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

Identification of sexually dimorphic gene expression in brain tissue of the fish Leporinus macrocephalus through mRNA differential display and real time PCR analyses

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

Locomoção, distúrbios neuropsiquiátricos e alterações do sono de pacientes com demência e seus cuidadores

INTRODUÇÃO: Os distúrbios neurodegenerativos representam condições clínicas graves, por provocar declínio neuropsíquico. OBJETIVO: Analisar a prevalência dos distúrbios neuropsiquiátricos em pacientes com demência, em relação à sua locomoção (independentes vs. dependentes), e no que se refere ao desgaste emocional e à qualidade do sono dos cuidadores. MATERIAIS E MÉTODOS: Participaram do estudo 34 sujeitos, assim divididos: dez pacientes independentes para locomoção e sete dependentes (cadeirantes); dez cuidadores dos pacientes independentes e sete cuidadores de pacientes dependentes. Os sujeitos foram avaliados no Ambulatório de Neuropsiquiatria da Universidade Estadual de Campinas. Para avaliar as funções cognitivas, utilizou-se o CAMCOOG; para quantificar frequência, intensidade e desgaste do cuidador, aplicou-se o Inventário Neuropsiquiátrico; e para mensurar as alterações do sono dos cuidadores, foi utilizado o Miniquestionário do Sono. A análise estatística foi realizada por meio dos testes U - Mann Whitney e índice de correlação de Spearman, ambos com 5% de significância. RESULTADOS: Com relação à prevalência dos distúrbios neuropsiquiátricos entre os pacientes, observou-se diferença estatisticamente significativa entre os grupos, especificamente no que se refere à irritabilidade (p < 0,05) e ao escore total dos distúrbios neuropsiquiátricos (p < 0,01). Também foram encontradas diferenças entre os grupos de cuidadores, com relação às alterações do sono (p < 0,05). CONCLUSÃO: Idosos independentes para locomoção apresentam menor prevalência dos distúrbios neuropsiquiátricos, quando comparados a idosos dependentes de cadeira de rodas. A locomoção parece não influenciar no desgaste físico e emocional do cuidador, mas constitui uma variável relevante na qualidade do sono dos cuidadores de idosos com diagnóstico de demência vascular e mista.

Physical activity attenuates neuropsychiatric disturbances and caregiver burden in patients with dementia

INTRODUCTION: A significant benefit from physical activity has recently been described in some patients who suffer from neurodegenerative diseases. OBJECTIVE: To assess the effects of physical activity on neuropsychiatric disturbances in demented patients and on the mental burden of their caregivers. METHODS: Assisted by a public geriatric psychiatry clinical unit, we studied 59 patients with dementia. Patients were divided into three groups according to their diagnosis and level of physical activity. Data were assessed through a semi-structured interview. Patients were evaluated with the Neuropsychiatric Inventory, the Mini-Sleep Questionnaire and the Baecke Questionnaire. The data were statistically analyzed using the Mann-Whitney U test and linear regression, with the level of significance set at 5%. RESULTS: Patients with Alzheimer's or vascular dementia who engaged in physical activity had fewer neuropsychiatric symptoms than those who did not. When compared to the control group, the caregivers of patients with vascular dementia who engaged in physical activity had a reduced burden. CONCLUSION: The regular practice of physical activity seems to contribute to a reduction in neuropsychiatric symptoms in dementia patients and to attenuate the burden of the caregivers of those patients.

Neuroglobin and cytoglobin: two new members of globin family

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Molecular physicochemical parameters predicting antioxidant activity of Brazilian natural products

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

Aspectos físicos e mentais na qualidade de vida de pacientes com doença de Parkinson idiopática

A doença de Parkinson (DP) é um distúrbio crônico e progressivo, caracterizado pela degeneração de neurônios dopaminérgicos da substantia nigra mesencefálica. A lesão das vias subcorticais, em especial a nigro-estriato-palidal, é particularmente comum e ocasiona uma série de sinais e sintomas incapacitantes. O objetivo deste trabalho foi analisar a qualidade de vida (QV) relacionada à saúde de sujeitos com DP e compará-la à de indivíduos controles saudáveis. Foram avaliados 40 sujeitos com idades entre 61 e 83 anos, de ambos os sexos, que foram divididos em dois grupos: grupo Parkinson (n=21), composto por sujeitos com DP idiopática, e grupo controle (n=19), de indivíduos sem distúrbios neurodegenerativos. Para a coleta de dados, foi utilizada a versão brasileira do questionário Brasil SF-36. Os resultados foram analisados estatisticamente, com nível de significância fixado em 1%. Os sujeitos do grupo Parkinson apresentaram escores significativamente mais baixos do que os do grupo controle, tanto no domínio físico quanto no mental, medidos pelo SF-36. Essa baixa QV provavelmente é explicada pela co-ocorrência de fenômenos neurodegenerativos e do sofrimento psíquico gerado pela doença e pelo estigma que ela produz. Abordagens interdisciplinares devem ser estimuladas a pacientes com DP, com o objetivo de melhorar sua qualidade de vida e postergar o declínio físico e mental inerente às condições degenerativas.

New anti-Alzheimer drugs from biodiversity: the role of the natural acetylcholinesterase inhibitors

Alzheimer's disease (AD) is a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays, drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only four commercial medicines approved for treatment of AD, and natural products have played an important alternative role in the research for new acetylcholinesterase inhibitors, as exemplified through the discovery of galantamine. This profile conducts us to give in this paper an overview relating the several classes of natural products with anti-cholinesterasic activity as potential templates to the design of new selective and powerful anti-Alzheimer drugs.

Produtos naturais como candidatos a fármacos úteis no tratamento do mal de Alzheimer

Alzheimer's disease (AD) is a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only four commercial medicines approved for treatment of AD and natural products have played an important role in the research for new acetylcholinesterase inhibitors.

El tratamiento fisioterapéutico ¿es efectivo en el mantenimiento físico y en la reducción del declive cognitivo de las demencias?

Introduction. Dementia is a chronic and neurodegenerative disease responsible for a progressive decline of cognition and physical capacity. Objective: To verify the effectiviness of three months of physiotherapy intervention on cognitive functions and balance of institutionilized elderly people with dementia. Patients and methods. This study has comprised thirty subjects, divided in two groups: EG (experimental group) and CG (control group). EG was composed by 15 participants with mean age of 71,6 ± 8,5 years and scholarity of 4,7 ± 4,2 years. CG was formed by 15 subjects with mean age of 78,5 ± 7,6 years and scholarity of 2,2 ± 1,8 years. The sample was evaluated by means of the following instruments: Mini-Mental State Examination, Semantic Verbal Fluency test, Clock Drawing test, Berg Balance Scale and Timed Get Up and Go test. The statistical procedures were done by means of Multivariate Analisis of Variance (MANOVA), with significance of 5 % (p < 0,05). Results. The results has shown a heterogeneity of both groups related to age (F = 0,2, p < 0,05) and scholarity (F = 2,6, p < 0,05). MANOVA pointed beneficts of physiotherapy on balance (F = 7,3, p < 0,01) but not on cognitive functions (F = 0,3, p > 0,05). Conclusions. Three months of physiotherapy were effective to improuve physical capacity of institucionilized elderly people with dementia. Neverthless, it was not able to minimize cognitive decline commonly seen on dementia. The question if a prolonged intervention could propitiate cognitive beneficts remains, specially in a more homogeneous groups.

Influencia de la actividad física en la enfermedad de Alzheimer: un caso clínico

Alzheimer's dementia (AD) is a neurodegenerative disorder that causes motor and cognitive decline. The aim of this study was to analyze the influence of a specific physical activity program on the cognitive, depressive symptoms and functional capacity of patients with diagnosis of probable AD. The subject, a 79-year old woman, participated in this program for three months, with 50 min sessions three times a week. The instruments used were the Cambridge Cognitive Examination; the Geriatric Depression Scale; and the Battery of the American Alliance for Health Physical Education, Recreation and Dance. The results in relationship with the depressive symptoms and functional capacity were significantly positive. There were no changes in regards to the patient's cognitive functions. In conclusion, this physical activity program seems to be an important part of the treatment for patients with AD, as it improves the functional capacity and also stimulates cognitive tasks. © 2008 Asociación Española de Fisioterapeutas.

Improving Parkinson's disease identification through evolutionary-based feature selection

Parkinson's disease (PD) automatic identification has been actively pursued over several works in the literature. In this paper, we deal with this problem by applying evolutionary-based techniques in order to find the subset of features that maximize the accuracy of the Optimum-Path Forest (OPF) classifier. The reason for the choice of this classifier relies on its fast training phase, given that each possible solution to be optimized is guided by the OPF accuracy. We also show results that improved other ones recently obtained in the context of PD automatic identification. © 2011 IEEE.

Apocynin: Chemical and biophysical properties of a NADPH oxidase inhibitor

Apocynin is the most employed inhibitor of NADPH oxidase (NOX), a multienzymatic complex capable of catalyzing the one-electron reduction of molecular oxygen to the superoxide anion. Despite controversies about its selectivity, apocynin has been used as one of the most promising drugs in experimental models of inflammatory and neurodegenerative diseases. Here, we aimed to study the chemical and biophysical properties of apocynin. The oxidation potential was determined by cyclic voltammetry (Epa = 0.76V), the hydrophobicity index was calculated (logP = 0.83) and the molar absorption coefficient was determined (ε275nm = 1.1 × 104 M-1 cm-1). Apocynin was a weak free radical scavenger (as measured using the DPPH, peroxyl radical and nitric oxide assays) when compared to protocatechuic acid, used here as a reference antioxidant. On the other hand, apocynin was more effective than protocatechuic acid as scavenger of the non-radical species hypochlorous acid. Apocynin reacted promptly with the non-radical reactive species H2O2 only in the presence of peroxidase. This finding is relevant, since it represents a new pathway for depleting H2O2 in cellular experimental models, besides the direct inhibition of NADPH oxidase. This could be relevant for its application as an inhibitor of NOX4, since this isoform produces H 2O2 and not superoxide anion. The binding parameters calculated by fluorescence quenching showed that apocynin binds to human serum albumin (HSA) with a binding affinity of 2.19 × 104 M -1. The association did not alter the secondary and tertiary structure of HSA, as verified by synchronous fluorescence and circular dichroism. The displacement of fluorescent probes suggested that apocynin binds to site I and site II of HSA. Considering the current biomedical applications of this phytochemical, the dissemination of these chemical and biophysical properties can be very helpful for scientists and physicians interested in the use of apocynin.

Validation of the brazilian version of the apathy inventory

Background Apathy is a frequent neuropsychiatric condition in neurodegenerative disorders, depression, and often in mild cognitive impairment. The Apathy Inventory (AI) is a reliable instrument for improving the accuracy of the apathy diagnosis. The aim was to establish the validity of the Apathy Inventory for the Brazilian community. Methods We established the concurrent validity, internal consistency, inter-rater reliability, and the sensitivity and specificity of AI for the Brazilian community in a cohort of 175 individuals with Alzheimer's disease, Parkinson's disease, depression, mild cognitive impairment, and healthy controls. The three dimensions of the AI (emotional blunting, lack of initiative, and lack of interest) were compared with the Apathy domain of the Neuropsychiatric Inventory-Clinician rating scale (NPI-C) in an independent scheme. Results The analyses demonstrated high correlation coefficients in AI's individual dimensions and in AI-total score (F = 0.965). Concerning the NPI-C/Apathy domain, intra-class correlation coefficients were also high (F = 0.977). Concurrent validity was high according to both raters on AI dimensions × NPI-C/Apathy domain and regarding total score (rater 1: rho = 0.956 vs. rater 2: rho = 0.970). The internal consistency of the AI was also high concerning the AI's individual dimensions and total score (rater 1: 0.945 vs. rater 2: 0.958). Conclusion We observed high internal consistency, high concurrent validity, and inter-rater reliability of the Apathy Inventory. In addition, we found that its sensitivity and specificity were high. We suggest that the Brazilian version of the Apathy Inventory would be an appropriate instrument to identify the apathy syndrome in Brazilian patients. © 2012 John Wiley & Sons, Ltd.

Treinamento aeróbio na aptidão funcional, cognitiva e biomarcadores da doença de Alzheimer em idosos sem demência: um estudo controlado

Pós-graduação em Ciências da Motricidade - IBRC