Search for Salmonella spp. in ostrich productive chain of Brazilian southeast region

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

Activation of 5-HT2C receptors in the dorsal periaqueductal gray increases antinociception in mice exposed to the elevated plus-maze

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Blockade of 5-HT2 receptors in the periaqueductal grey matter (PAG) abolishes the anxiolytic-like effect of 5-HT1A receptor antagonism in the median raphe nucleus in mice

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

Blockade of fear-induced antinociception with intra-amygdala infusion of midazolam: Influence of prior test experience

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

5-HT2 receptor activation in the midbrain periaqueductal grey (PAG) reduces anxiety-like behaviour in mice

It is widely acknowledged that the indoleamine neurotransmitter serotonin (5-HT) plays a dual role in the regulation of anxiety, a role that in part depends upon neuroanatomical locus of action. Thus, whereas stimulation of 5-HT1A or 5-HT2 receptors in the limbic forebrain (amygdala, hippocampus) enhances anxiety-like responding in rodents, activation of corresponding receptor populations in the midbrain periaqueductal grey (PAG) more often than not reduce anxiety-like behaviour. The present study specifically concerns the anxiety-modulating influence of 5-HT2 receptors within the mouse PAG. Experiment 1 assessed the effects of intra-PAG infusions of the 5-HT2B/2C receptor agonist mCPP (0, 0.03, 0.1 or 0.3 nmol/0.1 mu l) on the behaviour of mice exposed to the elevated plus-maze. As mCPP acts preferentially at 5-HT2B and 5-HT2C receptors, Experiment 2 investigated its effects in animals pretreated with ketanserin, a preferential 5-HT2A/2C receptor antagonist. In both cases, test sessions were videotaped and subsequently, scored for anxiety-like behaviour (e.g., percentage of open arm entries and percentage of open arm time) as well as general locomotor activity (closed arm entries). The results of Experiment I showed that mCPP microinfusions (0.03 and 0.1 nmol) into the PAG of mice decreased behavioural indices of anxiety without significantly altering general activity measures. In Experiment 2, the anxiolytic-like profile of intra-PAG mCPP (0.03 nmol) was substantially attenuated by intra-PAG pretreatment with an intrinsically inactive dose of the preferential 5-HT2A/2C receptor antagonist, ketanserin (10 nmol/0.1 mu l). Together, these data suggest that 5HT(2C) receptor populations within the midbrain PAG play an inhibitory role in plus-maze anxiety in mice. (C) 2007 Elsevier B.V. All rights reserved.

Bases neurofisiológicas da dependência do tabaco

A maioria dos estudos pré-clínicos e clínicos aponta a nicotina como o principal agente responsável pelo desenvolvimento da dependência ao tabaco. Muitos trabalhos têm demonstrado que as bases neurais da dependência à nicotina são semelhantes àquelas das outras drogas de abuso. A nicotina induz preferência condicionada por lugar e auto-administração e, portanto, atua como reforçador positivo, esse efeito parece ser mediado pelo sistema dopaminérgico mesolímbico. A nicotina também induz à sensibilização comportamental que é provavelmente resultante de alterações da expressão gênica do núcleo acumbens induzidas pela exposição prolongada a essa substância. A suspensão do uso de nicotina resulta em síndrome de abstinência. As evidências indicam que esses sinais e sintomas sejam mediados por receptores colinérgicos nicotínicos centrais e periféricos. Outros neurotransmissores, como por exemplo a serotonina e os peptídeos opióides, também podem estar envolvidos na mediação da dependência e síndrome de abstinência à nicotina. A revisão da literatura mostra a complexidade dos efeitos da nicotina no organismo. A integração entre as abordagens comportamental, neuroquímica e molecular possibilitará a compreensão dos mecanismos neurais da dependência ao tabaco e fornecerá as bases para o desenvolvimento racional de agentes terapêuticos que possam ser utilizados para o tratamento da dependência e síndrome de abstinência ao tabaco.

Maternal separation stress in male mice: long-term increases in alcohol intake

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Descrição de dieta purificada para indução de quadro de desnutrição protéica em ratos

No presente trabalho é descrita a composição de dieta hipoprotéica (6% de proteína) purificada para indução de quadro de desnutrição em roedores. A referida dieta foi padronizada em laboratório a partir de modificação da AIN-93 (documento do American Institute of Nutrition que estabelece os padrões nutricionais para roedores de laboratório), visando a obtenção de animais desnutridos para estudar as alterações metabólicas decorrentes da desnutrição protéica associada a situações como exercício físico, gestação e diabetes. A dieta em questão contém os seguintes componentes (g/ kg): amido de milho (480), caseína (71,5), dextrina de milho (159), sacarose (121), óleo de soja (70), microcelulose (50), mistura mineral AIN-93-G-MX (35), mistura de vitaminas AIN-93-G-VX, (10), L-cistina (1), cloridrato de colina (2,5). Ratos alimentados cronicamente com a dieta apresentaram sinais comumente presentes na desnutrição protéica humana e de animais de laboratório: redução do ganho de peso, hipoproteinemia, hipoalbuminemia, elevação dos ácidos graxos livres séricos e do glicogênio hepático.

The adaptive compensations in endocrine pancreas from glucocorticoid-treated rats are reversible after the interruption of treatment

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

Increased pancreatic islet mass is accompanied by activation of the insulin receptor substrate-2/serine-threonine kinase pathway and augmented cyclin D(2) protein levels in insulin-resistant rats

It is well known that glucocorticoids induce peripheral insulin resistance in rodents and humans. Here, we investigated the structural and ultrastructural modifications, as well as the proteins involved in beta-cell function and proliferation, in islets from insulin-resistant rats. Adult male Wistar rats were made insulin resistant by daily administration of dexamethasone (DEX; 1mg/kg, i.p.) for five consecutive days, whilst control (CTL) rats received saline alone. Structure analyses showed a marked hypertrophy of DEX islets with an increase of 1.7-fold in islet mass and of 1.6-fold in islet density compared with CTL islets (P < 0.05). Ultrastructural evaluation of islets revealed an increased amount of secreting organelles, such as endoplasmic reticulum and Golgi apparatus in DEX islets. Mitotic figures were observed in DEX islets at structural and ultrastructural levels. Beta-cell proliferation, evaluated at the immunohistochemical level using anti-PCNA (proliferating cell nuclear antigen), showed an increase in pancreatic beta-cell proliferation of 6.4-fold in DEX islets compared with CTL islets (P < 0.0001). Increases in insulin receptor substrate-2 (IRS-2), phosphorylated-serine-threonine kinase AKT (p-AKT), cyclin D(2) and a decrease in retinoblastoma protein (pRb) levels were observed in DEX islets compared with CTL islets (P < 0.05). Therefore, during the development of insulin resistance, the endocrine pancreas adapts itself increasing beta-cell mass and proliferation, resulting in an amelioration of the functions. The potential mechanisms that underlie these events involve the activation of the IRS-2/AKT pathway and activation of the cell cycle, mediated by cyclin D(2). These adaptations permit the maintenance of glycaemia at near-physiological ranges.

A cafeína exerce efeitos positivos sobre a memória tipo episódica em ratos adultos sem influenciar a sobrevivência neural no giro dentado

The caffeine is a mild psychostimulant that has positive cognitive effects at low doses, while promotes detrimental effects on these processes at higher doses. The episodic-like memory can be evaluated in rodents through hippocampus-dependent tasks. The dentate gyrus is a hippocampal subregion in which neurogenesis occurs in adults, and it is believed that this process is related to the function of patterns separation, such as the identification of spatial and temporal patterns when discriminating events. Furthermore, neurogenesis is influenced spatial and contextual learning tasks. Our goal was to evaluate the performance of male Wistar rats in episodic-like tasks after acute or chronic caffeine treatment (15mg/kg or 30mg/kg). Moreover, we assessed the chronic effect of the caffeine treatment, as well as the influence of the hippocampus-dependent learning tasks, on the survival of new-born neurons at the beginning of treatment. For this purpose, we used BrdU to label the new cells generated in the dentate gyrus. Regarding the acute treatment, we found that the saline group presented a tendency to have better spatial and temporal discrimination than caffeine groups. The chronic caffeine group 15 mg/kg (low dose) showed the best discrimination of the temporal aspect of episodic-like memory, whereas the chronic caffeine group 30mg/kg (high dose) was able to discriminate temporal order, only in a condition of greater difficulty. Assessment of neurogenesis using immunohistochemistry for evaluating survival of new-born neurons generated in the dentate gyrus revealed no difference among groups of chronic treatment. Thus, the positive mnemonic effects of the chronic caffeine treatment were not related to neuronal survival. However, another plastic mechanism could explain the positive mnemonic effect, given that there was no improvement in the acute caffeine groups

Diferenças funcionais das regiões hipocampais na formação da memória do tipo o quê", "quando" e "onde" em ratos

Episodic memory refers to the recollection of what, where and when a specific event occurred. Hippocampus is a key structure in this type of memory. Computational models suggest that the dentate gyrus (DG) and the CA3 hippocampal subregions are involved in pattern separation and the rapid acquisition of episodic memories, while CA1 is involved in memory consolidation. However there are few studies with animal models that access simultaneously the aspects ‗what-where-when . Recently, an object recognition episodic-like memory task in rodents was proposed. This task consists of two sample trials and a test phase. In sample trial one, the rat is exposed to four copies of an object. In sample trial two, one hour later, the rat is exposed to four copies of a different object. In the test phase, 1 h later, two copies of each of the objects previously used are presented. One copy of the object used in sample trial one is located in a different place, and therefore it is expected to be the most explored object.However, the short retention delay of the task narrows its applications. This study verifies if this task can be evoked after 24h and whether the pharmacological inactivation of the DG/CA3 and CA1 subregions could differentially impair the acquisition of the task described. Validation of the task with a longer interval (24h) was accomplished (animals showed spatiotemporal object discrimination and scopolamine (1 mg/kg, ip) injected pos-training impaired performance). Afterwards, the GABA agonist muscimol, (0,250 μg/μl; volume = 0,5 μl) or saline were injected in the hippocampal subregions fifteen minutes before training. Pre-training inactivation of the DG/CA3 subregions impaired the spatial discrimination of the objects (‗where ), while the temporal discrimination (‗when ) was preserved. Rats treated with muscimol in the CA1 subregion explored all the objects equally well, irrespective of place or presentation time. Our results corroborate the computational models that postulate a role for DG/CA3 in spatial pattern separation, and a role for CA1 in the consolidation process of different mnemonic episodes

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

Expressão de fos após pulso de escuro no núcleo pré- geniculado do tálamo do sagui (Callithrix jacchus)

The pregeniculate nucleus (PGN) of the primate s thalamus is an agglomerate neuronal having a cap shaped located dorsomedially to the main relay visual information to the cerebral cortex, the dorsal lateral geniculate nucleus (GLD). Several cytoarchitectonic, neurochemical and retinal projections studies have pointed PGN as a structure homologous to intergeniculate leaflet (IGL) of rodents. The IGL receives retinal terminals and appears to be involved in the integration of photic and non-photic information relaying them, through geniculo-hypothalamic tract (TGH), to the main circadian oscillator in mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus. Thus, the IGL participates in the control of the biological rhythm by modulating the activity of the SCN. Pharmacological and IGL injury studies conclude that it is critical in the processing of non-photic information which is transmitted to the SCN. Other studies have found that especially neurons immunoreactive to neuropeptide Y (NPY) respond to this type of stimulation, determined by its colocation with the FOS protein. Has not been determined if the PGN responds, expressing the FOS protein, to the non-photic stimulus nor the neurochemical nature of these cells. Thus, we apply a dark pulse in the specifics circadian phases and analyze the pattern of expression of FOS protein in PGN of the marmoset (Callithrix jacchus). We found that in all animals analyzed the FOS expression was higher in the experimental than in the control group. There was a higher expression of FOS when the dark pulse was applied during the subjective day between the groups. Still, a subregion of the PGN, known by immunoreactive to NPY, had a greater number of FOS-positive cells in relation to his other just close dorsal region. Our data corroborate the theory that the PGN and IGL are homologous structures that were anatomically modified during the evolutionary process, but kept its main neurochemical and functional characteristics. However, injury and hodological studies are still needed for a more accurate conclusion

Efeitos da senescência no núcleo supraquiasmático do sagui (Callithrix Jacchus): plasticidade morfológica e neuroquímica

The circadian timing system (CTS) is responsible for the generation and synchronization and the suprachiasmatic nucleus (SCN) of the hypothalamus has been described as the major circadian pacemaker in many mammalian species. The internal temporal organization managed by SCN is disturbed with aging bringing many pathological disorders that range from loss of complex cognitive performance to simple physiological functions. Therefore, our aim was perform a comparative study of the morphological aspects and neurochemical composition in the SCN of marmosets (Callithrix jacchus) adults and older using immunohistochemical techniques. We found morphometric and neurochemical changes in th SCN o folder animals in comparison to adults, among these a possible decreased in retinal projection to the SCN of older animals, found through a decline in CTB immunostaining, which can occur due atrophy and/or decreasing of fibers from the retinohypothalamic tract (RHT). The Klüver-Barrera histological technique strongly suggests a decrease in those fibers from RHT. Also, by means of a morphometric study, it is found a atrophy and numerical decline of neurons in SCN of aged animals, investigated by Nissl technique, and immunostaining with NeuN and calbindin. Relative optical density (ROD) analysis were used to evaluate the expression of some neurochemical components in SCN, such as GFAP expression, which was increased in older, result that indirectly reinforces that morphological changes occurs due the aging; the vasoactive intestinal polipeptide (VIP) showed no expression alteration in SCN of older animals; the serotonin (5-HT) was descreased in the dorsomedial portion of the SCN, and neurpeptide Y (NPY) apparently also decrease due to the increase of age. Many of these modifications were seen in other animals, such as rodents, human primates and non-human primates. These data about marmoset comes to add new information of the effect of aging on structures responsibles for the circadian rhytmicity, and that some behavioral changes controlled by th SCN, and founded in aged animals, may be caused by these morphological and neurochemical changes. Although some results have been quantitatively negative, qualitatively all analysis show significant change comparing adult and older animals, perhaps due to a low sampling number. In conclusion, the marmoset presents several morphological and neurochemical changes in the SCN of aged animals compared to adults, which may result in behavioral changes that favor pathology aging related