RESUMO
OBJECTIVE: The present study was designed to test the hypothesis that there is a reduction in the activity of the enzyme cytochrome c oxidase (Cox) in Alzheimer's disease (AD). METHODS: Systematic review of literature and meta-analysis were used with data obtained from the PubMed, Scopus, MEDLINE, Lilacs, Eric and Cochrane. The keywords were Alzheimer's AND Cox AND mitochondria; Alzheimer's AND Cox AND mitochondria; Alzheimer's AND complex IV AND mitochondria. A total of 1372 articles were found, 23 of them fitting the inclusion criteria. The data were assembled in an Excel spreadsheet and analysed using the RevMan software. A random effects model was adopted to the estimative of the effect. RESULTS: The data shows a significant decrease in the activity of the Cox AD patients and animal models. CONCLUSION: Cox enzyme may be an important molecular component involved in the mechanisms underlying AD. Therefore, this enzyme may represent a possible new biomarker for the disease as a complementary diagnosis and a new treatment target for AD.
Assuntos
Doença de Alzheimer/enzimologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Mitocôndrias/enzimologia , Doença de Alzheimer/diagnóstico , Animais , Colorimetria/métodos , Humanos , Camundongos , Mitocôndrias/metabolismo , Modelos Animais , Polarografia/métodos , Ratos , Software , Espectrofotometria/métodosRESUMO
The links between spatial behavior and hippocampal levels of synapsin I and phosphosynapsin I were assessed in normal rats and in the pyrithiamine-induced thiamine deficiency (PTD) rat model of Wernicke-Korsakoff's syndrome. Synapsin I tethers small synaptic vesicles to the actin cytoskeleton in a phosphorylation-dependent manner, is involved in neurotransmitter release and has been implicated in hippocampal-dependent learning. Positive correlations between spontaneous alternation behavior and hippocampal levels of both synapsin I and phosphorylated synapsin I were found in control rats. However, spontaneous alternation performance was impaired in PTD rats and was accompanied by a significant reduction (30%) in phosphorylated synapsin I. Furthermore, no correlations were observed between either form of synapsin I and behavior in PTD rats. These data suggest that successful spontaneous alternation performance is related to high levels of hippocampal synapsin I and phosphorylated synapsin I. These results not only support the previous findings that implicate impaired hippocampal neurotransmission in the spatial learning and memory deficits associated with thiamine deficiency, but also suggest a presynaptic mechanism.
Assuntos
Hipocampo/metabolismo , Síndrome de Korsakoff/metabolismo , Comportamento Espacial/fisiologia , Sinapsinas/metabolismo , Deficiência de Tiamina/metabolismo , Animais , Modelos Animais de Doenças , Síndrome de Korsakoff/induzido quimicamente , Síndrome de Korsakoff/fisiopatologia , Aprendizagem em Labirinto/fisiologia , Fosforilação , Ratos , Deficiência de Tiamina/fisiopatologiaRESUMO
BACKGROUND: Psychiatric symptoms during pregnancy induce an increase in morbidity and also in the mortality levels among women and children. However, the real association between pregnancy and psychiatric disorders and the peculiarities of the phenomenology of symptoms in underprivileged countryside communities remain uncertain. OBJECTIVE: To verify the association between psychiatric disorder, symptoms, and pregnancy among women from a low-income countryside community and to determine the specific cutoff points for major depression diagnosis according to Beck Depression Inventory for the different trimesters of pregnancy in this population. METHODS: Ninety-four pregnant women and 38 healthy women from the Conceição do Mato Dentro health service, a rural low-income community in Brazil, participated in the present study. Psychiatric examination included a structured clinical interview for psychiatric disorders according to Mini International Neuropsychiatric Interview and psychometric scales such as the Yale-Brown Obsessive Scale, the Beck Depression Inventory, and the Hamilton Anxiety Scale. The cutoff points for Beck Depression Inventory were determined through the application of receiver operating characteristic curves considering the diagnosis of major depression according to Mini International Neuropsychiatric Interview. RESULTS: The pregnant women had a higher frequency of psychiatric disorders and depression and anxiety symptoms. All cutoff points of Beck Depression Inventory were equal or higher than 12 with high sensitivity and specificity. Although the modified cutoff was selected based on both high sensitivity and high specificity, they were lower than when the cutoff was applied to nonpregnant women. CONCLUSION: Pregnancy was associated with the occurrence of psychiatric disorders and depressive and anxiety symptoms. In comparison to the literature, the present results indicate that there are different cutoff points in the Beck Depression Inventory for pregnant women from different cultures and in different pregnancy trimesters.
RESUMO
We investigated age-related changes in learning and memory performance and behavioural extinction in the water maze; and in endogenous levels of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the neocortex, hippocampus, thalamus and dorsal raphe nucleus of Wistar rats. Another aim was to assess the correlation between behavioural and biochemical parameters, which were measured in rodents of two different ages: 5 months (adults) and 16 months (middle-aged). The middle-aged subjects succeeded in learning the behavioural task, albeit with significantly worse performance when compared to adult animals. Aging also had significant main effects on memory and extinction. An age-dependent decrease in 5-HIAA levels was observed in both hippocampus and dorsal raphe nucleus (DRN). The decrease in DRN 5-HIAA was paralleled by a decrease in 5-HIAA/5-HT ratio in this brain area, which was significantly correlated to the animals' spatial memory performance and behavioural extinction. In addition, using middle-aged rats, a 2x2 factorial study was carried out to examine the effects of food restriction and chronic ethanol consumption on rat's performance in a spatial behavioural task and on central serotonergic parameters. None of these two treatments had a significant effect on the behavioural and biochemical parameters assessed, with the exception of extinction index, which was significantly affected by ethanol consumption. Long-term ethanol ameliorated the impairment in behavioural flexibility caused by aging. In conclusion, long-term ethanol consumption may have a role in protecting against age-related deficit in behavioural extinction. Moreover, the present results also indicate that DRN serotonergic system is involved in spatial memory and behavioural extinction.
Assuntos
Envelhecimento/fisiologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Extinção Psicológica/fisiologia , Ácido Hidroxi-Indolacético/metabolismo , Núcleos da Rafe/metabolismo , Serotonina/metabolismo , Análise de Variância , Animais , Comportamento Animal , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Química Encefálica/efeitos dos fármacos , Depressores do Sistema Nervoso Central/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Etanol/administração & dosagem , Extinção Psicológica/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/fisiologia , Núcleos da Rafe/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Extensive work has been done regarding the impact of thiamine deprivation on the nervous system. In cardiac tissue, chronic thiamine deficiency is described to cause changes in the myocardium that can be associated with arrhythmias. However, compared with the brain, very little is known about the effects of thiamine deficiency on the heart. Thus this study was undertaken to explore whether thiamine deprivation has a role in cardiac arrhythmogenesis. We examined hearts isolated from thiamine-deprived and control rats. We measured heart rate, diastolic and systolic tension, and contraction and relaxation rates. Whole cell voltage clamp was performed in rat isolated cardiac myocytes to measure L-type Ca(2+) current. In addition, we investigated the global intracellular calcium transients by using confocal microscopy in the line-scan mode. The hearts from thiamine-deficient rats did not degenerate into ventricular fibrillation during 30 min of reperfusion after 15 min of coronary occlusion. The antiarrhythmogenic effects were characterized by the arrhythmia severity index. Our results suggest that hearts from thiamine-deficient rats did not experience irreversible arrhythmias. There was no change in L-type Ca(2+) current density. Inactivation kinetics of this current in Ca(2+)-buffered cells was retarded in thiamine-deficient cardiac myocytes. The global Ca(2+) release was significantly reduced in thiamine-deficient cardiac myocytes. The amplitude of caffeine-releasable Ca(2+) was lower in thiamine-deficient myocytes. In summary, we have found that thiamine deprivation attenuates the incidence and severity of postischemic arrhythmias, possibly through a mechanism involving a decrease in global Ca(2+) release.
Assuntos
Arritmias Cardíacas/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Deficiência de Tiamina/fisiopatologia , Tiamina/sangue , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/patologia , Traumatismo por Reperfusão Miocárdica/complicações , Traumatismo por Reperfusão Miocárdica/patologia , Ratos , Ratos Wistar , Deficiência de Tiamina/complicações , Deficiência de Tiamina/patologiaRESUMO
The effects of chronic ethanol and thiamine deficiency, alone or associated, on hippocampal protein phosphorylation profiles ranging in molecular weight from 30 to 250kDa molecular weight, in stimulated (high K(+) concentration) and unstimulated (basal) conditions were investigated. These treatments significantly changed the phosphorylation level of an 86kDa phosphoprotein. Thiamine deficiency, but not chronic ethanol, induced a decrease in a behavioural extinction index, which is significantly correlated to the phosphorylation level of the p86 protein. These data add to and extend previous findings by our laboratory implicating the involvement of hippocampal neurotransmission components in extinction of a behaviour which involves learning of environmental spatial cues.
Assuntos
Extinção Psicológica/fisiologia , Hipocampo/metabolismo , Síndrome de Korsakoff/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Depressores do Sistema Nervoso Central/farmacologia , Modelos Animais de Doenças , Etanol/farmacologia , Masculino , Fosforilação , Ratos , Ratos Wistar , Deficiência de Tiamina/metabolismoRESUMO
Using an animal model of Wernicke-Korsakoff syndrome, in which rats were submitted to a chronic ethanol treatment with or without a thiamine deficiency episode, the glutamate uptake in the prefrontal cortex and spatial memory aspects were studied. It was found that (i) thiamine deficiency, but not chronic ethanol consumption, induced a significant decrease of glutamate uptake; (ii) thiamine-deficient subjects showed an impaired performance in the water maze spatial memory test though these animals were able to learn the task during the acquisition. In spite of the fact that thiamine deficiency affects both glutamate uptake and spatial reference memory, there was no significant correlation between these two data. The present results show that, although prefrontal cortex is considered by some authors a not vulnerable area to lesions caused by thiamine deficiency, this vitamin deficiency does cause a neurochemistry dysfunction in that region.
Assuntos
Ácido Glutâmico/metabolismo , Aprendizagem em Labirinto , Transtornos da Memória/etiologia , Córtex Pré-Frontal/metabolismo , Deficiência de Tiamina/metabolismo , Animais , Etanol/farmacologia , Masculino , Ratos , Ratos Wistar , Percepção EspacialRESUMO
Chronic ethanol intake causes various types of neural damage and behavioral impairments, probably acting through oxidative stress and excitotoxicity, while dietary restriction is considered by some authors to protect the central nervous system from these kinds of damage. In the present study, a factorial experimental design was used to investigate the effects of chronic ethanol and dietary restriction treatments, associated or not, on Wistar rats' exploratory behavior, spatial memory aspects and cortical and hippocampal acetylcholinesterase (AChE) activity. Dietary restriction lasted for the whole experiment, while ethanol treatment lasted for only 3 weeks. Despite the short ethanol treatment duration, for two behavior categories assessed, moving and rearing, an interaction was observed between the effects of chronic ethanol and dietary restriction. There were no significant differences in AChE activities among the groups. Cerebellar neural nitric oxide synthase (nNOs) activity was measured as a first step to assess oxidative stress. Dietary restriction significantly reduced NO formation. The present results indicate that dietary restriction might exert a protective effect against chronic-ethanol-induced changes in exploratory behavior. It is hypothesized that the mechanisms underlying this protection can involve prevention of oxidative stress.
Assuntos
Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Comportamento Exploratório/efeitos dos fármacos , Privação de Alimentos , Acetilcolinesterase/metabolismo , Análise de Variância , Animais , Comportamento Animal , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Comportamento Exploratório/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Óxido Nítrico Sintase Tipo I/metabolismo , Ratos , Ratos Wistar , Espectrometria de Fluorescência/métodosRESUMO
This is a factorial (2 x 2 x 2) spatial memory and cholinergic parameters study in which the factors are chronic ethanol, thiamine deficiency and naivety in Morris water maze task. Both learning and retention of the spatial version of the water maze were assessed. To assess retrograde retention of spatial information, half of the rats were pre-trained on the maze before the treatment manipulations of pyrithiamine (PT)-induced thiamine deficiency and post-tested after treatment (pre-trained group). The other half of the animals was only trained after treatment to assess anterograde amnesia (post-trained group). Thiamine deficiency, associated to chronic ethanol treatment, had a significant deleterious effect on spatial memory performance of post-trained animals. The biochemical data revealed that chronic ethanol treatment reduced acetylcholinesterase (AChE) activity in the hippocampus while leaving the neocortex unchanged, whereas thiamine deficiency reduced both cortical and hippocampal AChE activity. Regarding basal and stimulated cortical acetylcholine (ACh) release, both chronic ethanol and thiamine deficiency treatments had significant main effects. Significant correlations were found between both cortical and hippocampal AChE activity and behaviour parameters for pre-trained but not for post-trained animals. Also for ACh release, the correlation found was significant only for pre-trained animals. These biochemical parameters were decreased by thiamine deficiency and chronic ethanol treatment, both in pre-trained and post-trained animals. But the correlation with the behavioural parameters was observed only for pre-trained animals, that is, those that were retrained and assessed for retrograde retention.
Assuntos
Acetilcolina/metabolismo , Síndrome de Korsakoff/metabolismo , Síndrome de Korsakoff/fisiopatologia , Aprendizagem/fisiologia , Percepção Espacial/fisiologia , Acetilcolinesterase/metabolismo , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Depressores do Sistema Nervoso Central , Dieta com Restrição de Proteínas/métodos , Modelos Animais de Doenças , Etanol , Extinção Psicológica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Técnicas In Vitro , Síndrome de Korsakoff/induzido quimicamente , Masculino , Espectrometria de Massas/métodos , Aprendizagem em Labirinto/fisiologia , Neocórtex/efeitos dos fármacos , Neocórtex/metabolismo , Potássio/farmacologia , Ratos , Tempo de Reação/efeitos dos fármacos , Retenção Psicológica/fisiologia , Estatística como Assunto , Deficiência de Tiamina/complicações , Deficiência de Tiamina/metabolismo , Deficiência de Tiamina/fisiopatologiaRESUMO
Abstract Twenty-eight Wistar rats treated orally with 20% ethanol solution, were divided into two groups: adult group (n = 19) and aged group (n = 9) consisting of animals aged 4 and 12 months, respectively, at the beginning of the treatment. Neurons from the basal nucleus region were counted and the percentage of choline acetyltransferase-immunoreactive cholinergic neurons was determined in adjacent sections. Acetylcholine release and choline-acetyltransferase activity in the cerebral cortex were assessed in the same animals. Nutritional parameters of the ethanol treated animals were monitored and found to be normal. Chronic exposure to ethanol did not result in global neuronal loss or loss of cholinergic neurons in the basal nucleus region. However, a greater expression of ChAT-immunoreactivity in the basal nucleus region and a tendency toward increased ChAT activity in the cerebral cortex of the control and treated aged animals, compared respectively to adult ones, were observed. These findings suggest adaptive changes of the aged rats in response to the possible cholinergic hypofunction, manifested as a decreased release of acetylcholine under stimulated conditions.