Modulation of neuroinflammation by dietary flavonoids

There is increasing evidence to suggest neuroinflammatory processes contribute to the cascade of events that lead to the progressive neuronal damage observed in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. The molecular mechanisms underlying such neurodegenerative processes are rather complex and involve modulation of the mitogen-activated protein kinase (MAPK) and NF-κB pathways leading to the generation of nitric oxide (NO). Such a small molecule may diffuse to the neighbouring neurons and trigger neuronal death through the inhibition of mitochondrial respiration and increases in the reactive oxygen and nitrogen species. Recently, attention has focused on the neuroprotective effects of flavonoids which have been effective in protecting against both age-related cognitive and motor decline in vivo. Although, the precise mechanisms by which flavonoids may exert their neuroprotective effects remain unclear, accumulating evidence suggest that they may exert their neuroprotective effects through the modulation of the MAP Kinase and PI3 Kinase signaling pathways. The aim of the present chapter is to highlight the potential neuroprotective role of dietary flavonoids in terms of their ability to modulate neuroinflammation in the central nervous system. We will provide an outline of the role glial cells play in neuroinflammation and describe the involvement of inflammatory mediators, produced by glia, in the cascade of events leading to neuronal degeneration. We will then present the evidence that flavonoids may modulate neuroinflammation by inhibiting the production of these inflammatory agents and summarise their potential mechanisms of action.

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

Proposta de Intervenção para Auxiliar a Reabilitação Motora e Cognitiva de Pacientes com Acidente Vascular Cerebral

Stroke is the leading cause of combined motor and cognitive disability worldwide. The rehabilitation of stroke patients is mostly directed towards motor recovery through the training of the affected member under supervision of a Physical Therapist. In the present study we introduce a new approach for both cognitive and motor therapy, which relies on motor imagery of the upper limbs and working memory training. This therapy should be utilized as an adjuvant to physical therapy. Ten individuals (5 men and 5 women) were selected for the pilot study, all of them in the acute phase of the first ischemic stroke episode. The control group had 5 individuals who were submitted to physical therapy only, whilst the other 5 patients in the experimental group also performed the cognitive and motor training with a video game specially built for this study. Two patients left the experimental group before the end. Total training lasted for 9 weeks, 2 times a week, for half an hour. Patients reported they enjoyed playing the game, even though it required a lot of mental effort, according to them. Plus, they considered it had a beneficial influence in their activities of daily living. No side effects were reported. Preliminary results suggest there is a difference between groups in cognitive and upper limb motor evaluation following the intervention. It is important to notice that our conclusions are limited due the small sample number. Overall, this work is supported by other studies in literature focused in rehabilitation with motor imagery and working memory and indicate a continuity of the research, increasing total training hours

Apatia, funções cognitivas e funcionalidade motora em idosos com doença de Alzheimer

The aims of this study were to characterize the presence of apathy in patients with AD, determine the relationship between apathy, motor function and cognitive function, and to verify differences among patients stratified by level of apathy in relation to cognitive and motor abilities. Methods: A cross-sectional study was conducted of 37 patients with AD. The following tests were used: MoCA, the Frontal Assessment Battery, Verbal Fluency, Clock Drawing Test, Andreotti & Okuma Battery Tests, Sit and Reach, Resistance of Upper Limbs - AAHPERD Battery Test, Sit and Lift Chair and the Apathy domain of the Neuropsychiatric Inventory. After verifying the normality of the data distribution, comparisons were made using Student's t-test and the U Mann Whitney test; relationships were also assessed using Pearson's and Spearman's correlation coefficients. All analyses were considered to be statistically significant at a p-value of 0.05. Results: 46% of participants in this study showed mild symptoms of apathy. Significant and weak associations were found (p=0.04) between apathy and the attention domain on the MoCA and between apathy and the Walk Test. Analysis of differences in cognitive and motor functions according to participants' level of apathy revealed no significant differences for any of the variables. Conclusion: Apathy was reflected in attention and the Walk Test, suggesting these variables may be related to cognitive and functional decline in AD patients.

Sensorimotor Integration in Dyslexic Children under Different Sensory Stimulations

Dyslexic children, besides difficulties in mastering literacy, also show poor postural control that might be related to how sensory cues coming from different sensory channels are integrated into proper motor activity. Therefore, the aim of this study was to examine the relationship between sensory information and body sway, with visual and somatosensory information manipulated independent and concurrently, in dyslexic children. Thirty dyslexic and 30 non-dyslexic children were asked to stand as still as possible inside of a moving room either with eyes closed or open and either lightly touching a moveable surface or not for 60 seconds under five experimental conditions: (1) no vision and no touch; (2) moving room; (3) moving bar; (4) moving room and stationary touch; and (5) stationary room and moving bar. Body sway magnitude and the relationship between room/bar movement and body sway were examined. Results showed that dyslexic children swayed more than non-dyslexic children in all sensory condition. Moreover, in those trials with conflicting vision and touch manipulation, dyslexic children swayed less coherent with the stimulus manipulation compared to non-dyslexic children. Finally, dyslexic children showed higher body sway variability and applied higher force while touching the bar compared to non-dyslexic children. Based upon these results, we can suggest that dyslexic children are able to use visual and somatosensory information to control their posture and use the same underlying neural control processes as non-dyslexic children. However, dyslexic children show poorer performance and more variability while relating visual and somatosensory information and motor action even during a task that does not require an active cognitive and motor involvement. Further, in sensory conflict conditions, dyslexic children showed less coherent and more variable body sway. These results suggest that dyslexic children have difficulties in multisensory integration because they may suffer from integrating sensory cues coming from multiple sources. © 2013 Viana et al.

Efeito do treinamento com pesos na apatia, funções cognitivas frontais e funcionalidade motora em pacientes com doença de Alzheimer

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Relação entre nível de atividade física, cognição, processamento da informação e funcionalidade motora de idosos no estágio leve da doença de Alzheimer

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A interferência da tarefa dupla, motora e cognitiva, no andar de pacientes com doença de Parkinson

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estudo sobre o efeito do incremento de tarefas cognitivas sobre o padrão de marcha de adultas jovens

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito combinado do exercício físico e da degradação da matriz extracelular na plasticidade do córtex cerebral após isquemia

O acidente vascular cerebral (AVC) é a maior causa de mortes e incapacidades neurológicas no Brasil, e mais de 80% deles são decorrentes de evento isquêmico. Os sobreviventes de AVC apresentam uma variedade de déficits motores, cognitivos e sensoriais, que prejudicam suas atividades de vida diária, limitando assim sua independência. Portanto, torna-se cada vez mais necessário elaborar estratégias terapêuticas que promovam a recuperação funcional de pacientes acometidos por AVC. Após isquemia do tecido nervoso, ocorre no meio extracelular a super expressão de moléculas inibitórias a regeneração neuronal e à plasticidade sináptica, como os proteoglicanos de sulfato de condroitina (PGSCs), o principal componente das redes perineuronais (RPNs). A remoção destas moléculas com a ação da enzima condroitinase ABC (ChABC) tem sido usada como estratégia para induzir a plasticidade neuronal. Outro fator que tem sido utilizado para estimular a neuroplasticidade é o exercício físico específico para o membro afetado após AVC. O exercício físico está relacionado à liberação de neurotrofinas, importantes para a regeneração do sistema nervoso. Portanto, a remoção dos PGSCs junto com o exercício físico pode potencializar a indução da plasticidade cerebral e recuperação funcional após lesão isquêmica experimental na área sensório-motora de ratos. Para testar nossa hipótese, utilizamos n=16 ratos (Ratus norvergicus) da linhagem Wistar, divididos nos seguintes grupos experimentais (todos com sobrevida de 21 dias após AVC isquêmico): Grupo Controle ou BSA (Isquemia experimental, implante de Elvax saturado com BSA); Grupo Exercício (Isquemia experimental, implante de Elvax saturado com BSA + exercício físico específico); Grupo ChABC (Isquemia experimental, implante de Elvax saturado com ChABC); e Grupo ChABC + Exercício (Isquemia experimental, implante de Elvax saturado com ChABC + exercício físico específico). A lesão isquêmica foi induzida através de microinjeções do vasoconstritor Endotelina-1 (ET-1) no córtex sensório-motor, na representação da pata anterior. Logo em seguida foi implantado uma microfatia de polímero de Etileno vinil acetato saturado com ChABC (grupos ChABC e ChABC + Exercício) ou BSA (grupos Controle e Exercício). Foram avaliadas a área de lesão e a degradação dos PGSCs, além da recuperação funcional da pata afetada através do teste da exploração vertical e do teste da escada horizontal. Avaliamos a área de lesão (mm²) com auxílio do programa ImageJ (NIH, USA), delimitando a área com palor celular e também marcada com azul de colanil que estava presente na solução de injeção do peptídeo vasoconstritor ET-1 e verificamos que não houve diferença significativa no tamanho da área de lesão entre os grupos Controle (0,48±0,12), Exercício (0,46±0,05), ChABC (0,50±0,18) e ChABC + Exercício (0,55±0,05) (ANOVA, pós-teste de Tukey, ***p<0,001; **<0,01; *p<0,5). Animais que foram submetidos à remoção enzimática dos PGSCs apresentaram imunomarcação para o anticorpo anti-condroitin-4-sulfato (C4S) na área de lesão ao final da sobrevida, não havendo evidencias de degradação de PGSCs nos grupos Controle e Exercício. Verificamos ainda no teste do cilindro que a indução da lesão isquêmica não provocou perda funcional ampla, não alterando o comportamento exploratório, nem a frequência de uso da pata anterior afetada dos animais após a lesão (grupo Controle: pré-lesão ou baseline (0,33±0,10), 3 (0,29±0,17), 7 (0,30±0,10), 14 (0,29±0,16) e 21 (0,27±0,13) dias após a lesão; grupo Exercício: pré-lesão ou baseline (0,30±0,12), 3 (0,32±0,24), 7 (0,19±0,37), 14 (0,31±0,10) e 21 (0,32±0,09) dias após a lesão; grupo ChABC: pré-lesão ou baseline (0,34±0,07), 3 (0,20±0,11), 7 (0,23±0,07), 14 (0,33±0,14) e 21 (0,39±0,16) dias após a lesão; grupo ChABC + Exercício: pré-lesão ou baseline (0,34±0,04), 3 (0,20±0,09), 7 (0,26±0,04), 14 (0,18±0,08) e 21 (0,27±0,04) dias após a lesão) (ANOVA, pós-teste de Tukey, ***p<0,001; **<0,01; *p<0,5). O grupo que teve apenas a remoção dos PGSCs apresentou um melhor desempenho motor no teste da escada horizontal, mantendo sua frequência de acertos quando comparado aos demais grupos, sendo que ao final da sobrevida de 21 dias, os grupos Controle e ChABC + Exercício alcançaram uma recuperação espontânea (equivalente ao teste pré-lesão), se aproximando do grupo ChABC. Apenas o grupo tratado somente com Exercício não alcançou a recuperação espontânea, apresentando um desempenho motor significativamente inferior aos demais grupos em todos os momentos de reavaliação (grupo Controle: pré-lesão ou baseline (7,70±0,54), 3 (5,30±0,71), 7 (5,4±1,14), 14 (5,20±0,37) e 21 (6,70±0,48) dias após a lesão; grupo Exercício: pré-lesão ou baseline (8,40±0,28), 3 (4,30±0,48), 7 (4,75±0,50), 14 (5,35±0,41) e 21 (5,05±0,67) dias após a lesão; grupo ChABC: pré-lesão ou baseline (7,65±0,97), 3 (6,90±0,65), 7 (7,80±0,37), 14 (7,15±0,87) e 21 (7,45±0,32) dias após a lesão; e grupo ChABC + Exercício: pré-lesão ou baseline (8,10±0,22), 3 (3,65±1,48), 7 (4,95±1,06), 14 (7,35±0,37) e 21 (6,70±0,48) dias após a lesão (ANOVA, pós-teste de Tukey, ***p<0,001; **<0,01; *p<0,5). Portanto, a remoção dos PGSCs, o exercício físico forçado precoce e sua associação não influenciaram no tamanho da área de lesão após isquemia focal no córtex sensório-motor. Porém, apenas a remoção dos PGSCs das redes perineuronais melhorou precocemente o desempenho motor do membro afetado após isquemia focal no córtex sensório-motor. Enquanto que a remoção dos PGSCs associada ao exercício físico melhorou o desempenho motor do membro afetado após a lesão, porém essa melhora foi tardia. E o exercício físico aplicado precocemente após isquemia focal no córtex sensório-motor prejudicou o desempenho motor do membro afetado.

Efeitos do exercício físico multimodal nas concentrações plasmáticas de biomarcadores, funções cognitivas e funcionalidade em pacientes com doença de Alzheimer

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

Correlações entre sono-vigília, memória e melatonina em Síndrome de Williams-Beuren

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Potencial Cognitivo Auditivo e vectoeletronistagmografia em escolares com dislexia e distúrbios de aprendizagem

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos do extrato de soja (Glycine max) na motricidade, nas funções cognitivas e sintomas do climatério: um estudo duplo cego

Pós-graduação em Ciências da Motricidade - IBRC

Desenvolvimento de bebês nos dois primeiros meses de vida: variáveis maternas e sociodemográficas

In the present study, participated sixteen mothers. We discuss about risk factors for the development of the baby, especially main measurements maternal and sociodemographic. Mothers were interviewed and inventories to assess anxiety and stress. The babies were assessed from 'Inventário Operacionalizado Portage. The results pointed positive correlations between anxiety and self-care, and negative associations between maternal stress and cognitive development of infants. There were significant correlations between maternal age and cognitive, and motor development in the second month (p=0.005; 013). Gestational age was significant for the motor area in the second month of a baby's life (p=0.026), however this correlate was negative. The variable birth weight showed significant difference in cognition and negative in the second month (p=0.29); and maternal education was significant positive for the language area in the first month (p=0.000). These results emphasized the importance of guidance and monitoring of mothers during the postpartum.