Furthermore, the pathophysiology of tissue damage cannot be exclusively attributed to MMA toxicity, and control of kidney function should be considered as a priority in the management of these patients, specifically during episodes of metabolic decompensation when MMA levels are higher.
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Acetilcolinesterase/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Inibidores da Colinesterase , Ácido Metilmalônico/farmacologia , Insuficiência Renal/enzimologia , Erros Inatos do Metabolismo dos Aminoácidos , Análise de Variância , Animais , Creatinina/sangue , Gentamicinas/toxicidade , Masculino , Degeneração Neural/patologia , Ouabaína/farmacologia , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Membranas Sinápticas/efeitos dos fármacos , Membranas Sinápticas/enzimologia , Membranas Sinápticas/metabolismo , Transmissão Sináptica/efeitos dos fármacosRESUMO
Creatine was previously shown to produce an antidepressant-like effect in the tail suspension test through a modulation of the dopaminergic system. In this study, the mechanisms underlying its antidepressant-like effect were further evaluated by investigating the involvement of the serotonergic system in its effect. The anti-immobility effect of creatine (1mg/kg) was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100mg/kg, i.p., for 4 consecutive days, an inhibitor of serotonin (5-HT) synthesis). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub-effective doses of WAY100635 (0.1mg/kg, s.c., a 5-HT1A receptor antagonist), 8-OH-DPAT (0.1mg/kg, i.p., a 5-HT1A receptor agonist) or selective serotonin reuptake inhibitors fluoxetine (5mg/kg, p.o.), paroxetine (0.1mg/kg, p.o.), citalopram (0.1mg/kg, p.o.) and sertraline (3mg/kg, p.o.) reduced the immobility time in the tail suspension test as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an interaction with 5-HT1A receptors. Of note, the present results also indicate that creatine improves the effectiveness of the selective serotonin reuptake inhibitors, a finding that may have therapeutic implications for the treatment of depressive disorders.
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Antidepressivos/farmacologia , Creatina/farmacologia , Depressão/tratamento farmacológico , Receptor 5-HT1A de Serotonina/metabolismo , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia , Animais , Transtorno Depressivo/tratamento farmacológico , Elevação dos Membros Posteriores/métodos , Humanos , Camundongos , Paroxetina/metabolismo , Serotonina/metabolismoRESUMO
The antidepressant-like activity of creatine in the tail suspension test (TST) was demonstrated previously by our group. In this study we investigated the involvement of the noradrenergic system in the antidepressant-like effect of creatine in the mouse TST. In the first set of experiments, creatine administered by i.c.v. route (1 µg/site) decreased the immobility time in the TST, suggesting the central effect of this compound. The anti-immobility effect of peripheral administration of creatine (1 mg/kg, p.o.) was prevented by the pretreatment of mice with α-methyl-p-tyrosine (100 mg/kg, i.p., inhibitor of tyrosine hydroxylase), prazosin (1 mg/kg, i.p., α1-adrenoceptor antagonist), but not by yohimbine (1 mg/kg, i.p., α2-adrenoceptor antagonist). Creatine (0.01 mg/kg, subeffective dose) in combination with subeffective doses of amitriptyline (1 mg/kg, p.o., tricyclic antidepressant), imipramine (0.1 mg/kg, p.o., tricyclic antidepressant), reboxetine (2 mg/kg, p.o., selective noradrenaline reuptake inhibitor) or phenylephrine (0.4 µg/site, i.c.v., α1-adrenoceptor agonist) reduced the immobility time in the TST as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of α1-adrenoceptor and that creatine produces synergistic effects in the TST with antidepressants that modulate noradrenaline transporter, suggesting that an improvement in the response to the antidepressant therapy may occur when creatine is combined with these antidepressants. Furthermore, the synergistic effect of creatine (0.01 mg/kg, p.o.) and reboxetine (2 mg/kg, p.o.) combination was abolished by the α1-adrenoceptor antagonist prazosin, indicating that the antidepressant-like effect of combined therapy is likely mediated by an activation of α1-adrenoceptor.
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Antidepressivos/uso terapêutico , Creatina/uso terapêutico , Depressão/tratamento farmacológico , Elevação dos Membros Posteriores/métodos , Receptores Adrenérgicos alfa 1/metabolismo , Adrenérgicos/farmacologia , Análise de Variância , Animais , Depressão/diagnóstico , Modelos Animais de Doenças , Interações Medicamentosas , Inibidores Enzimáticos/administração & dosagem , Comportamento Exploratório/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Camundongos , Fatores de Tempo , alfa-Metiltirosina/administração & dosagemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia avellanedae Lorentz ex Griseb is a plant employed in tropical America folk medicine for the treatment of several diseases, including depressive disorders. AIM OF THE STUDY: To investigate the ability of Tabebuia avellanedae ethanolic extract (EET) administered chronically to cause an antidepressant-like effect in the tail suspension test (TST), a predictive test of antidepressant activity, and to reverse behavioral (hyperactivity, anhedonic-like behavior and increased immobility time in the TST) and biochemical changes induced by olfactory bulbectomy (OB), a model of depression, in mice. MATERIALS AND METHODS: Mice were submitted to OB to induce depressive-related behaviors, which were evaluated in the open-field test (hyperactivity), splash test (loss of motivational and self-care behavior indicative of an anhedonic-like behavior) and TST (increased immobility time). Phosphorylation levels of Akt, GSK-3ß, ERK1/2 and CREB, as well as BDNF immunocontent, were evaluated in the hippocampus of bulbectomized mice or sham-operated mice treated for 14 days by p.o. route with EET or vehicle. RESULTS: EET (10 and 30mg/kg) given 14 days by p.o route to mice reduced the immobility time in the TST without altering locomotor activity, an indicative of an antidepressant-like effect. EET per se increased both CREB (Ser(133)) and GSK-3ß (Ser(9)) phosphorylation (at doses of 10-30 and 30mg/kg, respectively) in sham-operated mice. OB caused hyperactivity, loss of motivational and self-care behavior, increased immobility time in the TST and an increase in CREB and ERK1 phosphorylation, as well as BDNF immunocontent. EET abolished all these OB-induced alterations except the increment of CREB phosphorylation. Akt (Ser(473)) and ERK2 phosphorylation levels were not altered in any group. CONCLUSIONS: EET ability to abolish the behavioral changes induced by OB was accompanied by modulation of ERK1 and BDNF signaling pathways, being a promising target of EET. Results indicate that this plant could constitute an attractive strategy for the management of depressive disorders, once more validating the traditional use of this plant.
Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Tabebuia , Animais , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Etanol/química , Feminino , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Bulbo Olfatório/cirurgia , Fitoterapia , Casca de Planta , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Solventes/químicaRESUMO
The aim of this study was to investigate the antidepressant-like effect of fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 (AcOEt1 and 2), hexane (HEX), ethanolic (ET), and essential oil-free (EOF) fractions, as well as essential oil, the isolated compounds carnosol and betulinic acid in the tail suspension test, a predictive test of antidepressant activity. Swiss mice were acutely administered by oral route (p.o.) with fractions, essential oil or isolated compounds, 60 min before the tail suspension test or open-field test. All of them produced a significant antidepressant-like effect: AcOEt1, ET, EOF fractions and essential oil (0.1-100mg/kg, p.o); HEX (0.1-10mg/kg, p.o) and AcOEt2 fraction (0.1-1mg/kg, p.o), carnosol (0.01-0.1mg/kg, p.o.) isolated from the HEX fraction and betulinic acid (10mg/kg, p.o.), isolated from the AcOEt1 and AcOEt2 fractions. No psychostimulant effect was shown in the open-field test, indicating that the effects in the tail suspension test are specific. This study suggests that carnosol and betulinic acid could be responsible for the anti-immobility effect of extracts from R. officinalis.
Assuntos
Abietanos/administração & dosagem , Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Óleos Voláteis/administração & dosagem , Extratos Vegetais/administração & dosagem , Rosmarinus/química , Triterpenos/administração & dosagem , Abietanos/análise , Abietanos/isolamento & purificação , Animais , Antidepressivos/química , Antidepressivos/isolamento & purificação , Depressão/psicologia , Elevação dos Membros Posteriores , Humanos , Masculino , Camundongos , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Triterpenos Pentacíclicos , Extratos Vegetais/isolamento & purificação , Triterpenos/análise , Triterpenos/isolamento & purificação , Ácido BetulínicoRESUMO
PURPOSE: Physical activity is currently being considered an effective alternative in the treatment of depression. At the preclinical level, the voluntary running wheel is a useful method of increasing physical activity in rodents and induces an antidepressant-like effect in some behavioral paradigms. METHODS: This study investigated the effect of physical activity on a voluntary running wheel in mice submitted to the forced swimming test (FST) and tail suspension test, two predictive tests of antidepressant properties. Moreover, the influence of the inhibition of serotonin and noradrenaline synthesis as well as the inhibition of protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CAMK-II) activity by pharmacological agents in the antidepressant-like action of physical activity was investigated. RESULTS: Physical activity on a voluntary running wheel by 21 d produced a reduction in the immobility time in the FST and tail suspension test, without producing alteration on locomotor activity in the open-field test. The antidepressant-like effect in the FST elicited by physical activity lasted for 7 d after removal of the running wheel. The anti-immobility effect of physical activity was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (100 mg·kg, i.p., once a day, for four consecutive days, inhibitor of serotonin synthesis), α-methyl-p-tyrosine (100 mg·kg, i.p., an inhibitor of noradrenaline and dopamine synthesis), H-89 (1 µg per site, i.c.v., a PKA inhibitor), and KN-62 (1 µg per site, i.c.v., a CAMK-II inhibitor). CONCLUSIONS: Taken together, these results first suggest that the effect of physical activity on the FST is dependent on either the increase in the bioavailability of monoamines in the synaptic cleft or an activation of intracellular signaling pathways mediated by PKA and CAMK-II.
Assuntos
Condicionamento Físico Animal/psicologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/fisiologia , Elevação dos Membros Posteriores , Isoquinolinas/farmacologia , Masculino , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Sulfonamidas/farmacologiaRESUMO
The olfactory bulbectomy (OB) animal model of depression is a well-established model that is capable of detecting antidepressant activity following chronic drug therapy, and the surgery results in behavioral and biochemical changes that are reminiscent of various symptoms of depression. In the present study, we investigated the degree to which 14 days of p.o. administration of the classic antidepressant fluoxetine (10mg/kg) were able to reverse OB-induced changes in behavior (namely, hyperactivity in the open-field test and reduced motivational and self-care behaviors in the splash test) and in the activation of hippocampal cell signaling pathways that are thought to be involved in synaptic plasticity. OB caused significant increases in ERK1 and CREB (Ser(133)) phosphorylation and in the expression of BDNF immunocontent, all of which were prevented by fluoxetine administration. Moreover, fluoxetine administration also caused a significant decrease in ERK2 phosphorylation in mice that had undergone OB. Neither Akt nor GSK-3ß phosphorylation was altered in any experimental condition. In conclusion, the present study shows that OB can induce significant behavioral changes that are accompanied by the activation of hippocampal signaling pathways, namely the ERK1/CREB/BDNF pathway, which is involved in the synaptic plasticity. Conversely, fluoxetine prevented these OB-induced behavioral changes and avoided the activation of ERK1/CREB/BDNF in the hippocampus. Taken together, our results extend the data from the existing literature regarding OB-induced behavioral and neurochemical changes, and suggest a possible underlying mechanism that can account for the antidepressant effect of fluoxetine in this model.
Assuntos
Antidepressivos de Segunda Geração/farmacologia , Fluoxetina/farmacologia , Hipocampo/citologia , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Análise de Variância , Anedonia/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Feminino , Preferências Alimentares/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Hipocampo/efeitos dos fármacos , Hipercinese/tratamento farmacológico , Hipercinese/etiologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Transtornos do Olfato/complicações , Transtornos do Olfato/etiologia , Bulbo Olfatório/cirurgia , Proteína Oncogênica v-akt/metabolismoRESUMO
The olfactory bulbectomy (OB) is an animal model of depression that results in behavioral, neurochemical and neuroendocrinological changes, features comparable to those seen in depressive patients. This study investigated OB-induced alterations in locomotor activity and exploratory behavior in the open-field test, self-care and motivational behavior in the splash test, hyperactivity in the novel object test and novel cage test, and the influence of chronic treatment with fluoxetine (10mg/kg, p.o., once daily for 14days) on these parameters. Fluoxetine reversed OB-induced hyperactivity in the open-field test, locomotor hyperactivity and the increase in exploratory behavior induced by novelty in the novel object and novel cage tests, and the loss of self-care and motivational behavior in the splash test. Moreover, OB decreased the number of grooming and fecal boli in the open-field and novel cage tests, alterations that were not reversed by fluoxetine. OB caused an increase in hippocampal, but not in prefrontal acetylcholinesterase (AChE) activity. Fluoxetine was able to reverse the increase in hippocampal AChE activity induced by OB. Serum corticosterone was increased in SHAM and bulbectomized mice treated with fluoxetine. In conclusion, OB mice exhibited depressive-like behaviors associated with an increase in hippocampal AChE activity, effects that were reversed by chronic treatment with fluoxetine.
Assuntos
Acetilcolinesterase/metabolismo , Comportamento Animal/efeitos dos fármacos , Fluoxetina/farmacologia , Hipocampo/efeitos dos fármacos , Bulbo Olfatório/cirurgia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Corticosterona/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , CamundongosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Several species of Eugenia L. are used in folk medicine for the treatment of various diseases. Eugenia brasiliensis is used for the treatment of inflammatory diseases, whereas Eugenia. uniflora is used for the treatment of symptoms related to depression and mood disorders, and is used in Brazil by the Guarani Indians as a tonic stimulant. AIM OF THE STUDY: To investigate the antidepressant-like effect of hydroalcoholic extracts of different plant species of genus Eugenia and to characterize the participation of the monoaminergic systems in the mechanism of action of the specie that afforded the most prominent antidepressant-like efficacy. MATERIALS AND METHODS: In the first set of experiments, the effects of hydroalcoholic extracts of Eugenia beaurepaireana, Eugenia brasiliensis, Eugenia catharinae, Eugenia umbelliflora and Eugenia uniflora and the antidepressant fluoxetine (positive control) administered acutely by p.o. route were evaluated in the tail suspension test (TST) and locomotor activity was assessed in the open-field test in mice. In the second set of experiments, the involvement of the monoaminergic systems in the antidepressant-like activity of Eugenia brasiliensis was evaluated by treating mice with several pharmacological agonists and antagonists. The effects of the combined administration of sub-effective doses of Eugenia brasiliensis and the antidepressants fluoxetine, imipramine and bupropion were also evaluated. RESULTS: The administration of the extracts from Eugenia brasiliensis, Eugenia catharinae and Eugenia umbelliflora, but not Eugenia beaurepaireana and Eugenia uniflora, exerted a significant antidepressant-like effect, without altering locomotor activity. The behavioral profile was similar to fluoxetine. Pre-treatment of mice with ketanserin, haloperidol, SCH23390, sulpiride, prazosin and yohimbine prevented the reduction of immobility time induced by Eugenia brasiliensis. Treatment with sub-effective doses of WAY100635, SKF38393, apomorphine, phenylephrine, but not clonidine, combined with a sub-effective dose of Eugenia brasiliensis decreased the immobility time in the TST. Furthermore, the combined administration of sub-effectives doses of Eugenia brasiliensis with fluoxetine, imipramine and bupropion produced an antidepressant-like effect. CONCLUSIONS: This study show, for the first time, the antidepressant-like effect of species of the genus Eugenia, especially Eugenia brasiliensis, whose effects in the TST seem to be mediated by serotoninergic (5-HT(1A) and 5-HT(2) receptors), noradrenergic (α(1)-adrenoceptor) and dopaminergic (dopamine D(1) and D(2) receptors) systems.
Assuntos
Antidepressivos/uso terapêutico , Extratos Vegetais/uso terapêutico , Receptores de Amina Biogênica/fisiologia , Syzygium , Antagonistas Adrenérgicos/farmacologia , Animais , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Feminino , Elevação dos Membros Posteriores/fisiologia , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Extratos Vegetais/farmacologia , Receptores de Amina Biogênica/agonistas , Receptores de Amina Biogênica/antagonistas & inibidores , Antagonistas da Serotonina/farmacologiaRESUMO
BACKGROUND AND METHOD: In this work, the contribution of NMDA receptors to the antidepressant-like effect of adenosine in the forced swimming test (FST) was investigated. RESULTS: The pretreatment of mice with NMDA or D-serine was able to prevent the anti-immobility effect of either adenosine or MK-801 in the FST. In addition, the administration of a sub-effective dose of adenosine produced a synergistic effect with sub-effective doses of MK-801, ketamine and zinc chloride. Moreover, the immobility time of the mice treated with active doses of adenosine or N(6)-cyclohexyladenosine (CHA) plus MK-801 was not significantly different from that obtained with adenosine, CHA and MK-801 alone; by contrast, the combination between active doses of adenosine and CHA plus an active dose of the tricyclic antidepressant imipramine produced a greater effect in the FST than the administration of either drug alone. CONCLUSION: Together, the results suggest that the effect of adenosine in the FST is likely dependent on the inhibition of NMDA receptors mediated by the activation of adenosine A(1) receptors.
Assuntos
Adenosina/farmacologia , Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Receptores de N-Metil-D-Aspartato/metabolismo , Adenosina/administração & dosagem , Animais , Antidepressivos/administração & dosagem , Antidepressivos Tricíclicos/farmacologia , Cloretos/administração & dosagem , Cloretos/farmacologia , Maleato de Dizocilpina/administração & dosagem , Maleato de Dizocilpina/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Imipramina/administração & dosagem , Imipramina/farmacologia , Imobilização , Ketamina/administração & dosagem , Ketamina/farmacologia , Masculino , Camundongos , N-Metilaspartato/farmacologia , Receptor A1 de Adenosina/metabolismo , Serina/farmacologia , Natação , Fatores de Tempo , Compostos de Zinco/administração & dosagem , Compostos de Zinco/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Rosemary, Rosmarinus ofï¬cinalis L., has several therapeutic applications in folk medicine for the treatment of a wide range of diseases, including depression. AIM OF THE STUDY: To evaluate the ability of Rosmarinus ofï¬cinalis hydroalcoholic extract (ROHE), as compared to the positive control fluoxetine, to reverse behavioral (hyperactivity, anhedonic behavior and learning deficit in water maze) and biochemical alterations (serum glucose level and acetylcholinesterase, AChE, activity) induced by an animal model of depression, the olfactory bulbectomy (OB) in mice. MATERIALS AND METHODS: Locomotor and exploratory behavior was assessed in the open-field, novel object and novel cage tests, anhedonic behavior was assessed in the splash test; cognitive deficits were evaluated in the water maze task. For the first set of experiments, ROHE (10-300 mg/kg) or fluoxetine (10mg/kg) was administered once daily (p.o.) for 14 days after OB and the behavioral tests were performed. For the second set of experiments, serum glucose and hippocampal and cerebrocortical AChE activity were determined in OB and SHAM-operated mice treated orally with ROHE (10mg/kg), fluoxetine (10mg/kg) or vehicle. RESULTS: ROHE (10-300 mg/kg), similar to fluoxetine, reversed OB-induced hyperactivity, increased exploratory and anhedonic behavior. OB needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of SHAM mice in the test session (24h later), demonstrating a selective deficit in spatial learning, which was not reversed by ROHE or fluoxetine. A reduced serum glucose level and an increased hippocampal AChE activity were observed in bulbectomized mice; only the latter effect was reversed by fluoxetine, while both effects were reversed by ROHE. CONCLUSIONS: ROHE exerted an antidepressant-like effect in bulbectomized mice and was able to abolish AchE alterations and hypoglycemia, but not spatial learning deficit induced by OB. Overall, results suggest the potential of Rosmarinus officinalis for the treatment of depression, validating the traditional use of this plant.
Assuntos
Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Deficiências da Aprendizagem/metabolismo , Aprendizagem/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Rosmarinus , Acetilcolinesterase/metabolismo , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Glicemia/metabolismo , Depressão/complicações , Depressão/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Feminino , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipercinese/tratamento farmacológico , Hipercinese/etiologia , Hipercinese/metabolismo , Hipoglicemia/tratamento farmacológico , Deficiências da Aprendizagem/tratamento farmacológico , Deficiências da Aprendizagem/etiologia , Camundongos , Camundongos Endogâmicos , Bulbo Olfatório/cirurgia , Extratos Vegetais/farmacologiaRESUMO
Creatine has been shown to play a significant role in health and disease. However, studies concerning its effect on mood are scarce. This study investigated the effect of creatine (p.o.) in the tail suspension test, a predictive test of antidepressant activity. Creatine reduced the immobility time in the tail suspension test (0.1-1000 mg/kg, male and female mice), without affecting locomotor activity. Furthermore, the involvement of the dopaminergic system in creatine-induced antidepressant-like effect in male mice in the tail suspension test was investigated. The anti-immobility effect of creatine (1 mg/kg) was prevented by the pre-treatment of mice with haloperidol (0.2 mg/kg, intraperitoneal (i.p.) route, non-selective dopamine receptor antagonist), (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0.05 mg/kg, subcutaneous (s.c.) route, dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., dopamine D2 receptor antagonist). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub-effective doses of (1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine) hydrochloride (SKF38393; 0.1 mg/kg, s.c., dopamine D1 receptor agonist), apomorphine (0.5 µg/kg, i.p., preferential dopamine D2 receptor agonist) or bupropion (1 mg/kg, p.o., dopamine reuptake inhibitor with subtle activity on noradrenergic reuptake) reduced the immobility time in the tail suspension test as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of dopamine D1 and D2 receptors.
Assuntos
Creatina/metabolismo , Dopamina/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Creatina/administração & dosagem , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Modelos Animais de Doenças , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Receptores de Dopamina D1/efeitos dos fármacos , Receptores de Dopamina D2/efeitos dos fármacosRESUMO
This study aims to examine the antidepressant-like action of Ghrelin (Ghr), a hormone synthesized predominantly by gastrointestinal endocrine cells and released during periods of negative energy balance, in two behavioral models: tail suspension test (TST), a predictive model of antidepressant activity, and the olfactory bulbectomy (OB), an established animal model of depression. The reduction in the immobility time in the TST was the parameter used to assess antidepressant-like effect of Ghr. The depressive-like behavior in olfactory bulbectomized mice was inferred through the increase in the immobility time in the TST and the hyperlocomotor activity in the open-field test. Ghr produced antidepressant-like effect in TST (0.3 nmol/µl, i.c.v.), and reversed OB-induced depressive-like behavior. In conclusion, these results provide clear evidence that an acute administration of ghrelin produce antidepressant-like effect in the TST and OB.