Expressão de zif-268 durante a aquisição, evocação e extinção de uma memória aversiva

In the behavioral paradigm of discriminative avoidance task, both short and long-term memories have been extensively investigated with behavioral and pharmacological approaches. The aim of the present study was to evaluate, using the abovementioned model, the hippocampal expression of zif-268 - a calcium-dependent immediate early gene involved with synaptic plasticity process - throughout several steps of memory formation, such as acquisition, evocation and extiction. The behavioral apparatus consisted of a modified elevaated plus-maze, with their enclosed arms disposed in "L". A pre-exposure to the maze was made with the animal using all arms enclosed, for 30 minutes, followed by training and test, during 10 minutes each. The between sections interval was 24h. During training, aversive stimuli (bright light and loud noise) were actived whenever the animals entered one of the enclosed armas (aversive arm). Memory acquisiton, retention and extinction were evaluated by the percentage of the total time spent exploring the aversive arm. The parameters evaluated (time spent in the arms and total distance traveled) were estimated with an animal tracking software (Anymaze, Stoelting, USA). Learning during training was estimated by the decrease of the time spent exploring the aversive arm. One hour after the beginning of each section, animals were anaesthetized with sodium-thiopental (i.p.) and perfused with 0.9% heparinized saline solution followed by 4% paraformaldehyde. Brains were cryoprotected with 20% sucrose, separeted in three blocks and frozen. The middle block, containing the hippocampus, was sectioned at 20 micro meters in the coronal plane and the resutant sections were submitted to zif-268 immunohistochemistry. Our results show an increased expression of zif-268 in the dentate gyrus (DG) during the evocation and extinction stages. There is a distinct participation of the DG during the memory evocation, but not during its acquisition. Inaddition, all hippocampal regions (CA1, CA3 and DG) presented an increased zif-268 expression during the process of extinction.

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.

Os núcleos dopaminérgicos do mesencéfalo do mocó (kerodon rupestris): caracterização citoarquitetônica e por imunoistoquímica para tirosina-hidroxilase

The 3-hydroxytyramine/dopamine (DA) is a monoamine of catecholamineric group and consists in the progenitor substantia of synthesis of noradrenaline and adrenaline, having the enzyme tyrosine hydroxylase as a regulator of this process. Nuclei of midbrain expressing DA are the retrorubral field (RRF, A8 group), the substantia nigra pars compacta (SNc, A9 group) and the ventral tegmental area (VTA, A10 group). These nuclei are involved in three complex circuitry called mesostriatal, mesocortical and mesolimbic, which are related directly with various behavioral manifestations such as motor control, reward signaling in behavioural learning, motivation and pathological manifestations of Parkinson s disease and schizophrenia. The aim of this study was describe the morphology of midbrain dopaminergic neurons (A8, A9 and A10) of the rock cavy (Kerodon rupestris), a rodent belonging to the family Caviidae typical of the Brazilian Northeast, which is being adopted as a model for neuroanatomical studies in laboratory of neuroanatomy of the Federal University of Rio Grande do Norte. Coronal sections of brains of the rock cavies were submitted to staining by Nissl s method and immunohistochemistry against tyrosine hydroxylase. The nuclear organization of the midbrain dopaminergic nuclei of the rock cavy is very similar to that found in other animals of the order Rodentia, except by the presence of the tail of substantia nigra, which was found only in the studied species. We concluded that the midbrain dopaminergic nuclei are phylogenetically stable among species, but we think to be it necessary to expand the studies about the particularity found the rock cavy, investigating its occurrence in other species of rodents or investigating its functional relevance

Participação do circuito dopaminérgico nas alterações do comportamento de medo inato de camundongos infectados pelo Toxoplasma gondii

The protozoan parasite Toxoplasma gondii transforms the innate aversion of rats for cat urine into a fatal attraction, that increases the likelihood of the parasite completing its life cycle in the cat s intestine. The neural circuits implicated in innate fear, anxiety, and learned fear all overlap considerably, raising the possibility, that T. gondii may disrupt all of these nonspecifically. In this study, we evaluated immunoreactivity for tyrosine hydroxylase (TH) in areas associated with innate fear of infected male swiss mice. The latent Toxoplasma infection converted the aversion of mice to feline odors into attraction. This loss of fear is remarkably specific, as demonstrated by Vyas et al (2007), because infection did not diminish learned fear, anxiety-like behavior, olfaction, or nonaversive learning. However, the neurochemical mechanism related to alterations in innate fear due to T. gondii infection remains poorly studied. 20 mice were inoculated with bradyzoites (25 cysts) from a Toxoplasma gondii (Me-49 strain). The brains were removed after 60 days, sectioned and processed for TH immunohistochemistry. The correlation between the amount of cysts per area and the densitometric analysis of neurotransmitter reactivity was low in the areas implicated in innate fear of infected animals, when comparated with noninfected controls

Efeitos do tratamento com lítio na memória aversiva, comportamentos relacionados à ansiedade e depressão e na expressão de BDNF em ratos

Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness characterized by mood oscillations between mania and depression. However, studies have demonstrated that this drug might influence mnemonic process due to its neuroprotector, antiapoptotic and neurogenic effects. The use of Li in the treatment of cognitive deficits caused by brain injury or neurodegenerative disorders have been widely studied, and this drug shows to be effective in preventing or even alleviating the memory impairment. The effects of Li on anxiety and depression are controversial and the relationship of the effects of lithium on memory, anxiety and depression remain unknown. In this context, this study aims to: evaluate the effects of acute and chronic administration of lithium carbonate in aversive memory and anxiety, simultaneously, using the plus maze discriminative avoidance task (PMDAT); test the antidepressant effect of the drug through the forced swimming test (FS) and analyze brainderived neurotrophic factor (BDNF) expression in structures related to memory and emotion. To evaluation of the acute effects, male Wistar rats were submitted to i.p. administration of lithium carbonate (50, 100 or 200 mg/kg) one hour before the training session (PMDAT) or lithium carbonate (50 or 100 mg/kg) one hour before the test session (FS). To evaluation of the chronic effects, the doses administered were 50 or 100 mg/kg or vehicle once a day for 21 days before the beginning of behavioral tasks (PMDAT and FS). Afterwards, the animals were euthanized and their brains removed and submitted to immunohistochemistry procedure to quantify BDNF. The animals that received acute treatment with 100 and 200 mg/kg of Li did not discriminated between the enclosed arms (aversive and non-aversive) in the training session of PMDAT, showing that these animal did not learned the task. This lack of discrimination was also observed in the test session, showing that the animals did not recall the aversive task. We also observed an increased exploration of the open arms of these same groups, indicating an anxiolytic effect. The same groups showed a reduction of locomotor activity, however, this effect does not seem to be related with the anxiolytic effect of the drug. Chronic treatment with Li did not promote alterations on learning or memory processes. Nevertheless, we observed a reduction of open arms exploration by animals treated with 50 mg/kg when compared to the other groups, showing an anxiogenic effect caused by this dose. This effect it is not related to locomotor alterations since there were no alterations in these parameters. Both acute and chronic treatment were ineffective in the FS. Chronic treatment with lithium was not able to modify BDNF expression in hippocampus, amygdala and pre-frontal cortex. These results suggest that acute administration of lithium promote impairments on learning in an aversive task, blocking the occurrence of memory consolidation and retrieval. The reduction of anxiety following acute treatment may have prevented the learning of the aversive task, as it has been found that optimum levels of anxiety are necessary for the occurrence of learning with emotional context. With continued, treatment the animals recover the ability to learn and recall the task. Indeed, they do not show differences in relation to control group, and the lack of alterations on BDNF expression corroborates this result. Possibly, the regimen of treatment used was not able to promote cognitive improvement. Li showed acute anxiolytic effect, however chronic administration 4 promoted the opposite effect. More studies are necessary to clarify the potential beneficial effect of Li on aversive memory

Organização nuclear do sistema serotonérgico no encéfalo de morcegos Artibeus planirostris

Serotonin or 5-hydroxytryptamine (5-HT) is a substance found in many tissues of the body, including the nervous system acting as a neurotransmitter. Within the neuro-axis, the location of the majority of the 5-HT neurons is superimposed with raphe nuclei of the brain stem, in the median line or its vicinity, so that neuronal 5-HT can be considered a marker of the raphe nuclei. Serotonergic neurons are projected to almost all areas of the brain. Studies show the participation of serotonin in regulating the temperature, feeding behavior, sexual behavior, biological rhythms, sleep, locomotor function, learning, among others. The anatomy of these groups has been revised in many species, including mouse, rabbit, cat and primates, but never before in a bat species from South America. This study aimed to characterize the serotonergic clusters in the brain of the bat Artibeus planirostris through immunohistochemistry for serotonin. Seven adult bat males of Artibeus planirostris species (Microchiroptera, Mammalia) were used in this study. The animals were anesthetized, transcardially perfused and their brains were removed. Coronal sections of the frozen brain of bats were obtained in sliding microtome and subjected to immunohistochemistry for 5-HT. Delimit the caudal linear (CLi), dorsal (DR), median (MnR), paramedian (PMnR), pontine (PNR), magnus (MgR), pallidus (RPA) and obscurus (ROb) raphe nucleus, in addition to the groups B9 and rostral and caudal ventrolateral (RVL/CVL). The serotonergic groups of this kind of cheiroptera present morphology and cytoarchitecture relatively similar to that described in rodents and primates, confirming the phylogenetic stability of these cell clusters.