Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice

Background: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. Methods: Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calciumbinding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Results: MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were attenuated by CBD. CBD by itself did not induce any effect. Moreover, CBD effects were similar to those induced by repeated clozapine treatment

Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure

BACKGROUND: Physiological maternal stress response, such as imbalance in the glucocorticoid pathway and immune system seems to be mediated by DNA methylation (DNAm) and might translate intrauterine stress exposures into phenotypic changes in a sex-specific manner. DNAm in specific sites can also predict newborn gestational age and gestational age acceleration (GAA). GAA occurs when the predicted biological age is higher than the chronological age. In adults, poor health outcomes related to this deviance are well documented and raise questions for the interpretation and prediction in early stages of life. Boys seem to be more vulnerable to intrauterine stress exposure than girls; however, the mechanisms of adaptive sex-specific responses are still unclear. We hypothesize that intrauterine stress exposure is associated with GAA and could be different in boys and girls if inflammatory or glucocorticoid pathways exposure is considered. RESULTS: Using the Western Region Birth Cohort (ROC-Sao Paulo, Brazil) (n = 83), we calculated DNAm age and GAA from cord blood samples. Two epigenetic risk scores were calculated as an indirect proxy for low-grade inflammation (i-ePGS) and for glucocorticoid exposure (GES). Multivariate linear regression models were applied to investigate associations of GAA with prenatal exposures. The i-ePGS and GES were included in different models with the same co-variates considering sex interactions. The first multivariate model investigating inflammatory exposure (adj. R(2) = 0.31, p = < 0.001) showed that GAA was positively associated with i-ePGS (CI, 0.26-113.87, p = 0.049) and negative pregnancy-related feelings (CI, 0.04-0.48 p = 0.019). No sex interaction was observed. The second model investigating glucocorticoid exposure (adj. R(2) = 0.32, p = < 0.001) showed that the higher was the GAA was associated with a lower the lower was the GES in girls (CI, 0.04-2.55, p = 0.044). In both models, maternal self-reported mental disorder was negatively associated with GAA. CONCLUSION: Prenatal epigenetic score of exposure to low-grade inflammatory was a predictor of GAA for both sexes. Glucocorticoid epigenetic score seems to be more important to GAA in girls. This study supports the evidence of sex-specificity in stress response, suggesting the glucocorticoid as a possible pathway adopted by girls to accelerate the maturation in an adverse condition

Desempenho de luta e sobrevivência entre espécies de abelhas sem ferrão e abelhas africanizadas em confinamento.

Este estudo avaliou o desempenho de luta e a sobrevivência de três espécies de abelhas sem ferrão confinadas com abelhas africanizadas (Apis mellifera)

Coleta de recursos e atividade externa de abelhas campeiras de Scaptotrigona sp. e Plebeia aff. flavocincta (Hymenoptera, Apidae, Meliponini) no Semiárido da Caatinga.

Este trabalho avaliou a qualidade de recursos e a atividade externa de abelhas campeiras de Scaptotrigona sp. e Plebeia aff. flavocincta na Caatinga

Monitoring the degradation and the corrosion of naphthenic acids by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry and atomic force microscopy

AbstractAlthough the term “naphthenic acids” was originally used to describe acids that contain naphthenic rings, today this term is used in a more general sense and refers to all components in the acid extractable fraction. In crude oil, naphthenic acids exist as a complex mixture of compounds with broad polydispersity with respect to both molecular weight and structure. There has been increasing interest in the naphthenic acids in crude oil because of the corrosion problems that cause during oil refining. Herein, two powerful analytical tools, negative-ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry, ESI(-)FT-ICR MS and atomic force microscopy (AFM), were combined to monitor the thermal degradation of naphthenic acids and their corrosion effects on AISI 1020 steel, respectively. Two different acidic crude oils (TAN=2.38 and 4.79mgKOHg−1, and total sulfur=0.7993 and 1.0220wt%) have been submitted to thermal treatment at 280, 300 and 350°C during 2, 4 and 6h, and characterized by ESI(-)-FT-ICR MS, total acid number (TAN), and total sulfur. The AISI 1020 steel was analyzed by scanning electron microscopy (SEM) and AFM. Generally, heating the crude oil at 350°C in a period of 6h, it was observed that a high efficiency (≅80%) and selectivity of thermal decarboxylation process was monitored by decay of TAN (4.79→0.44mgKOHg−1). ESI(-)-FT-ICR MS results showed that naphthenic acid species remained after the heating have DBE ranging 1–12 and carbon number from C15 to C45. AFM topographic profile evidenced that the naphthenic acid corrosion of the crude oil with TAN of 4.73mgKOHg−1 on AISI 1020 steel was profoundly altered and a marked reduction in peak to peak height values (obtained by subtracting the value of the lowest peak by the highest peak in the topographic area examined). Optical images and microphotographs confirmed the presence of irregularities, characterizing the corrosion mechanism as pitting type. The naphthenic corrosion was also evidenced in samples with low TAN value (0.44mgKOHg−1)

Expression of sugarcane genes induced by inoculation with Gluconacetobacter diazotrophicus and Herbaspirillum rubrisubalbicans

Several Brazilian sugarcane varieties have the ability to grow with little addition of inorganic nitrogen fertilizers, showing high contributions of Biological Nitrogen Fixation (BNF). A particular type of nitrogen-fixing association has been described in this crop, where endophytic diazotrophs such as Gluconacetobacter diazotrophicus and Herbaspirillum spp. colonize plant tissues without causing disease symptoms. In order to gain insight into the role played by the sugarcane in the interaction between this plant and endophytic diazotrophs, we investigated gene expression profiles of sugarcane plants colonized by G. diazotrophicus and H. rubrisubalbicans by searching the sugarcane expressed sequence tag SUCEST Database (http://sucest.lad.ic.unicamp.br/en/). We produced an inventory of sugarcane genes, candidates for exclusive or preferential expression during the nitrogen-fixing association. This data suggests that the host plant might be actively involved in the establishment of the interaction with G. diazotrophicus and H. rubrisubalbicans.Diversos genótipos brasileiros de cana-de-açúcar são capazes de crescer com baixa adição de adubos nitrogenados, obtendo elevadas contribuições da Fixação Biológica de Nitrogênio (FBN). Um tipo especial de associação com bactérias fixadoras de nitrogênio foi descrito em cana-de-açúcar, onde as bactérias endofíticas, como Gluconacetobacter diazotrophicus e Herbaspirillum spp., colonizam o interior dos tecidos vegetais, sem causar sintomas de doença. Com o objetivo de tentar entender o papel da cana-de-açúcar nesse tipo de associação, nós investigamos os perfis de expressão gênica de plantas colonizadas pelos diazotróficos endofíticos, usando o banco de dados do SUCEST. Um catálogo com os genes de cana-de-açúcar que são candidatos a se expressar exclusivamente ou preferencialmente durante a associação foi gerado. Esses dados preliminares sugerem que a cana-de-açúcar deve ter uma participação ativa na interação, respondendo a diversos processos metabólicos durante a associação.199206Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

GABA<inf>A</inf> and NMDA receptor density alterations and their behavioral correlates in the gestational methylazoxymethanol acetate model for schizophrenia

Hippocampal hyperactivity driven by GABAergic interneuron deficits and NMDA receptor hypofunction is associated with the hyperdopaminergic state often observed in schizophrenia. Furthermore, previous research in the methylazoxymethanol acetate (MAM) rat model has demonstrated that repeated peripubertal diazepam administration can prevent the emergence of adult hippocampal hyperactivity, dopamine-system hyperactivity, and associated psychosis-relevant behaviors. Here, we sought to characterize hippocampal GABAA and NMDA receptors in MAM-treated rats and to elucidate the receptor mechanisms underlying the promising effects of peripubertal diazepam exposure. Quantitative receptor autoradiography was used to measure receptor density in the dorsal hippocampus CA1, ventral hippocampus CA1, and ventral subiculum. Specifically, [3H]-Ro15-4513 was used to quantify the density of α5GABAA receptors (α5GABAAR), [3H]-flumazenil to quantify α1-3;5GABAAR, and [3H]-MK801 to quantify NMDA receptors. MAM rats exhibited anxiety and schizophrenia-relevant behaviors as measured by elevated plus maze and amphetamine-induced hyperlocomotion (AIH), although diazepam only partially rescued these behaviors. α5GABAAR density was reduced in MAM-treated rats in all hippocampal sub-regions, and negatively correlated with AIH. Ventral hippocampus CA1 α5GABAAR density was positively correlated with anxiety-like behavior. Dorsal hippocampus CA1 NMDA receptor density was increased in MAM-treated rats, and positively correlated with AIH. [3H]-flumazenil revealed no significant effects. Finally, we found no significant effect of diazepam treatment on receptor densities, potentially related to the only partial rescue of schizophrenia-relevant phenotypes. Overall, our findings provide first evidence of α5GABAAR and NMDA receptor abnormalities in the MAM model, suggesting that more selective pharmacological agents may become a novel therapeutic mechanism in schizophrenia

Association of knowledge, preventive counseling and personal health behaviors on physical activity and consumption of fruits or vegetables in community health workers

Abstract\ud \ud Background\ud There is evidence that if a health professional is active and has a healthy diet, he/she is more likely to advise patients about the benefits of physical activity and healthy eating The aims of this study were to: (1) describe the personal physical activity, consumption of fruits and vegetables behaviors and nutritional status of community health workers; (2) evaluate the association between knowledge, delivery of preventive counseling and personal behaviors among community health workers.\ud \ud \ud Methods\ud This was a cross-sectional study conducted in a nationally sample of health professionals working in primary health care settings in Brazil in 2011. This survey was part of the second phase of the Guide for Useful Interventions for Activity in Brazil and Latin America project, and data were collected through telephone interviews of 269 community health workers from the Unified Health Care system of Brazil. We applied questionnaires about personal reported behaviors, knowledge and preventive counseling in physical activity and consumption of fruits and vegetables. We calculated the prevalence and associations between the variables with logistic regression.\ud \ud \ud Results\ud The proportion of community health workers that practiced 150 minutes per week of physical activity in leisure time or transportation was high (64.9%). Half of community health workers were overweight and only 26.2% reported consuming five portions/day of fruits or vegetables. Most community health workers reported counseling about physical activity for more than six months (59.7%), and most were not knowledgeable of the fruits and vegetables and physical activity recommendations. Meeting the fruits and vegetables recommendations was associated with correct knowledge (OR = 4.5; CI95% 1.03;19.7), with reporting 150 minutes or more of physical activity per week (OR = 2.0; CI95% 1.03;3.7) and with reporting physical activity in leisure time (OR = 2.0; CI95% 1.05;3.6). Regular physical activity counseling was associated with reporting 10–149 minutes per week (OR = 3.8; CI95% 1.1;13.3) and with more than 150 minutes of physical activity per week (OR = 4.9; CI95% 1.5;16.5).\ud \ud \ud Conclusion\ud Actions to promote physical activity and healthy eating and to improve knowledge among community health workers within the health care system of Brazil could have a potential positive influence on delivery of preventive counseling to patients on this topic