Estudo da topologia de redes de conexão funcional no córtex sensorial primário e hipocampo durante o sono de ondas lentas

Complex network analysis is a powerful tool into research of complex systems like brain networks. This work aims to describe the topological changes in neural functional connectivity networks of neocortex and hippocampus during slow-wave sleep (SWS) in animals submited to a novel experience exposure. Slow-wave sleep is an important sleep stage where occurs reverberations of electrical activities patterns of wakeness, playing a fundamental role in memory consolidation. Although its importance there s a lack of studies that characterize the topological dynamical of functional connectivity networks during that sleep stage. There s no studies that describe the topological modifications that novel exposure leads to this networks. We have observed that several topological properties have been modified after novel exposure and this modification remains for a long time. Major part of this changes in topological properties by novel exposure are related to fault tolerance

Soybean glycinin improves HDL-C and suppresses the effects of rosuvastatin on hypercholesterolemic rats

Background: This study was an investigation of the effects of ingesting a daily dose of isolated glycinin soy protein (11S globulin), in association with rosuvastatin, on the control of hypercholesterolemia in experimental animals.Methods: Male Wistar rats were kept in individual cages under appropriate controlled conditions of temperature, light and humidity. The animals were divided into five groups (n = 9): 1) standard (STD): fed on casein as protein source; 2) hypercholesterolemic (HC): STD plus 1% cholesterol and 0.5% cholic acid; 3) HC+11S: hypercholesterolemic + glycinin (300 mg/kg/day); 4) HC+ROS: hypercholesterolemic + rosuvastatin (10 mg/kg/day); 5) HC+11S+ROS: HC diet, the 11S protein and the drug in the doses given in (3) and (4). The protein and the drug were administered by gavage for 28 days. The results indicated that the addition of 1% cholesterol and 0.5% cholic acid induced hypercholesterolemia in the animals without interfering with their weight gain.Results: A single daily dose of glycinin contributed an additional 2.8% of dietary protein intake and demonstrated its functional role, particularly in raising HDL-C, decreasing triglycerides in the liver and improving the atherogenic index in animals exposed to a hypercholesterolemic diet.Conclusion: Most of the beneficial effects of the isolated treatments disappeared when the drug (rosuvastatin) and the protein (glycinin) were taken simultaneously. The association was shown not to interact additively, as noted in the plasma levels of total cholesterol and non-HDL cholesterol, and in the significant increase of cholesterol in the liver. Studies are in progress to identify the effects of peptides derived from the 11S globulin and their role in cholesterol metabolism.

Ação local do alendronato sódico na reparação óssea de ratos espontaneamente hipertensos (SHR)

FUNDAMENTO: A hipertensão arterial é uma desordem caracterizada por alterações relevantes no tecido ósseo. O alendronato sódico tem indicação no tratamento de doenças ósseas, por causa de sua afinidade pela hidroxiapatita, inibindo as reabsorções ósseas. OBJETIVO: Analisar a ação local do alendronato sódico na reparação óssea de ratos espontaneamente hipertensos (SHR). MÉTODOS: Um defeito ósseo foi criado no fêmur esquerdo de 80 ratos. de acordo com o material utilizado no local, criaram-se quatro grupos: controle (C), amido (Am), alendronato 1 mol (A1) e alendronato 2 mol (A2). Após 7 e 21 dias, os animais foram sacrificados. Foram realizadas análises histológicas e histomorfométricas e os dados foram submetidos a análise de variância (ANOVA) e teste de Tukey (5%). RESULTADOS: Aos 7 dias, observou-se, na área do defeito, tecido conjuntivo com hemorragia e inflamação em todos os grupos. Alguns apresentavam matriz osteóide. Os grupos A1 e A2 apresentaram, ainda, uma rede de fibrina. Aos 21 dias, as trabéculas ósseas fechavam praticamente a extensão do defeito nos grupos C e Am. No grupo A1 de animais machos, observaram-se trabéculas que se irradiavam do canal medular até a área do defeito. Nos grupos A1 e A2, constatou-se apenas a presença de tecido conjuntivo com mínima deposição de osteóide. Um achado histológico marcante foi a formação de tecido ósseo extracortical subperiosteal nos animais dos grupos A1 e A2. CONCLUSÃO: Concluiu-se que a administração do alendronato sódico não contribuiu para o reparo ósseo nos ratos SHR, mas possivelmente tenha sido responsável pelas formações ósseas extracorticais observadas.

Comparison of caffeine-induced locomotor activity between adolescent and adult rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Administração repetida de baixas doses de reserpina: um possível modelo para o estudo de déficits cognitivos e motores associados à Doença de Parkinson

Parkinson's disease (PD) is one of the most common neurodegenerative brain disorders and is characterized primarily by a progressive degeneration of dopaminergic neurons nigroestriatais. The main symptoms of this disease are motor alterations (bradykinesia, rigidity, tremor at rest), which can be highly disabling in advanced stages of the condition. However, there are symptomatic manifestations other than motor impairment, such as changes in cognition, mood and sensory systems. Animal models that attempt to mimic clinical features of PD have been used to understand the behavioral and neural mechanisms underlying neurophysiological disturbance of this disease. However, most models promote an intense and immediate motor impairment, consistent with advanced stages of the disease, invalidating these studies for the evaluation of its progressive nature. The administration of reserpine (a monoamine depletor) in rodents has been considered an animal model for studying PD. Recently we found that reserpine (in doses lower than those usually employed to produce the motor symptoms) promotes a memory deficit in an aversive discrimination task, without changing the motor activity. It was suggested that the administration of this drug in low doses can be useful for the study of memory deficits found in PD. Corroborating this data, in another study, acute subcutaneous administration of reserpine, while preserving motor function, led to changes in emotional context-related (but not neutral) memory tasks. The goal of this research was to study the cognitive and motor deficits in rats repeatedly treated with low doses of reserpine, as a possible model that simulates the progressive nature of the PD. For this purpose, 5-month-old male Wistar rats were submitted to a repeated treatment with vehicle or different doses of reserpine on alternate days. Cognitive and motor parameters and possible changes in neuronal function were evaluated during treatment. The main findings were: repeated administration of 0.1 mg / kg of reserpine in rats is able to induce the gradual appearance of motor signs compatible with progressive features found in patients with PD; an increase in striatal levels of oxidative stress and changes in the concentrations of glutamate in the striatum were observed five days after the end of treatment; in animals repeatedly-treated with 0. 1 mg/kg, cognitive deficits were observed only after the onset of motor symptoms, but not prior to the onset of these symptoms; 0.2 mg / kg reserpine repeated treatment has jeopardized the cognitive assessment due to the presence of severe motor deficits. Thus, we suggest that the protocol of treatment with reserpine used in this work is a viable alternative for studies of the progressive appearance of parkinsonian signs in rats, especially concerning motor symptoms. As for the cognitive symptoms, we suggest that more studies are needed, possibly using other behavioral models, and / or changing the treatment regimen

Ritmo circadiano de atividade motora e distribuição diária dos comportamentos afiliativos ao longo da fase juvenil em saguis (callithrix jacchus)

The temporal allocation of the active phase in relation to light and dark cycle (LD) changes during puberty in humans, degus, rats and rhesus. In marmosets, the animal model used in several biomedical researches, there is evidence of a delay at the beginning of the active phase and an increase in total daily activity after onset of puberty. However, as this aspect was evaluated in animals maintained in natural environmental conditions, it was not possible to distinguish between the effects of puberty and of seasonality. Furthermore, as motor activity is the result of different behaviors in this species, it is also important to characterize the diurnal distribution of other behaviors in juvenile stage. With the aim of characterizing the circadian rhythm of motor activity and the diurnal profile of affiliative behavior in marmosets, the motor activity of 5 dyads juveniles between 4 and 12 months of age and their parents was recorded continuously for actímetro. The families were maintained under artificial LD 12:12 h, constant temperature and humidity. The duration of grooming behavior, proximity and social play among juveniles was recorded 2 times a week in sessions of 15 minutes each hour of the active phase. Afetr onset of puberty in juvenile, it was observed that there was no change in the parameters of circadian motor activity rhythm which were common to most animals. Despite the absence of pubertal modulation, it was observed that the circadian activity profiles have stronger synchrony between individuals of the same family than that of different families, which may indicate that the circadian activity rhythm was modulated by the dynamics of social interactions. In relation to age, the total daily activity and the ratio between evening and morning activity (EA/MA) were higher in juveniles than in adults, which may be associated with differences in the circadian timing system between age groups. Furthermore, the onset of the 10 consecutive hours of higher activity (M10) occurred earlier in adult males than in other members of the group, probably as a way to avoid competition for resources in one of the first activities of the day that is foraging. During the juvenile stage, there was an increase in total daily activity that may be associated with increased motor ability of juveniles. In addition to the circadian activity rhythm, the daytime profile of proximity and social play behaviors was similar between the 5th and 12th month of life of juveniles, in which the interval between 7- 10 h in the morning showed the highest values of proximity and lower values of play social. Moreover, the duration of the grooming showed a similar distribution to adults from the 8th month, wherein the higher values occurring at the interval between 11 14 h of day. Considering the results, the parameters of the circadian activity rhythm had a greater influence of social factors than puberty. In relation to age, there were no changes related to the allocation of the active phase in relation to the LD cycle, but total daily activity, the ratio AV/AM and the start of the M10 is possible to observe differences between juveniles and adults

Expressão de zif268 no cérebro do lagarto Tropidurus Hispidus após exploração de um ambiente enriquecido.

In the present work, we investigated behavioral changes associated with the increase in Zif268 protein expression within telencephalic areas of the tropical lizard Tropidurus hispidus that correspond to the mammalian hippocampus (HC). We used 13 male individuals of this species, collected at the Federal Agrotechnical School of Rio Grande do Norte, under SISBIO license number 19561-1. Four animals had their brains removed and were submitted to a Western blot with antibodies for the Zif268 protein. The remaining animals were separated in two different groups: a control group (n=4) and an exploration group (n=5). Animals from the exploration group were exposed to an enriched environment with many sensory cues novel to them. Control group animals stayed in the environment they were already habituated to. After 90 min from the onset of exposure to the new environment, animals from both groups were submitted to intracardiac perfusion with fixative, and the brains were removed, cryoprotected and frozen. After that, brains were sectioned at 20 μm and the sections were subjected to immunohistochemistry for the Zif268 protein. We verified that the Zif268 protein is likely conserved in the brain of T. hispidus, which showed antigenicity for the antibody anti-Zif268 made in mammals. In animals from the exploration group, we detected an increase of the Zif268 protein in the Septum, Striatum, Dorsoventricular Area and in cortical areas corresponding to the HC. This increase was proportional to the amount of environmental exploration, with maximum positive correlation in the hippocampal subareas Medial Cortex (R = 0.94 and p = 0.004) and Dorsomedial Cortex (R = 0.92 and p = 0.006). The data corroborate the notion that the reptilian hippocampus, as well as the mammalian HC, plays an important role in spatial exploration.

Sincronização dos ritmos de atividade motora e temperatura central à disponibilidade de glicose em ratos

Food is essential for the survival of all animals. Its temporal availability is an important enviromental cue for the behavioral and physiological organization throughout the 24 hours of day in different species. Rats and mice, for example, show increased locomotion in the hours before food availability when it is presented in a recurrent manner, a behavior named foodanticipatory activity. Several lines of evidence indicate that this anticipation is mediated by a circadian oscillator. In this work, based on the hypothesis that pre- or post-ingestive humoral signals are involved in the entrainment process, we tested whether the daily intake of glucose is sufficient to induce anticipatory activity in rats. The rhythms of motor activity and central temperature were recorded in animals undergoing 10 days of temporal glucose (solution at 50%) or chow restriction in light-dark (LD) and constant darkness (DD). Animals under temporal glucose restriction increase motor activity and and central temperature in the hours preceding glucose availability and such aticipation is extremely similar to that observed in animals under temporal chow restriction. Glucose ingestion is, therefore, a sufficient temporal cue to induce anticipation in rats. It is possible that the increase in plasma glucose after food ingestion constitutes one of the signals involved in the behavioral entrainment process to food availability

Estudo dos efeitos comportamentais do neuropeptídeos em camundongos submetidos a modelos animais de Parkinson

Neuropeptide S (NPS) is the endogenous ligand of a G-protein coupled receptor. Preclinical studies have shown that NPSR receptor activation can promote arousal, anxiolytic-like behavioral, decrease in food intake, besides hyperlocomotion, which is a robust but not well understood phenomenon. Previous findings suggest that dopamine transmission plays a crucial role in NPS hyperactivity. Considering the close relationship between dopamine and Parkinson Disease (PD), and also that NPSR receptors are expressed on dopaminergic nuclei in the brain, the current study attempted to investigate the effects of NPS in motor deficits induced by intracerebroventricular (icv) administration of 6-OHDA and systemic administration of haloperidol. Motor deficits induced by 6-OHDA and haloperidol were evaluated on Swiss mice in the rota-rod and catalepsy test. Time on the rotating rod and time spent immobile in the elevated bar were measured respectively in each test. L-Dopa, a classic antiparkinsonian drug, and NPS were administrated in mice submitted to one of the animal models of PD related above. 6-OHDA injection evoked severe motor impairments in rota-rod test, while the cataleptic behavior of 6-OHDA injected mice was largely variable. The administration of L-Dopa (25 mg/kg) and NPS (0,1 and 1 nmol) reversed motor impairments induced by 6-OHDA in the rota-rod. Haloperidolinduced motor deficits on rota-rod and catalepsy tests which were reversed by L-Dopa (100 e 400 mg/kg), but not by NPS (0,1 and 1 nmol) administration. The association of L-Dopa 10 mg/kg and NPS 1 nmol was also unable to counteract haloperidol-induced motor deficits. To summarize, 6-OHDA-, but not haloperidol-, induced motor deficits were reversed by the central administration of NPS. These data suggest that NPS possibly facilitates dopamine release in basal ganglia, what would explain the overcome of motor performance promoted by NPS administration in animals pretreated with 6-OHDA, but not haloperidol. Finally, the presented findings point, for the first time, to the potential of NPSR agonist as an innovative treatment for PD.

Alterações cognitivas em ratos infectados com Toxoplasma gondii

Toxoplasma gondii is a protozoan parasite that induces behavioral changes in rodents. The aim of this study was to evaluate the effect of infection by T. gondii during the chronic phase in working memory and impulsivity in rodents as well as the effect of antipsychotics to reverse any behavioral changes resulting from infection. Female Wistar rats (n = 40) were infected with 25 cysts of the strain ME-49 T. gondii after 4 months the animals were subjected to behavioral tests: tolerance to delay gratification, in which the animal must choose between two rewards, a smaller and more immediate, but delayed and the test of spontaneous alternation, in which the animal must use spatial cues to remember previously visited arms. Antipsychotic drugs were intraperitoneally administered during the testing of the behavioral experiments, the antipsychotic is haloperidol (1.5 mg / kg) administered 60 min before the start of the session and the antipsychotic clozapine (2.5 mg / kg) 30 min before. Animals infected with the parasite did not show operating deficits of memory, and motor impairment did not develop, however motor impairment was observed only in animals treated with haloperidol. It was found that administration of clozapine and haloperidol increased the percentage of alternation in infected and control groups in task switching espontânea.Não no distinction between control animals and infected the test of tolerance to delay gratification in relation to the percentage of choices greatest reward, during the pre-training and training, in which there is a delay of 15 s to access the great reward, however it was observed that infected animals prefer the greatest reward, when there is a delay of 30 s when compared to control group. The administration of clozapine possible that infected animals chose the greatest reward in the delay of 30 seconds during the test. These data suggest that infected mice do not exhibit deficits in working memory and that clozapine has therapeutic efficacy in improving cognitive performance of mice infected

Efeitos de diferentes tipos estressores sobre a memória e aprendizagem de ratas

The exposure to stressors produces physiological changes of the organism in order to adapt the individual to the environment. Depending on the type, intensity and duration, stress can affect some cognitive functions, particularly processes of learning and memory. Several studies have also proposed that some level of anxiety would be necessary for memory formation. In this context, memories of previously aversive experiences may determine the manner and intensity with which are expressed fear responses, which explains the great interest in analyzing both anxiety and memory in animals. In addition, males and females demonstrate different reactions in relation to stressful stimuli, showing different levels of anxiety and differences in processing of the acquisition, retention and recall of information. Based on this information, the present study aimed to verify the effect of stress on learning, memory and anxiety behavioral parameters in rats exposed at different types of stressors of long duration (seven consecutive days): restraint (4h/day), overcrowding (18h/day) and social isolation (18h/day) in the different phases of the estrous cycle. Our results showed that the stress induced by restraint and social isolation did not cause changes in the acquisition process, but impaired the recall of memory in rats. Furthermore, it is suggested a protective effect of sex hormones on retrieval of aversive memory, since female rats in proestrus or estrus phase, characterized by high estrogen concentrations, showed no aversive memory deficits. Furthermore, despite the increased plasma levels of corticosterone observed in female rats subjected to restraint stress and social isolation, anxiety levels were unaltered, compared to those various stress conditions. Animal models based on psychological and social stress have been extensively discussed in the literature. Correlate behavioral responses, physiological and psychological have contributed in increasing the understanding of stress-induced psychophysiological disorders

O Tratamento com a fluoxetina (mas não com outros farmacos antidepressivo e ansioíiticos) reverte o déficit de memória aversiva causado por estresse agudo de contenção em camundongos

The physiologist H. Selye defined stress as the nonspecific response of the body to any factors that endanger homeostasis (balance of internal environment) of the individual. These factors, agents stressors, are able to activate the Hypothalamic-Pituitary-Adrenal (HPA) axis, thus resulting in the physiological responses to stress by the release of glucocorticoids that leads to psychophysiological changes, including effects on cognitive functions such as learning and memory. When this axis is acutely stimulated occurs a repertoire of behavioral and physiological changes can be adaptive to the individual. Notwithstanding, when the HPA axis is chronically stimulated, changes may favor the development of, such as anxiety disorders. Some drugs used in the clinic for the treatment of anxiety disorders these can exert effects on cognitive function, on the HPA axis and on the anxiety. In this context, the aim of our study was to investigate the effects of administration i.p. acute of diazepam (DZP, 2 mg/kg), buspirone (BUS, 3 mg/kg), mirtazapine (MIR, 10 mg/kg) and fluoxetine (FLU, 10 mg/kg) in male mice submitted to acute restraint stress, and evaluated using plus-maze discriminative avoidance task (PMDAT), which simultaneously evaluates parameters such as learning, memory and anxiety. Our results demonstrated that (1) the administration of DZP and BUS, but not FLU, promoted anxiolytic effects in animals; (2) administration mirtazapine caused sedative effect to animals; (3) in the training session, the animals treated with BUS, MIR and FLU learned the task, on the other hand DZP group showed impairment in learning; (4) in the test session, animals treated with DZP, BUS, and MIR showed deficits in relation to discrimination between the enclosed arms, aversive versus non-aversive arm, demonstrating an impairment in memory, however, animals treated with FLU showed no interference in the retrieval of this memory; (5) acute stress did not interfere in locomotor activity, anxiety, or learning on the learning task, but induced impairment in retrieval memory, and the group treated with FLU did not demonstrated this deficit of memory . These results suggest that acute administration of drugs with anxiolytic and antidepressant activity does not interfere with the learning process this aversive task, but impair its retrieval, as well as the acute restraint stress. However, the antidepressant fluoxetine was able to reverse memory deficits promoted by acute stress, which may suggest that modulation, even acutely serotonergic neurotransmission, by selectively inhibiting the reuptake of this neurotransmitter, interferes on the process of retrieval of an aversive memory

Resposta humoral de bovinos vacinados contra as toxinas botulínicas tipos C e D em diferentes faixas etárias

Foi verificada pelo teste de ELISA indireto a resposta humoral contra os toxoides botulínicos C e D em bovinos de diferentes idades. O estudo envolveu 90 animais, que foram divididos em três grupos (n = 30), de acordo com a sua faixa etária; inferior a 2 anos de idade (G1), entre 2 e 5 anos (G2) e superior a 5 anos (G3). Os grupos experimentais foram vacinados com duas doses de vacina antibotulínica bivalente (C e D) comercial, nos dias 0 e 42 após a primo-vacinação (booster). Na avaliação, quando realizada 30 dias após o booster, os animais do G3 apresentaram maior produção de anticorpos (p < 0,05) em relação aos demais grupos. Entre o G1 e G2 não houve diferença significativa na resposta humoral contra a toxina C, no entanto, contra a toxina D, os animais do G1 apresentaram maior produção de anticorpos. Todos os grupos produziram uma resposta significativa de anticorpos contra as toxinas botulínicas após a 2ª dose da vacina bivalente comercial, principalmente contra o tipo D.

Effect of Artemisia annua L. leaves essential oil and ethanol extract on behavioral assays

Artemisia annua tem sido utilizada tradicionalmente para o tratamento de malária e febre na China devido à presença do princípio ativo, artemisinina. O presente trabalho avaliou a atividade central de do óleo essencial obtido por hidrodestilação e do extrato etanólico bruto de folhas frescas de A. annua em modelo in vivo como parte de um screening farmacológico dessa espécie. Sono induzido por pentobarbital, nado forçado e o ensaio de campo aberto são modelos de estudo conhecidos para o estudo de fármacos sobre depressão induzida. A administração do óleo essencial ou extrato bruto etanólico de A. annua aumentaram o tempo de imobilidade no teste do nado forçado. Por outro lado, diminuíram outros parâmetros no campo aberto, como ambulação, exploração, o ato de lamber as patas ou se lamber. Ambos produtos aumentaram o tempo de sono induzido por pentobarbital, com o óleo essencial apresentando um efeito superior ao do extrato. Pela análise dos resultados, é possível sugerir que tanto o extrato bem como o óleo essencial podem atuar como depressores do Sistema Nervoso Central (SNC).

Aspectos clínicos e laboratoriais em ovinos submetidos a dietas com níveis elevados de enxofre com objetivo de indução de polioencefalomalácia

A polioencefalomalacia (PEM) é uma doença neurológica que acomete ruminantes e pode ser desencadeada por diversos fatores, dentre eles o consumo excessivo de enxofre. Este trabalho teve como objetivo verificar a relação entre dietas ricas em enxofre, altos níveis de gás sulfídrico ruminal e a ocorrência de polioencefalomalácia em ovinos. Foram utilizados 18 ovinos, divididos em três grupos (G1, G2 e G3) que receberam diferentes níveis de enxofre na dieta; 0,2%, 0,9% e 1,2%, respectivamente. Exames físicos (frequência cardíaca, frequência respiratória, temperatura retal e motricidade ruminal) e complementares (concentração de sulfeto de hidrogênio ruminal, hemogasometria venosa, pH do fluído ruminal, concentração de cobre sérico e hepático, tomografia computadorizada, necropsia e histopatologia) foram realizados. A temperatura retal, a hemogasometria venosa e o pH do fluido ruminal permaneceram dentro dos valores de referência para a espécie. A motricidade ruminal estava diminuída nos grupos G2 e G3 em comparação com o G1 (controle). Quanto maior a ingestão de enxofre, menores foram os níveis de cobre sérico e hepático. Valores elevados de sulfeto de hidrogênio ruminal foram detectados nos grupos G2 e G3. Nenhum animal apresentou sinais clínicos de PEM. Nos exames de tomografia computadorizada, necropsia e exame histopatológico do sistema nervoso central (SNC), não foram observadas alterações compatíveis com PEM. É provável que algum outro fator esteja associado ao excesso de enxofre na dieta para o desenvolvimento de PEM em ovinos.