RESUMO
BACKGROUND: People with epilepsy (PWE) may have a sedentary lifestyle and less physical activity (PA) as they are often advised against engaging in sports, despite a plethora of evidence suggesting seizure control, major health and psychosocial benefits associated with PA. We aimed to investigate PWE's beliefs on PA and their level of PA compared to controls. METHODS: The Baecke questionnaire for measuring habitual PA in adults, comprising three domains (occupational PA, leisure, and locomotion), was applied in 97 consecutive PWE (96.9% with focal epilepsy, 39.2% well controlled with pharmacological treatment) and 45 healthy controls matched for gender, age, and socioeconomic characteristics. RESULTS: The total Baecke score was significantly lower in PWE than controls (7.6⯱â¯1.5 versus 8.2⯱â¯1.2; pâ¯<â¯0.01). PWE showed a significantly lower employment rate than controls (34.0% versus 73.3%; pâ¯<â¯0.01), and consequently lower occupational PA (pâ¯<â¯0.01). Physical exercise during sports time (pâ¯=â¯0.23) and leisure activities (pâ¯=â¯0.55) scores were similar between patients and controls. When PWE and controls' sociodemographic characteristics were analyzed together by multiple linear regression, 21% of the Baecke total score variation was explained by diagnosis of epilepsy (Bâ¯=â¯-0.26; pâ¯=â¯0.05), years of education (Bâ¯=â¯-0.35; pâ¯=â¯0.03), and occupational status (Bâ¯=â¯-0.41; pâ¯<â¯0.01). However, diagnosis of epilepsy alone explained only 4% (Bâ¯=â¯-0.64; pâ¯=â¯0.01) of Baecke total score variation. CONCLUSION: The level of PA in PWE is only slightly lower than in controls (8% lower score) and it may be explained by lower occupational PA, probably related to lower employment rate among PWE.
Assuntos
Epilepsia , Adulto , Estudos de Casos e Controles , Emprego , Epilepsia/epidemiologia , Exercício Físico , Humanos , Convulsões , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Sleepiness and cognitive impairment are common symptoms observed in patients with epilepsy. We investigate whether self-reported sleepiness is associated with cognitive performance in patients with refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Seventy-one consecutive patients with MTLE-HS were evaluated with the Stanford Sleepiness Scale (SSS) before neuropsychological evaluation. Their mean SSS scores were compared with controls. Each cognitive test was compared between patients with (SSS ≥ 3) or without sleepiness (SSS < 3). Imbalances were controlled by regression analysis. Patients reported a significantly higher degree of sleepiness than controls (p < 0.0001). After multiple linear regression analysis, only one test (RAVLT total) remained associated with self-reported sleepiness. CONCLUSION: Self-reported sleepiness was significantly higher in MTLE-HS patients than controls, but did not affect their cognitive performance. If confirmed in other populations, our results may have implications for decision making about sleepiness screening in neuropsychological settings.
Assuntos
Cognição/fisiologia , Epilepsia do Lobo Temporal/psicologia , Testes Neuropsicológicos , Autorrelato , Sonolência , Adulto , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Demografia , Epilepsia Resistente a Medicamentos/fisiopatologia , Escolaridade , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose/complicaçõesRESUMO
ABSTRACT Sleepiness and cognitive impairment are common symptoms observed in patients with epilepsy. We investigate whether self-reported sleepiness is associated with cognitive performance in patients with refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Seventy-one consecutive patients with MTLE-HS were evaluated with the Stanford Sleepiness Scale (SSS) before neuropsychological evaluation. Their mean SSS scores were compared with controls. Each cognitive test was compared between patients with (SSS ≥ 3) or without sleepiness (SSS < 3). Imbalances were controlled by regression analysis. Patients reported a significantly higher degree of sleepiness than controls (p < 0.0001). After multiple linear regression analysis, only one test (RAVLT total) remained associated with self-reported sleepiness. Conclusion: Self-reported sleepiness was significantly higher in MTLE-HS patients than controls, but did not affect their cognitive performance. If confirmed in other populations, our results may have implications for decision making about sleepiness screening in neuropsychological settings.
RESUMO A sonolência e o comprometimento cognitivo são queixas comuns na epilepsia. Investigamos se a sonolência relatada pelo paciente está associada ao desempenho cognitivo na epilepsia do lobo temporal mesial refratária com esclerose do hipocampo (ELTM-EH). 71 pacientes com ELTM-EH foram avaliados pela Escala de Sonolência de Stanford (ESS) antes da avaliação neuropsicológica. A média na ESS foi comparada com a de controles. Cada teste foi comparado entre os pacientes com sonolência (ESS ≥ 3) ou sem sonolência (ESS <3). Diferenças foram controladas por regressão logística múltipla. Os pacientes relataram uma sonolência maior do que os controles (p <0,0001). Após a regressão, a sonolência relatada pelos pacientes mostrou-se associada a apenas um teste (RAVLT total). Os pacientes com ELTM-EH referem mais sonolência do que os controles, mas esta não foi associada com a cognição. Se confirmado em outras populações, nossos resultados implicarão na tomada de decisão sobre o impacto da sonolência no contexto neuropsicológico.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Cognição/fisiologia , Epilepsia do Lobo Temporal/psicologia , Autorrelato , Sonolência , Testes Neuropsicológicos , Esclerose/complicações , Estudos de Casos e Controles , Demografia , Escolaridade , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia Resistente a Medicamentos/fisiopatologia , Hipocampo/patologia , Anticonvulsivantes/uso terapêuticoRESUMO
Interictal hypometabolism is commonly measured by 18-fluoro-deoxyglucose Positron Emission Tomography (FDG-PET) in the temporal lobe of patients with mesial temporal lobe epilepsy (MTLE-HS). Left temporal lobe interictal FDG-PET hypometabolism has been associated with verbal memory impairment, while right temporal lobe FDG-PET hypometabolism is associated with nonverbal memory impairment. The biochemical mechanisms involved in these findings remain unknown. In comparison to healthy controls (n=21), surgically treated patients with MTLE-HS (n=32, left side=17) had significant lower scores in the Rey Auditory Verbal Learning Test (RAVLT retention and delayed), Logical Memory II (LMII), Boston Naming test (BNT), Letter Fluency and Category Fluency. We investigated whether enzymatic activities of the mitochondrial enzymes Complex I (C I), Complex II (C II), Complex IV (C IV) and Succinate Dehydrogenase (SDH) from the resected samples of the middle temporal neocortex (mTCx), amygdala (AMY) and hippocampus (HIP) were associated with performance in the RAVLT, LMII, BNT and fluency tests of our patients. After controlling for the side of hippocampus sclerosis, years of education, disease duration, antiepileptic treatment and seizure outcome after surgery, no independent associations were observed between the cognitive test scores and the analyzed mitochondrial enzymatic activities (p>0.37). Results indicate that memory and language impairment observed in MTLE-HS patients are not strongly associated with the levels of mitochondrial CI, CII, SDH and C IV enzymatic activities in the temporal lobe structures ipsilateral to the HS lesion.
Assuntos
Encéfalo/metabolismo , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/patologia , Transtornos da Memória/etiologia , Complexos Multienzimáticos/metabolismo , Adulto , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/tratamento farmacológico , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Transtornos da Memória/diagnóstico por imagem , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Estatísticas não ParamétricasRESUMO
PURPOSE: The purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests. METHODS: Forty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline. KEY FINDINGS: Six (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of ≥8 points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function. SIGNIFICANCE: Impairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug-resistant MTLE.
Assuntos
Cognição/fisiologia , Disfunção Cognitiva/etiologia , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Complicações Pós-Operatórias , Adulto , Atenção/fisiologia , Brasil , Epilepsia Resistente a Medicamentos/cirurgia , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Destreza Motora/fisiologia , Testes Neuropsicológicos , Qualidade de Vida , Percepção Espacial/fisiologia , Lobo Temporal/fisiopatologia , Percepção Visual/fisiologiaAssuntos
Epilepsia Resistente a Medicamentos/enzimologia , Epilepsia do Lobo Temporal/enzimologia , Sistema Límbico/enzimologia , Transtornos Mentais/enzimologia , Mitocôndrias/enzimologia , Complexos Multienzimáticos/metabolismo , Adulto , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/psicologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/psicologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Sistema Límbico/patologia , Sistema Límbico/cirurgia , Masculino , Transtornos Mentais/complicações , Neocórtex/enzimologia , Neocórtex/cirurgia , Dados Preliminares , Estudos Prospectivos , Esclerose/enzimologia , Esclerose/patologia , Esclerose/psicologia , Esclerose/cirurgia , Lobo Temporal/enzimologia , Lobo Temporal/cirurgiaRESUMO
Moderate traumatic brain injury (TBI) might increase the vulnerability to neuronal neurodegeneration, but the basis of such selective neuronal susceptibility has remained elusive. In keeping with the disruption of the blood-brain barrier (BBB) caused by TBI, changes in BBB permeability following brain injury could facilitate the access of xenobiotics into the brain. To test this hypothesis, here we evaluated whether TBI would increase the susceptibility of nigrostriatal dopaminergic fibers to the systemic administration of 6-hydroxydopamine (6-OHDA), a classic neurotoxin used to trigger a PD-like phenotype in mice, but that in normal conditions is unable to cross the BBB. Adult Swiss mice were submitted to a moderate TBI using a free weight-drop device and, 5h later, they were injected intraperitoneally with a single dose of 6-OHDA (100mg/kg). Afterwards, during a period of 4weeks, the mice were submitted to a battery of behavioral tests, including the neurological severity score (NSS), the open field and the rotarod. Animals from the TBI plus 6-OHDA group displayed significant motor and neurological impairments that were improved by acute l-DOPA administration (25mg/kg, i.p.). Moreover, the observation of the motor deficits correlates with (i) a significant decrease in the tyrosine hydroxylase levels mainly in the rostral striatum and (ii) a significant increase in the levels of striatal glial fibrillary acidic protein (GFAP) levels. On the whole, the present findings demonstrate that a previous moderate TBI event increases the susceptibility to motor, neurological and neurochemical alterations induced by systemic administration of the dopaminergic neurotoxin 6-OHDA in mice.
Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Oxidopamina/toxicidade , Animais , Comportamento Animal , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Levodopa/metabolismo , Camundongos , Doenças Neurodegenerativas , Síndromes Neurotóxicas/metabolismo , Oxidopamina/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
OBJECTIVES: To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients. METHODS: Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS. RESULTS: The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2-14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity. SIGNIFICANCE: These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.
Assuntos
Lobectomia Temporal Anterior/psicologia , Epilepsia Resistente a Medicamentos/psicologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/psicologia , Epilepsia do Lobo Temporal/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida/psicologia , Adulto , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia do Lobo Temporal/diagnóstico , Feminino , Seguimentos , Hipocampo/patologia , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos , Psicometria , Esclerose , Adulto JovemRESUMO
Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20µg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10µg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10µg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity.
Assuntos
Potenciação de Longa Duração/fisiologia , Transtornos da Memória/fisiopatologia , Memória de Curto Prazo/fisiologia , Transtornos Parkinsonianos/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Discriminação Psicológica/fisiologia , Método Duplo-Cego , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/patologia , Atividade Motora , Oxidopamina , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/psicologia , Córtex Pré-Frontal/patologia , Ratos Wistar , Teste de Desempenho do Rota-Rod , Memória Espacial/fisiologia , Transmissão Sináptica/fisiologia , Técnicas de Cultura de TecidosRESUMO
Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the slow and progressive death of dopaminergic neurons in the (substantia nigra pars compact). Hypericum perforatum (H. perforatum) is a plant widely used as an antidepressant, that also presents antioxidant and anti-inflammatory properties. We evaluated the effects of H. perforatum on the turning behavior of rats submitted to a unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle as an animal model of PD. The animals were treated with H. perforatum (100, 200, or 400 mg/kg, v.o.) for 35 consecutive days (from the 28th day before surgery to the 7th day after). The turning behavior was evaluated at 7, 14 and 21 days after the surgery, and the turnings were counted as contralateral or ipsilateral to the lesion side. All tested doses significantly reduced the number of contralateral turns in all days of evaluation, suggesting a neuroprotective effect. However, they were not able to prevent the 6-OHDA-induced decrease of tyrosine hydroxylase expression in the lesioned striatum. We propose that H. perforatum may counteract the overexpression of dopamine receptors on the lesioned striatum as a possible mechanism for this effect. The present findings provide new evidence that H. perforatum may represent a promising therapeutic tool for PD.
A Doença de Parkinson é uma doença neurodegenerativa relacionada à idade, caracterizada pela morte lenta e progressiva de neurônios dopaminérgicos da substância negra pars compacta. O Hypericum perforatum (H. perforatum) é um fitoterápico utilizado como antidepressivo, apresentando propriedades antioxidantes, anti-inflamatórias e nootrópicas. Neste trabalho, avaliaram-se os efeitos do tratamento com H. perforatum no comportamento rotatório de ratos no modelo da doença de Parkinson induzido pela administração unilateral de 6-OHDA no feixe prosencefálico medial. Ratos Wistar machos foram tratados com H. perforatum (100, 200 ou 400 mg/kg, v.o.) por 35 dias (do 28º dia antes até o 7º dia após a lesão). As rotações ipsilaterais e contralaterais à lesão foram registradas no 7º, 14º e 21º dias após a cirurgia. As três doses de H. perforatum utilizadas reduziram o número de rotações contralaterais, indicando um possível efeito neuroprotetor da planta. Porém, o H. perforatum não impediu a redução na expressão da enzima tirosina hidroxilase no estriado lesionado, quantificada por Western blot. Propomos que o H. perforatum possa bloquear o aumento da expressão dos receptores dopaminérgicos no estriado lesionado com 6-OHDA. Entretanto, estudos adicionais são necessários para identificar o mecanismo exato pelo qual o H. perforatum reduziu o número de rotações contralaterais. Os resultados do presente estudo sugerem o H. perforatum como um potencial agente terapêutico para a doença de Parkinson.
Assuntos
Doença de Parkinson/diagnóstico , Hypericum , Oxidopamina/análise , Fármacos Neuroprotetores , FitoterapiaRESUMO
The epileptogenesis process involves cell signaling events associated with neuroplasticity. The mitogen-activated protein kinases (MAPKs) integrate signals originating from a variety of extracellular stimuli and may regulate cell differentiation, survival, cell death and synaptic plasticity. Here we compared the total and phosphorylated MAPKs (ERK1/2, JNK1/2 and p38(MAPK)) levels in the neocortex and hippocampus of adult Swiss male mice quantified by western blotting analysis 48 h after the last injection of pentylenetetrazole (PTZ), according to the kindling protocol (35 mg/kg, i.p., on alternated days, with a total of eight injections). The total levels of the investigated MAPKs and the phospho-p38(MAPK) in the neocortex and hippocampus were not affected by the PTZ injections. The MAPKs phosphorylation levels remain unaltered in PTZ-treated animals without convulsive seizures. The phospho-JNK2 phosphorylation, but not the phospho-JNK1, was increased in the hippocampus of PTZ-treated animals showing 1-3 days with convulsive seizures, whereas no significant changes were observed in those animals with more than 3 days with convulsive seizures. The phospho-ERK1/2 phosphorylation decreased in the neocortex and increased in the hippocampus of animals with 1-4 days with convulsive seizures and became unaltered in mice that showed convulsive seizures for more than 4 days. These findings indicate that resistance to PTZ kindling is associated with unaltered ERK1/2, JNK1/2 and p38(MAPK) phosphorylation levels in the neocortex and hippocampus. Moreover, when the PTZ kindling-induced epileptogenesis manifests behaviorally, the activation of the different MAPKs sub-families shows a variable and non-linear pattern in the neocortex and hippocampus.
Assuntos
Hipocampo/enzimologia , Excitação Neurológica/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neocórtex/enzimologia , Pentilenotetrazol/farmacologia , Animais , Masculino , CamundongosRESUMO
Agmatine, a cationic polyamine synthesized after decarboxylation of L-arginine by the enzyme arginine decarboxylase, is an endogenous neuromodulator that emerges as a potential agent to manage diverse central nervous system (CNS) disorders. Consistent with its neuromodulatory and neuroprotective properties, there is increasing number of preclinical studies demonstrating the beneficial effects of exogenous agmatine administration on depression, anxiety, hypoxic ischemia, nociception, morphine tolerance, memory, Parkinson`s disease, Alzheimer`s disease, traumatic brain injury related alterations/disorders and epilepsy. The aim of this review is to summarize the knowledge about the effects of agmatine in CNS and point out its potential as new pharmacological treatment for diverse neurological and neurodegenerative diseases. Moreover, some molecular mechanisms underlying the neuroprotective effects of agmatine will be discussed.
Assuntos
Agmatina/farmacologia , Antidepressivos/farmacologia , Lesões Encefálicas/tratamento farmacológico , Sistema Nervoso Central/metabolismo , Epilepsia/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Agmatina/administração & dosagem , Agmatina/uso terapêutico , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Humanos , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Lectins are proteins capable of reversible binding to the carbohydrates in glycoconjugates that can regulate many physiological and pathological events. Galectin-1, a ß-galactoside-binding lectin, is expressed in the central nervous system (CNS) and exhibits neuroprotective functions. Additionally, lectins isolated from plants have demonstrated beneficial action in the CNS. One example is a lectin with mannose-glucose affinity purified from Canavalia brasiliensis seeds, ConBr, which displays neuroprotective and antidepressant activity. On the other hand, the effects of the galactose-binding lectin isolated from Vatairea macrocarpa seeds (VML) on the CNS are largely unknown. The aim of this study was to verify if VML is able to alter neural function by evaluating signaling enzymes, glial and inflammatory proteins in adult mice hippocampus, as well as behavioral parameters. VML administered by intracerebroventricular (i.c.v) route increased the immobility time in the forced swimming test (FST) 60 min after its injection through a carbohydrate recognition domain-dependent mechanism. Furthermore, under the same conditions, VML caused an enhancement of COX-2, GFAP and S100B levels in mouse hippocampus. However, phosphorylation of Akt, GSK-3ß and mitogen-activated protein kinases named ERK1/2, JNK1/2/3 and p38(MAPK), was not changed by VML. The results reported here suggest that VML may trigger neuroinflammatory response in mouse hippocampus and exhibit a depressive-like activity. Taken together, our findings indicate a dual role for galactose binding lectins in the modulation of CNS function.
Assuntos
Depressão/induzido quimicamente , Fabaceae/química , Hipocampo/efeitos dos fármacos , Lectinas/farmacologia , Animais , Ciclo-Oxigenase 2/biossíntese , Galactose/farmacologia , Proteína Glial Fibrilar Ácida , Hipocampo/metabolismo , Injeções Intraventriculares , Lectinas/administração & dosagem , Masculino , Camundongos , Proteínas do Tecido Nervoso/biossíntese , Subunidade beta da Proteína Ligante de Cálcio S100/biossíntese , NataçãoRESUMO
Physical activity impacts functional recovery following stroke in humans, however its effects in experimental animals submitted to chronic cerebral hypoperfusion have not been investigated. The aim of this study was to evaluate the therapeutic potential of exercise, as assessed by cognitive activity in the Morris water maze and the brain oxidative status, through measurement of macromolecules damage, TBARS levels and total cellular thiols, as well as antioxidant enzymes in hippocampus, striatum and cerebral cortex. Adult male Wistar rats were submitted to the modified permanent bilateral occlusion of the common carotid arteries (2VO) method, with right common carotid artery being first occluded, and tested 3 months after the ischemic event. The effects of three different exercise protocols were examined: pre-ischemia, post-ischemia and pre+post-ischemia. Physical exercise consisted of sessions of 20-min, 3 times per week during 12 weeks (moderate intensity). Rats were submitted to cognitive assessment, in both reference and working spatial memory and after the last testing session were sacrificed to have oxidative stress parameters determined. Hypoperfusion caused a significant cognitive deficit in both spatial water maze tasks and this effect was reversed in rats receiving exercise protocol post and pre+post the ischemic event. Moreover, forced regular treadmill exercise regulated oxidative damage and antioxidant enzyme activity in the hippocampus. These results suggest that physical exercise protects against cognitive and biochemical impairments caused by chronic cerebral hypoperfusion.
Assuntos
Isquemia Encefálica/fisiopatologia , Hipocampo/irrigação sanguínea , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/prevenção & controle , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Isquemia Encefálica/complicações , Hipocampo/fisiopatologia , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Ratos , Ratos WistarRESUMO
Reduction of cerebral blood flow is an important risk factor for dementia states and other brain dysfunctions. In present study, the effects of permanent occlusion of common carotid arteries (2VO), a well established experimental model of brain ischemia, on memory function were investigated, as assessed by reference and working spatial memory protocols and the object recognition task; cell damage to the hippocampus, as measured through changes in immunoreactivity for GFAP and the neuronal marker NeuN was also studied. The working hypothesis is that metabolic impairment following hypoperfusion will affect neuron and glial function and result in functional damage. Adult male Wistar rats were submitted to the modified 2VO method, with the right common carotid artery being occluded first and the left one week later, and tested seven days, three and six months after the ischemic event. A significant cognitive deficit was found in both reference and working spatial memory, as well as in the object recognition task, three and six months after surgery. Neuronal death and reactive astrogliosis were already present at 7 days and continued for up to 3 months after the occlusion; interestingly, there was no significant reduction in hippocampal volume. Present data suggests that cognitive impairment caused by brain hypoperfusion is long - lasting and persists beyond the time point of recovery from glial activation and neuronal loss.
Assuntos
Encéfalo/anatomia & histologia , Morte Celular/fisiologia , Transtornos da Memória/fisiopatologia , Memória de Longo Prazo/fisiologia , Neuroglia/fisiologia , Neurônios/patologia , Animais , Comportamento Animal/fisiologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/fisiopatologia , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/patologia , Neuroglia/patologia , Neurônios/citologia , Ratos , Ratos WistarRESUMO
Several studies have shown that treadmill training improves neurological outcomes and promotes plasticity in lumbar spinal cord of spinal animals. The morphological and biochemical mechanisms underlying these phenomena remain unclear. The purpose of this study was to provide evidence of activity-dependent plasticity in spinal cord segment (L5) below a complete spinal cord transection (SCT) at T8-9 in rats in which the lower spinal cord segments have been fully separated from supraspinal control and that subsequently underwent treadmill step training. Five days after SCT, spinal animals started a step-training program on a treadmill with partial body weight support and manual step help. Hindlimb movements were evaluated over time and scored on the basis of the open-field BBB scale and were significantly improved at post-injury weeks 8 and 10 in trained spinal animals. Treadmill training also showed normalization of withdrawal reflex in trained spinal animals, which was significantly different from the untrained animals at post-injury weeks 8 and 10. Additionally, compared to controls, spinal rats had alpha motoneuronal soma size atrophy and reduced synaptophysin protein expression and Na(+), K(+)-ATPase activity in lumbar spinal cord. Step-trained rats had motoneuronal soma size, synaptophysin expression and Na(+), K(+)-ATPase activity similar to control animals. These findings suggest that treadmill step training can promote activity-dependent neural plasticity in lumbar spinal cord, which may lead to neurological improvements without supraspinal descending control after complete spinal cord injury.
Assuntos
Plasticidade Neuronal , Traumatismos da Medula Espinal/fisiopatologia , Sinapses/fisiologia , Caminhada , Animais , Western Blotting , Masculino , Ratos , Ratos WistarRESUMO
Since previous studies have shown that ovariectomy impairs memory and cognition, we investigated whether physical exercise would affect ovariectomy-induced memory deficits in inhibitory avoidance and Morris water maze tasks. Female adult Wistar rats were assigned to one of the following groups: sham (submitted to surgery without removal of the ovaries), exercise, ovariectomy (Ovx) and Ovx plus exercise. Thirty days after ovariectomy or sham surgery, animals were submitted to 1 month of treadmill exercise training for 20 min, three times per week. Rats were than tested in inhibitory avoidance and Morris water maze tasks in order to verify ovariectomy effects on aversive and spatial memory performance. Results show that ovariectomized rats were impaired in aversive memory and spatial navigation, both in reference and working memory protocols. Confirming the working hypothesis, ovariectomized rats submitted to exercise had those impairments prevented. These findings support that physical exercise might constitute an important strategy to minimize cognitive deficits found in post-menopausal women.
Assuntos
Aprendizagem da Esquiva/fisiologia , Aprendizagem em Labirinto/fisiologia , Condicionamento Físico Animal/fisiologia , Percepção Espacial/fisiologia , Comportamento Espacial/fisiologia , Análise de Variância , Animais , Feminino , Ovariectomia , Ratos , Ratos WistarRESUMO
Hormone deficiency following ovariectomy causes activation of Na(+),K(+)-ATPase and acetylcholinesterase (AChE) that has been related to cognitive deficits in experimental animals. Considering that physical exercise presents neuroprotector effects, we decide to investigate whether exercise training would affect enzyme activation in hippocampus and cerebral cortex, as well as adenosine nucleotide hydrolysis in synaptosomes from cerebral cortex of ovariectomized rats. Female adult Wistar rats were assigned to one of the following groups: sham (submitted to surgery without removal of the ovaries), exercise, ovariectomized (Ovx) and Ovx plus exercise. Thirty days after surgery, animals were submitted to one month of exercise training, three times per week. After, rats were euthanized, blood serum was collected and hippocampus and cerebral cortex were dissected. Data demonstrated that exercise reversed the activation of Na(+),K(+)-ATPase and AChE activities both in hippocampus and cerebral cortex of ovariectomized rats. Ovariectomy decreased AMP hydrolysis in cerebral cortex and did not alter adenine nucleotides hydrolysis in blood serum. Exercise per se decreased ADP and AMP hydrolysis in cerebral cortex. On the other hand, AMP hydrolysis in blood serum was increased by exercise in ovariectomized adult rats. Present data support that physical exercise might have beneficial effects and constitute a therapeutic alternative to hormone replacement therapy for estrogen deprivation.
Assuntos
Acetilcolinesterase/metabolismo , Nucleotídeos de Adenina/metabolismo , Condicionamento Físico Animal/fisiologia , Prosencéfalo/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Difosfato de Adenosina/metabolismo , Monofosfato de Adenosina/metabolismo , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/metabolismo , Regulação para Baixo/fisiologia , Ativação Enzimática/fisiologia , Estrogênios/deficiência , Ciclo Estral/fisiologia , Feminino , Hormônios Esteroides Gonadais/metabolismo , Hipocampo/anatomia & histologia , Hipocampo/metabolismo , Hidrólise , Ovariectomia , Ovário/metabolismo , Pós-Menopausa/fisiologia , Terminações Pré-Sinápticas/metabolismo , Prosencéfalo/anatomia & histologia , Ratos , Ratos WistarRESUMO
Since a previous study has shown that ovariectomy impairs spatial memory, we, herein, investigate the influence of pre- and post-treatment with a soy diet on the effects elicited by ovariectomy on spatial memory. In the pre-treatment, 20-day-old female Wistar rats were first fed for 60 days on a standard diet with casein (control) or a soy diet. At 80 days of age, the animals were assigned to one of the following groups: sham (submitted to surgery without removal of ovaries) and ovariectomized. One week after surgery, the rats were submitted to behavioral testing. In the post-treatment, 80-day-old female rats were assigned to one of the following groups: sham and ovariectomized. One week after surgery, animals were fed for 30 days with the same diet described above. Then, rats were submitted to water maze testing. Pre-treatment for two months before ovariectomy with the soy diet effectively prevented the increase in latency in finding the platform on the fifth day of training in the ovariectomized group. Ovariectomized rats subjected to soy diet post-treatment reversed the increase in latency to find the platform in the ovariectomized group on the fifth day of training and, the decrease in the time spent in target quadrant, the increase in the time spent in opposite quadrant and the latency to cross the platform location. Results show that both pre- and post-treatment protected against the impairment of memory, caused by ovariectomy. Post-treatment reversed various parameters of memory reference, indicating that post-treatment was more efficient than pre-treatment. Based on these findings, we suggest that soy diet (rich in isoflavones) may represent a novel therapeutic strategy to prevent or to treat cognitive symptoms found in some menopausal women.
Assuntos
Glycine max/química , Isoflavonas/uso terapêutico , Memória/efeitos dos fármacos , Memória/fisiologia , Ovariectomia/psicologia , Percepção Espacial/efeitos dos fármacos , Percepção Espacial/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The aim of this study was to investigate the effects of intrastriatal injection of hypoxanthine, the major compound accumulated in Lesch-Nyhan disease, on performance step-down inhibitory avoidance task in the rat. Male adult Wistar rats were divided in two groups: (1) saline-injected and (2) hypoxanthine-injected group. Treated-group received intrastriatal hypoxanthine solution 30 min before training session (memory acquisition) or immediately after training session (memory consolidation) or 30 before test session (memory retrieval) on step-down inhibitory avoidance task. Results show that hypoxanthine administration caused significant memory impairment in all periods tested. These results show that intrastriatal hypoxanthine administration provoked memory process impairment of step-down inhibitory avoidance task, an effect that might be related to the cognitive memory alterations in Lesch-Nyhan patients.