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

Avaliação comportamental e neuroquímica de ratos em dessincronização forçada: possíveis implicações para um modelo animal de oscilações no humor

Bipolar disorder has been growing in several countries. It is a disease with high mortality and has been responsible by the social isolation of the patients. Bipolar patients have alterations in circadian timing system, showing a phase shift in various physiological variables. There are several arguments demonstrating alterations in circadian rhythms may be part of the bipolar disorder pathophysiology. Given the necessity for further elucidation, the goal of this study was to validate the forced desynchronization protocol as an animal model for bipolar disorder. To do this, Wistar rats were submitted to a forced desynchronization protocol which consists in a symmetrical light dark cycle with 22h. Under this protocol, rats dissociate the locomotor activity rhythm into two components: one synchronized to the light / dark cycle with 22h, and another component with period longer than 24 hours following the animal endogenous period. These rhythms with different periods sometimes there is coincidence, which we named CAP (Coincidence Active Phase) and the opposite phase, non-coincidence, called NCAP (Non-Concidence Active Phase). The hypothesis is that in CAP animals present a mania-like behavior and animals in NCAP depressive-like behavior. We found some evidence described in detail throughout this thesis. In sum, the animals under forced desynchronization protocol were more stressed, showed an increase in stereotypic behaviors such as grooming and reduction in other behaviors such as risk assessment and vertical exploration when compared to the control group. The CAP animals showed increased locomotor activity, especially during the dark phase when compared to controls (rats under T24) and less depressive behavior in the forced swim test. The animals in NCAP showed a higher anxiety in elevated plus maze, but they don t have ahnedonia. The animals under dissociation have more labeled 5HT1A cells at the amygdala area, which appoint that they have more amygdala inhibition. Taking these data together, we could partially validated the forced desynchronization protocol as an animal model for mood oscillations

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

Antidepressivos modificam a extinção de uma memória aversiva em ratas

Treatment of major depression, posttraumatic stress disorder and other psychopathologies with antidepressants can be associated with improvement of the cognitive deficits related to these disorders. Although the mechanisms of these effects are not completely elucidated, alterations in extinction of aversive memories are believed to be present in these psychopathologies. Moreover, researches with laboratory animals usually focus on male subjects, and we have recently verified that extinction of an aversive task is reduced in female rats when compared to males. In the present study, female rats were long-term treated with clinically used antidepressants (fluoxetine, nortriptyline or mirtazapine) and tested in the plus-maze discriminative avoidance and forced swimming tests in order to evaluate learning, memory, extinction, anxiety and depression-related behaviors. All groups learned the task, but learning was somewhat faster in nortriptyline and mirtazapine-treated animals . Task retrieval was also showed by all experimental groups. Chronic treatment with fluoxetine, but not with the other antidepressants, increased extinction of the discriminative task. In the forced swimming test, animals treated with fluoxetine and mirtazapine showed decreased immobility duration. In conclusion, antidepressants interfere with learning and female rats treated with fluoxetine presented increased extinction of the aversive memory task. On the other hand, both fluoxetine and mirtazapine were effective in the forced swimming test, suggesting dissociation between the antidepressant effects and the extinction of aversive memories

Avaliação dos efeitos do biperideno, diazepam e neuropeptídeos S sobre a memória e a ansiedade na tarefa do labirinto em T elevado em camundongos

Anxiety is an emotional phenomenon, and normally it is interpreted as an adaptative behavior front to adversities. In its pathological form, anxiety can severely affect aspects related to the personal and professional life. Studies have shown a close relationship between anxiety disorders and aversive memory processing. Considering that the pharmacotherapy of anxiety disorders is still limited, innovative anxiolytic agents are needed. In this regard, neuropeptides systems are interesting therapeutic targets to the treatment of psychopathologies. Neuropeptide S (NPS), a 20-aminoacid peptide, is the endogenous ligand of a G-protein coupled receptor (NPSR), which has been reported to evoke hyperlocomotion, awakefull states, besides anxiolysis and memory improvements in rodents. This study aimed to investigate the effects of biperiden (BPR; an amnesic drug), diazepam (DZP; an anxiolytic drug) and NPS at three distinct times: pre-training, post-training, and pre-test, in order to assess anxiety and memory process in the same animal model. The elevated Tmaze (ETM) is an apparatus derived from the elevated plus-maze test, which consists of one enclosed and two open arms. The procedure is based on the avoidance of open spaces learned during training session, in which mice were exposed to the enclosed arm as many times as needed to stay 300 s. In the test session, memory is assessed by re-exposing the mouse to the enclosed arm and the latency to enter an open arm was recorded. When injected pre-training, BPR (1 mg/kg) impaired learning and memory processing; DZP (1 and 2 mg/kg) evoked anxiolysis, but only at the dose of 2 mg/kg impaired memory; and NPS 0.1 nmol induced anxiolysis without affecting memory. Post-training injection of DZP (2 mg/kg) or BPR (1 and 3 mg/kg) did not affect memory consolidation, while the post-trainning administration of NPS 1 nmol, but not 0.1 nmol, improved memory in mice. Indeed, pre-trainning administration of NPS 1 nmol did not prevent memory impairment elicited by BPR (2 mg/kg, injected before training). In the open field test, BPR 1 mg/kg and NPS 1 nmol induced hyperlocomotion in mice. In conclusion, the proposed ETM task is practical for the detection of the anxiolytic and amnesic effects of drugs. The anxiolytic and memory enhancement effects of NPS were detected in the ETM task, and reinforce the role of NPS system as an interesting therapeutic target to the treatment of anxiety disorders

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.

Efeitos da estimulação ambiental sobre os aspectos motores, cognitivos e neuronais em um modelo farmacológico progressivo da doença de Parkinson

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Attitude stability of artificial satellites subject to gravity gradient torque

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Participação da neurotransmissão dopaminergica no efeito hiperlocomotor do neuropeptideo S

Neuropeptide S (NPS) is an endogenous 20-aminoacid peptide which binds a G protein-coupled receptor named NPSR. This peptidergic system is involved in the modulation of several biological functions, such as locomotion, anxiety, nociception, food intake and motivational behaviors. Studies have shown the participation of NPSR receptors in mediating the hyperlocomotor effects of NPS. A growing body of evidence suggests the participation of adenosinergic, dopaminergic and CRF systems on the hyperlocomotor effects of NPS. Considering that little is known about the role of dopaminergic system in mediating NPS-induced hyperlocomotion, the present study aims to investigate the locomotor actions of intracerebroventricular (icv) NPS in mice pretreated with α-metil-p-tirosine (AMPT, inhibitor of dopamine synthesis), reserpine (inhibitor of dopamine vesicle storage) or sulpiride (D2 receptor antagonist) in the open field test. A distinct group of animals received the same pretreatments described above (AMPT, reserpine or sulpiride) and the hyperlocomotor effects of methylphenidate (dopamine reuptake inhibitor) were investigated in the open field. NPS and methylphenidate increased the mouse locomotor activity. AMPT per se did not change the locomotion of the animals, but it partially reduced the hyperlocomotion of methylphenidate. The pretreatment with AMPT did not affect the psychostimulant effects of NPS. Both reserpine and sulpiride inhibited the stimulatory actions of NPS and methylphenidate. These findings show that the hyperlocomotor effects of methylphenidate, but not NPS, were affected by the pretreatment with AMPT. Furthermore, methylphenidate- and NPS-induced hyperlocomotion was impaired by reserpine and sulpiride pretreatments. Together, data suggests that NPS can increase locomotion even when the synthesis of catecholamines was impaired. Additionally, the hyperlocomotor effects of NPS and methylphenidate depend on monoamines vesicular storaged, mainly dopamine, and on the activation of D2 receptors. The psychostimulant effects of NPS via activation of dopaminergic system display clinical significance on the treatment of diseases which involves dopaminergic pathways, such as Parkinson s disease and drug addiction

Study of Stability of Rotational Motion of Spacecraft with Canonical Variables

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação das características de afetividade em crianças e jovens com síndrome de down

This work presents the processes and the results of a research concerning the affectivity in children suffering from the Down´s Syndrome (DS). The relevance of the study is justified due to the need of the development of researches, in the area of psychological evaluation of people who suffers from Down´s Syndrome (DS), that are backed by the use of appropriate instruments for such purpose. The thematic discussed focuses the characteristics of the affectivity of children suffering from Down´s Syndrome. Affectivity, conceptually, is considered a wide phenomenon, including several aspects such as emotions, passions, anxiety, anguish, sadness, happiness and even the pleasure sensations and pain. The general objective of the study consisted of investigating the manifestation of the affectivity in children and young with Down´s Syndrome and the parents´ and educators´ perception concerning the expression of the affectivity in the behavior and in the social activities. The specific objectives were: to identify the parents' perceptions about the several manifestations of indicative behaviors of affectivity; to verify in the social atmosphere, outside home, through the teachers' perception, the several forms and intensities of the expression of the affectivity; and, to make possible the use of the technique of Zulliger (Z-test) in people with Down´s Syndrome. 70 (seventy) children and young with Down´s Syndrome participated in the research, in the age group from 04 to 26 years old, which are attended by Institutions of Paraíba and of Rio Grande do Norte. The instruments used were two questionnaires, applied with the parents and teachers, and the projective technique, Z-test, applied, individually, with the children and young with Down´s Syndrome. For analysis of the data of the questionnaires, the program Trideux-Mots was used, with the intention of selecting the main outstanding words for the parents and teachers concerning the expression of the children's affectivity and young with Down´s Syndrome. For so much, it was organized a database that was processed by that program and, soon after, interpreted through the Factorial Analysis by Correspondence (AFC), looking for to clear the modalities of presented answers in an organized way, through a graph. The data of the Z-test were analyzed, taking in consideration the need to characterize the aspects of the affectivity and the elaboration of specific norms for this sample type, through normalized scores. In agreement with the data presented by Tri-deux-Mots, it was observed that in the affective behavior and in the relationship with the other, home and in the school, the children and young with Down´s Syndrome they express your affectivity through positive and negative characteristics, in the same way that any other child that doesn't have to syndrome. The Z-test made possible initial elements to work with that population, however it is necessary that grow other researches with the intention of investigating the reason of the answers they present not the specific categories that you/they are related to the affectivity, since it was well-known the diversity of affective characteristics presented by the researched group

O oncologista clínico diante da morte: implicações para a produção do cuidado

It is undeniable that all the extraordinary technological advances in contemporary society have increased the severe patients expectation and quality of life, especially cancer patients. On the other hand, it is easily verifiable by many researches that it was not possible to advance in the same proportion in caring for the human experience of death. Much is said about the anguish of a man facing death, of cancer patients in terminal stage, about their families, and very little about the feelings, anxieties and ways of coping with the medical professional who deals with this situation, specifically the clinical oncologist. Little is known about the experience of the doctor who has learned to take death as an enemy to be defeated, and increasingly is compelled to live at length with his advertisement. However, we started to watch in recent years a growing interest of researchers in this issue. This study seeks to add to this interest in order to understand the experience of clinical oncologists that accompany dying patients, the meanings they attach to death, ways of coping and the implications for providing care. This is a qualitative study in which was used as a tool for data collection an in-depth interview with the projective using script and scenes. Gadameriana Hermeneutics was used for analysis and interpretation of narratives. The subjects were 10 clinical oncologists who work at two institutions from cancer treatments in the state of Rio Grande do Norte, chosen from a variation in the time working in the specialty (minimum of one year, even old ones). However, you can bring some initial results for the dialogue. It was found that the death is still a topic that causes many difficulties in the daily lives of these professionals, the choice for oncology involves dealing with death without preparation in medical education; being close to the patient in the final moment, supporting the family, coping with own pain of loss and the inability to heal. These are central elements of the narratives. We also have investment in medical training and continuing education in setting up a demand that permeates the discourse of participants. Being able to listen to the subjective world of clinical oncologists will support the work not only for them as other professionals who deal with patients with advanced cancer, providing evidence to understand to what extent the meanings attributed to its know-how before patients on the verge of death interfere with the production of care and allow identify coping strategies in everyday life of these professionals that hinder or facilitate coping with death, promote or preclude the care with others and with themselves. It is hoped that research can contribute to the field of knowledge about the know-how in clinical oncology and their terminal-care-death oncologist-patient relationships, bringing runways capable of promoting a better quality of care in the production of all involved in this process: professionals, patients and families

Os agentes funerários e a morte: o cuidado presente diante da vida ausente

The present time is marked by the art of escape from death, which has become synonymous with failure, its exposure has become intolerable and the care of the dead body were assigned to third parties who market this practice through services and products that shape the market undertaker. In this context, in which death is an object of study, has arisen funeral officers, as professionals dealing with a dead body, with the pain of relatives and their reactions, often being the first to have contact with the death scene. As professionals in the health area, the morticians also deal with death. The first attempt to prevent the arrival of death, funeral officers already has begun their work routine from there. Death and its surrounding part of their profession. What about those professionals whose work demands as a feared and denied by society? This study aims to understand the intents, meanings and implications for the mortician to deal with death in their daily work in order to focus renewed attention to the care of these professionals. To this end, it was carried out a qualitative research grounded in the theoretical framework of Gadamerian hermeneutics for production and interpretation of narratives. It was used two methodological strategies for data collection: in-depth interview with script and workshop with the use of "scenes". Research participants were nine morticians funeral of two funeral agencies of the city of Natal. It was possible to detect the presence of the social imaginary of interdiction on the theme of death from living with feelings of his presence daily, from the need of respondents to naturalize their contacts with death, a requirement of their office to deal with the difficulties of manipulating body fluids and odors, sometimes in a state of decomposition; allied to wishes to achieve the goal of delivering to family-customers a "embellished" body for the final farewell. Being a mortician, in addition to not being a professional motivation, involves facing difficulties related to heavy routine work, low salaries, unprofitable work materials and equipments, besides having to deal with the social gaze that devalues the profession. In turn, they also deal with the pain coming especially from contact with family members, either when they are targets of these feelings of anger, whether they identify with the pain of the bereaved ones. On the other hand, when the recognition and gratitude of the families occur, they find meaning and beauty in their profession of caring for the dead body. The present study by giving voice to morticians has become possible to understand better their profession, the pain that surrounds and care needs of these workers. Finally, it has argued that the mortician may be recognized as a care professional for the way exercising caution with the dead body and their families.

Avaliação do potencial anticorrosivo de tiossemicarbazonas solubilizadas em sistemas microemulsionados

In this work thiosemicarbazones [4-N-cinnamoyl-thiosemicarbazone (CTSC), 4-N-(2'-methoxycinnamoyl)-thiosemicarbazone (MCTSC), and 4-N-(4'-hydroxy-3'-methoxybenzoyl)-thiosemicarbazone (HMBTSC)] were solubilized in an microemulsion system (ME_OCS) which is rich in aqueous phase (O/W system). The system ME_OCS was obtained with saponified coconut oil (OCS) as (surfactant), butanol (cosurfactant), and kerosene as oil phase (Fo), using 40% of C/T (cosurfactant/surfactant), 5% of Fo and 55% of aqueous phase. The microemulsions systems CTSC_ME_OCS, MCTSC_ME_OCS and HMBTSC_ME_OCS effectiveness on a AISI 1020 carbon steel corrosion inhibition process were evaluated in a saline solution (NaCl 0.5%), using a galavostatic method. The tested thiosemicarbazones (TSC) showed highest inhibitors effects (85.7% for CTSC_ME_OCS, 84.0% for MCTSC_ME_OCS, and 83.3% HMBTSC_ME_OCS) at lower concentrations [0.19% of CTSC, 0.07% (MCTSC), and 0.26% (HMBTSC)]. Comparatively, the surfactant OCS (solubilized in H2O) as well as the system ME_OCS showed lower efficacy [71% for OCS (at 0.20 - 0.25% of concentration) and 74% for ME_OCS (at 0.5% of concentration)]. Since the microemulsion systems ME_OCS showed satisfactory interfacial adsorption, the greatest inhibitory effect of those TSC_ME_OCS systems could be correlated to both chemical composition of each tested TSC (which is rich in heteroatoms and aromatic ring) and also the presence of the surfactant OCS

Evidence that the Ceratobasidium-like white-thread blight and black rot fungal pathogens from persimmon and tea crops in the Brazilian Atlantic Forest agroecosystem are two distinct phylospecies

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