Efeitos da adição de carga no treino de marcha na esteira em indivíduos com Doença de Parkinson: ensaio clínico controlado randomizado

Introduction: The intrinsic gait disorders in individuals with Parkinson's disease (PD) are one of the most disabling motor symptoms. Among the therapeutic approaches used in attempts to improve the motor function, especially the gait pattern of individuals, stands out the treadmill gait training associated with the addition of load. However, there are few findings that elucidate the benefits arising from such practice. Objective: To assess the effects of adding load on the treadmill gait training in individuals with PD. Material and Methods: A controlled, randomized and blinded clinical trial, was performed with a sample of 27 individuals (18 men and 9 women) with PD, randomly assigned to three experimental conditions, namely: treadmill gait training (n=9), treadmill gait training associated with addition of 5% load (n=9) and treadmill gait training associated with addition of 10% load (n=9). All volunteers were assessed, during phase on of Parkinson's medication, regarding to demographic, clinical and anthropometric (identification form) data, level of disability (Hoehn and Yahr Modified Scale), cognitive function (Mini Mental State Examination), clinical functional - in those areas activity of daily living and motor examination (Unified Parkinson's Disease Rating Scale - UPDRS) and gait cinematic analysis was performed through Qualisys Motion Capture System®. The intervention protocol consisted of gait training in a period of 4 consecutive weeks, with three weekly sessions, lasting 30 minutes each. The post-intervention assessment occurred the next day after the last training session, which was performed cinematic analysis of gait and the UPDRS. Data analysis was performed using the software Statistical Package for Social Sciences® (SPSS) 17.0. Results: The age of volunteers ranged from 41 to 75 years old (62,26 ± 9,07) and the time of clinical diagnosis of PD between 2 to 9 years (4,56 ± 2,42). There was a reduction regarding the score from motor exam domain (p=0,005), only when training with the addition of a 5% load. As for the space-time variables there was no significant difference between groups (p>0,120); however, the training with addition of 5% load presented the following changes: increase in stride length (p=0,028), in step length (p=0,006), in time balance of the most affected member (p=0,006) and reduction in support time of the referred member (p=0,007). Regarding angular variables significant differences between groups submitted to treadmill gait training without addition load and with 5% of load were observed in angle of the ankle at initial contact (p=0,019), in plantar flexion at toe-off (p=0,003) and in the maximum dorsiflexion in swing (p=0,005). While within groups, there was a reduction in amplitude of motion of the ankle (p=0,048), the only workout on the treadmill. Conclusion: The treadmill gait training with addition of 5% load proved to be a better experimental condition than the others because it provided greater gains in a number of variables (space-time and angular gait) and in the motion function, becoming a therapy capable of effectively improving the progress of individuals with PD

Efeitos do treino em esteira na marcha com dupla tarefa de indivíduos com doença de Parkinson: ensaio clínico controlado randomizado

Background: The gait automaticity loss difficults realization of concurrent activities - Dual Task (DT). In these situations, individuals with Parkinson`s disease (PD) show a significant reduction in gait velocity and stride length, as strides variability and asymmetry increased, factors predisposing to falls. However, recent studies have shown that training involving DT may cause subsequent improvements in gait variables with DT in individuals with PD. The treadmill use was adopted by this study, by promoting greater regularity in step and enhance training. Objective:To investigate immediate effects of gait training associated with cognitive tasks on gait in individuals with PD. Methods: Twenty-two volunteers were randomly divided into two groups: control group (n = 11), who performed gait training on a treadmill for 20 minutes, and the experimental group (n = 11), who performed treadmill gait training for 20 minutes associated with cognitive tasks of verbal fluency, memory, and spatial planning. Participants were evaluated in phase on of antiparkinsonian medication as the demographic, clinical and anthropometric (identification form), cognitive status (Montreal Cognitive Assessment - MoCA), executive function (Frontal Assessment Battery), level of physical disability (Hoehn and Yahr Modified), motor and functional status (Unified Rating Scale for Parkinson`s Disease - UPDRS), and kinematics (Qualisys Motion Capture System). Results: There were not differences between groups, but both showed improvement after the intervention. The control group had an increase in velocity (p = 0.008), stride length (p = 0.04), step length (p = 0.02) and decreased double support time(p = 0.03). The experimental group showed an increase in speed (p = 0.002), stride length (p = 0.008), step length (p = 0.02) and cadence (p = 0.01), as well as a decrease in the width stride (p = 0.001) and total support time (p = 0.02). As the angular variables, the experimental group had a significant increase in the initial contact angle of ankle (p = 0.01). Conclusion: The gait training combined with cognitive activities didn`t provide significant improvements in gait variables with DT, but this study was the first to demonstrate that gait training on treadmill as simple task minimized the negative interference of DT in PD

Efeitos das técnicas breath-stacking e espirometria de incentivo nos volumes da caixa torácica em pacientes com Doença de Parkinson

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Efeitos da prática mental na marcha de indivíduos com doença de parkinson: ensaio clínico randomizado

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

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 da estimulação da medula espinhal como modelo de tratamento da doença de parkinson no primata Callithrix jacchus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Déficits de memória induzidos por baixas doses de reserpina em ratos: possível relação com prejuízos no processamento emocional na Doença de Parkinson

We have recently verified that the monoamine depleting drug reserpine at doses that do not modify motor function - impairs memory in a rodent model of aversive discrimination. In this study, the effects of reserpine (0.1-0.5 mg/kg) on the performance of rats in object recognition, spatial working memory (spontaneous alternation) and emotional memory (contextual freezing conditioning) tasks were investigated. While object recognition and spontaneous alternation behavior were not affected by reserpine treatment, contextual fear conditioning was impaired. Together with previous studies, these results suggest that mild monoamine depletion would preferentially induce deficits in tasks involved with emotional contexts. Possible relationships with cognitive and emotional processing deficits in Parkinson disease are discussed

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

Modelo animal da Doença de Parkinson baseado na expressão de alfa - sinucleína: caracterização comportamental, eletrofisiológica e avaliação dos efei tos da estimulação da medula espinhal

Parkinson disease (PD) is associated with motor symptoms and dopaminergic cell loss in the nigrostriatal pathway. Alpha-synuclein is the major component of the Lewy bodies, the biological hallmarks of disease, and has been associated with familial cases of PD. Recently, the spinal cord stimulation (SCS) showed to be effective to alleviate the Parkinson symptoms in animal models and human patients. In this project, we characterized the motor and electrophysiological effects of alpha-synuclein overexpression in the substantia nigra of rats. We further investigated the effects of spinal electrical stimulation, AMPT and L-dopa administration in this model. Method: Sprague-Dawley rats were injected with empty viral vector or the vector carrying the gene for alpha-synuclein in the substantia nigra, and were tested weekly for 10 weeks in the open field and cylinder tests. A separated group of animals implanted with bilateral electrode arrays in the motor cortex and the striatum were recorded in the open field, during the SCS sessions and the pharmacological experiments. Results: Alpha-synuclein expression resulted in motor asymmetry, observed as the reduction in use of contralateral forepaw in the cylinder test. Animals showed an increase of local field potential activity in beta band three and four weeks after the virus injection, that was not evident after the 5th week. AMPT resulted in a sever parkinsonian state, with reduction in the locomotor activity and significant peak of oscillatory activity in cortex and striatum. SCS was effective to alleviate the motor asymmetry at long term, but did not reduce the corticostriatal low frequency oscillations observed 24 hs after the AMPT administration. These oscillations were attenuated by L-dopa that, even as SCS, was not effective to restore the locomotor activity during the severe dopaminergic depletion period. Discussion: The alpha-synuclein model reproduces the motor impairment and the progressive neurodegenerative process of PD. We demonstrated, by the first time, that this model also presents the increase in low frequency oscillatory activity in the corticostriatal circuit, compatible with parkinsonian condition; and that SCS has a therapeutic effect on motor symptom of this model.

Relação do polimorfismo BDNF val66met e níveis periféricos de BDNF com a doença de Parkinson e sua sintomatologia

Neurodegenerative diseases are frequently studied due to the increasing number of cases associated with the populational ageing and to the impact on the conditions on the quality of life. Parkinson’s disease (DP) is the second most frequent neurodegenerative disease. Despite the fact that its etiology is not completely understood, it is known that DP is caused by environmental and genetic factors. Thus, the investigation of etiologic factors and mechanisms responsible for the changes that lead to DP may help early diagnostic and prevention. A possible association between DP and the common polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies with contrasting results. For this reason, the aim of this study is to investigate if the BDNF Val66Met polymorphism is related to susceptibility to DP in a cohort of Brazilian patients. Additionaly, we verify if the presence of the polymorphism implies in alterations in the BDNF whole blood concentrations, as well as variations in symptomatology. The sample comprised Brazilian patients accompanied by the neurology service of the Onofre Lopes University Hospital (HUOL) and healthy controls (CTRL). The motor aspects of DP were evaluated by Hoehn e Yahr Scale (HY), Unified Parkinson’s Disease Rating Scale (UPDRS) and Schwab & England Scale (SE). For the evaluation of non-motor symptoms were used the following instruments: Frontal Assessment Battery (BAF), Mini-Mental State Examination (MEEM), Beck Depression Inventory (IDB) and the Beck Anxiety Inventory (IAB). Blood samples were collected for BDNF Val66Met polymorphism genotyping and BDNF whole blood measurement. As expected, DP patients performed worse in motor, cognitive and emotional battery of questionnaires. Alleles distribution between DP and CTRL was not significantly different, but the A/G genotype was significantly associated with a protector factor for DP. In contrast, the G/G genotype was significantly associated with depression and anxiety development in DP patients. However, BDNF concentrations were not different between genotypes or groups. This is the first study of genetic association of this polymorphism with DP in Brazilian subjects and the first one that associate A/G genotype with protection against DP.

Avaliação dos efeitos agudos de diferentes niveis de PEP sobre o padrão respiratório e volumes operacionais de pacientes com Parkinson

Objetivo: Determinar os efeitos agudos de diferentes intensidades de pressão expiratória positiva sobre o padrão respiratório e volumes operacionais de pacientes com doença de Parkinson. Métodos: Foram eleitos para o estudo 23 pacientes em estágios II ou III da doença, estando na condição ON , sendo 8 excluídos, e 15 controles saudáveis. Os indivíduos foram submetidos a uma avaliação inicial, constando de dados gerais, avaliação antropométrica, função pulmonar e força muscular respiratória. Após esta etapa inicial, realizou-se a avaliação dos volumes pulmonares com pletismografia optoeletrônica associado a utilização de pressão expiratória positiva (PEP) em três intensidades de pressão positiva, 10 cmH2O, 15 cmH2O e 20 cmH2O em ordem aleatória. Resultados: O grupo Parkinson apresentou valores espirométricos e de força muscular respiratória significativamente menores que o grupo controle (p<0.01). Houve diferença nos valores de volume corrente (Vt) do grupo Parkinson em relação ao grupo controle na respiração tranqüila (p<0.001) e aumento no Vt do grupo Parkinson com uso das três intensidades de PEP (p<0.001), sem diferenças estatisticamente significativas entre as intensidades e com diferença na distribuição compartimental do Vt entre os grupos (p<0.001). O fluxo inspiratório médio e o volume minuto do grupo Parkinson foram menores em relação ao grupo controle na respiração tranqüila (p<0.001) e aumentaram com o uso das três intensidades de PEP (p<0.001), sem diferenças estatisticamente significativas entre as intensidades. Houve diferença na variação dos volumes operacionais entre os grupos em todas as intensidades de PEP (p < 0.001). O volume pulmonar expiratório final não aumentou no grupo Parkinson com uso de PEP. O volume pulmonar inspiratório final aumentou no grupo Parkinson em todas intensidades de PEP (p < 0.001), não havendo diferenças entre as intensidades. Conclusão: Os pacientes com doença de Parkinson apresentam alterações em diferentes componentes do padrão respiratório e a terapia com PEP determina modificações clinicamente importantes nos volumes pulmonares, considerando a intensidade de 10 cmH2O suficientes para este objetivo terapêutico

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.

Interferindo com oscilações de alta frequência no hipocampo epiléptico: consequências para as crises espontâneas

Conselho Nacional de Desenvolvimento Científico e Tecnológico

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

Avaliação dos efeitos do extrato de Passiflora cincinnata Masters em camundongos: efeito na ansiedade e potencial neuroprotetor

Anxiety disorders and Parkinson’s disease (PD) affect a large portion of the world population. Indeed, therapeutic alternatives available do not contribute to improve most clinical conditions and/or are linked with undesirable side effects. Thus, there is a great demand for the development of new drugs to treatment of these diseases. Passiflora cincinnata Mast. is a native species present in several Brazilian states, popularly known as “maracujá do mato”, “maracujá tubarão” or “maracujá mochila”. Additionally, species of Passiflora genus are traditionally known for their exotic flowers, edible fruits with pronounced flavor and for their sedative, tranquilizer and anxiolytic properties reported by folk medicine. These plants possess important organic compounds such as phenols, cyanogenic glycosides, flavonoids and alkaloids, which are responsible for the anxiolytic, antioxidant, anti-inflammatory, antihyperglycemic, among others activities when tested in mammals. Despite this fact, only a few studies have been conducted to investigate the possible in vivo biological effects of Passiflora cincinnata Mast extracts. Thereby, in this study we evaluated the effects of the alcoholic extract of this plant in anxiety and PD animal model. Mice acutely or chronically administered with ethanolic extract of P. cincinnata do not showed any anxiogenic- or anxyolitic-like effect in elevated plus maze (EPM). In order to reproduce PD symptom’s in mice, we administered repeated injections of reserpine which progressively induced motor impairments such as increase in catalepsy, oral movements, and reduction of the average speed of the animals in the open field, as well as depleted dopamine prodution in SNpc cells. Furthermore, this treatment resulted in the loss of aversive memory recall in mice when undergoing PMDAT. Yet, passiflora group also show this amnesic profile. However, animals treated concomitantly with the alcoholic extract of Passiflora cincinnata Mast. showed higher latency for the onset of motor impairment evaluated by catalepsy. Thus, our results shows that the alcoholic extract of the plant P. cincinnata was able to delay the onset of the catalepsy induced by reserpine administration, plus reverted the depletion of dopamine production in SNpc cells.