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1.
J Agric Food Chem ; 68(1): 206-212, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31808686

RESUMO

The present study aimed to investigate the effects of matured hop bitter acids (MHBAs) on human cognition, mental fatigue, and mood state. In this randomized double-blind placebo-controlled study, 60 healthy adults (age 45-64 years) with self-awareness of cognitive decline were randomly divided into 2 groups and received either orally administered MHBAs (35 mg/day) or placebo for 12 weeks. Cognitive functions and mental states were assessed using neuropsychological tests or questionnaires at baseline and weeks 6 and 12 of the intervention. The change in verbal fluency score at week 6 compared with that at baseline was significantly higher in the MHBAs-treated group compared with that in the placebo group (P = 0.034), and Stroop test score at week 12 was significantly lower in the MHBAs-treated group compared with the placebo group (P = 0.019). Furthermore, subjective fatigue and anxiety at week 12 were significantly improved in the MHBAs-treated group (P = 0.008 and 0.043, respectively) compared with the placebo group. This is the first study to evaluate the effects of bitter ingredients in beer on cognition, subjective mood, and mental fatigue in a clinical trial. Our findings suggest that hop-derived bitter acids might be beneficial for cognition and mood state.


Assuntos
Ácidos/metabolismo , Cerveja/análise , Cognição , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/psicologia , Humulus/química , Humulus/metabolismo , Extratos Vegetais/metabolismo , Ácidos/análise , Afeto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
2.
Braz J Med Biol Res ; 52(11): e8371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721903

RESUMO

Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain unknown. In this study, 3-month-old male Sprague-Dawley rats with permanent bilateral common carotid artery occlusion-induced VaD were treated orally with low (100 mg/kg) or high (200 mg/kg) dose ORC once a day for 4 weeks. The results of the Morris water maze test and Nissl staining showed that ORC treatment significantly alleviated learning and memory deficits and neuronal damage in rats with VaD. Mechanistically, the protein levels of a panel of genes associated with neuronal apoptosis (Bcl-2, Bax) and autophagy (microtubule-associated protein 1 chain 3, Beclin1, p62) were significantly altered by ORC treatment compared with VaD, suggesting a protective role of ORC against VaD-induced neuronal apoptosis and autophagy. Moreover, the Akt/mTOR pathway, which is known to be the upstream signaling governing apoptosis and autophagy, was found to be activated in ORC-treated rats, suggesting an involvement of Akt/mTOR activation in ORC-rendered protection in VaD rats. Taken together, this study demonstrated that ORC may alleviate learning and memory impairments and neuronal damage in VaD rats by altering the expression of apoptosis/autophagy-related genes and activation of the Akt/mTOR signaling pathway in neurons.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirrolidinas/administração & dosagem , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Demência Vascular/metabolismo , Demência Vascular/fisiopatologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
3.
Medicine (Baltimore) ; 98(48): e18189, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770275

RESUMO

Sparse is the research on the relationship between iron metabolism and mild cognitive impairment (MCI) in adults aged over 60 years with non-alcoholic fatty liver disease (NAFLD). The soluble transferrin receptor (sTfR), serum iron (SI), serum ferritin (SF), transferrin (TRF) and hemoglobin (HB) are indicators of iron metabolism.This study examined whether iron metabolism is associated with cognitive impairment in older individuals.A cross-sectional study was held in patients from a Chinese center. Individuals with NAFLD aged over 60 years were included if they did not have excessive alcohol intake and were free of stroke or dementia. Their cognitive function was assessed by the same neurologist. 3.0T H proton magnetic resonance spectroscopy (H-MRS) was performed to evaluate the hippocampus of the participants without contraindication. t test and Chi-square test were used to analyze the data. Binary logistic regression was used for correlation analysis.Fifty four (54%) of participants were diagnosed with MCI by the psychiatrist. MCI was significantly associated with higher sTfR after adjustment of all the covariates (OR = 2.565, 95%CI: 1.334∼4.934; P = .005). No statistically significant associations were observed between MCI and age or blood glucose or choline (Cho) /creatine (Cr) of theright hippocampus head.Increased age and low levels of sTfR and HB were associated with MCI in NAFLD individuals aged over 60 years.


Assuntos
Disfunção Cognitiva , Hemoglobinas/análise , Hipocampo/diagnóstico por imagem , Ferro , Hepatopatia Gordurosa não Alcoólica , Receptores da Transferrina/sangue , Idoso , China/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/metabolismo , Correlação de Dados , Estudos Transversais , Feminino , Ferritinas/análise , Humanos , Ferro/sangue , Ferro/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/psicologia , Transferrina/análise
4.
Medicine (Baltimore) ; 98(45): e17824, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702636

RESUMO

The hippocampus is one of the earliest sites involved in the pathology of Alzheimer's disease (AD). Therefore, we specifically investigated the sensitivity and specificity of hippocampal volume and glucose metabolism in patients being evaluated for AD, using automated quantitative tools (NeuroQuant - magnetic resonance imaging [MRI] and Scenium - positron emission tomography [PET]) and clinical evaluation.This retrospective study included adult patients over the age of 45 years with suspected AD, who had undergone fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) and MRI. FDG-PET-CT images were analyzed both qualitatively and quantitatively. In quantitative volumetric MRI analysis, the percentage of the total intracranial volume of each brain region, as well as the total hippocampal volume, were considered in comparison to an age-adjusted percentile. The remaining brain regions were compared between groups according to the final diagnosis.Thirty-eight patients were included in this study. After a mean follow-up period of 23 ±â€Š11 months, the final diagnosis for 16 patients was AD or high-risk mild cognitive impairment (MCI). Out of the 16 patients, 8 patients were women, and the average age of all patients was 69.38 ±â€Š10.98 years. Among the remaining 22 patients enrolled in the study, 14 were women, and the average age was 67.50 ±â€Š11.60 years; a diagnosis of AD was initially excluded, but the patients may have low-risk MCI. Qualitative FDG-PET-CT analysis showed greater accuracy (0.87), sensitivity (0.76), and negative predictive value (0.77), when compared to quantitative PET analysis, hippocampal MRI volumetry, and specificity. The positive predictive value of FDG-PET-CT was similar to the MRI value.The performance of FDG-PET-CT qualitative analysis was significantly more effective compared to MRI volumetry. At least in part, this observation could corroborate the sequential hypothesis of AD pathophysiology, which posits that functional changes (synaptic dysfunction) precede structural changes (atrophy).


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Hipocampo/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/metabolismo , Diagnóstico Precoce , Feminino , Glucose/metabolismo , Hipocampo/metabolismo , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Sensibilidade e Especificidade
5.
Clin Interv Aging ; 14: 1631-1642, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571843

RESUMO

Purpose: Recent studies have found associations of increased brain amyloid beta (Aß) accumulation and several abnormal sleep-wake patterns, including shorter latency and increased fragmentation in preclinical Alzheimer's disease (AD). There is little known about the relationship between sleep and tau. The objective of this study was to understand the associations of both tau and Aß with early signs of sleep and night-time behavior changes in clinically normal elderly adults. Specifically, we have addressed the question of how informant-based subjective sleep reports are linked to regional [18F]flortaucipir and [18F]florbetapir uptake. Methods: Imaging and behavioral data from 35 subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative. The Neuropsychiatric Inventory Sleep (NPI-sleep) Questionnaire was used to assess the sleep and night-time behavior changes. Regional tau-positron emission tomography (PET) (entorhinal, brainstem) and Aß-PET (posterior cingulate, precuneus, medial orbitofrontal) uptake values were calculated. A series of linear regression analyses were used to determine the combination of sleep symptoms that built the best models to predict each pathology. Results: Informant-based reports of abnormal night-time behavior (NPI questions k3, k5, and k8) were significantly associated with increased entorhinal tau and Aß (all regions) accumulation. Interestingly, informant-based reports of sleep deficiencies without abnormal nigh-time activity (NPI questions k1, k2, and k6) were negatively associated with entorhinal tau burden. Conclusion: Detection of abnormal night-time behaviors (wandering, pacing, other inappropriate activities) by family members indicates early signs of both AD pathologies and may encourage the affected individuals to seek help by health care providers for detailed cognitive/neurobehavioral assessments.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Córtex Entorrinal/metabolismo , Sono , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Compostos de Anilina , Sintomas Comportamentais , Carbolinas , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Córtex Entorrinal/diagnóstico por imagem , Etilenoglicóis , Feminino , Humanos , Masculino , Neuroimagem , Tomografia por Emissão de Pósitrons/métodos , Inquéritos e Questionários , Fatores de Tempo
6.
Life Sci ; 236: 116867, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31520598

RESUMO

AIM: Cyclophosphamide (CP) is a potent anticancer and immunosuppressant drug. Studies have shown significant oxidative stress and cognitive impairment but neuroinflammatory and histological aberrations with its administration is underexplored. Nerolidol (NER) is a lipophilic bioactive molecule with antioxidant and anti-inflammatory properties but it has not been explored for neuroprotective potential in CP-induced neurotoxic manifestations. Therefore, in the present study, we aimed to evaluate the neuroprotective potential of NER in CP-induced neuroinflammation and associated comorbid conditions like depression and cognitive dysfunctions. MATERIALS AND METHOD: In-silico study using Schrödinger software was used to assess the binding affinity of NER with Nrf2. In the In vivo study, NER 200 and 400 mg/kg p.o. were given from 1st day to 14th day. CP 200 mg/kg, i.p., was administered on the 7th day. After 24 h of the last dosing, neurobehavioral tests like spontaneous body alternation, passive avoidance and forced swim test were performed. On completion of study, mice were sacrificed, hippocampus and cortex were removed for biochemical estimations, histopathology and immunohistochemistry of p65 NF- κB and Nrf2. KEY FINDINGS: In-silico study showed significant binding of NER into the pocket domain of Nrf2. In-vivo study showed protective effect of NER against CP-induced neuroinflammation, oxidative stress, cognitive impairment and structural abnormalities in the hippocampus and cortex regions. SIGNIFICANCE: Findings of the study suggested that NER is a potential therapeutic molecule which can mitigate CP-induced neurotoxic manifestations via Nrf2 and NF-κB pathway. However, more detailed studies are needed to explicate the mechanism underlying its neuroprotective effect.


Assuntos
Disfunção Cognitiva/prevenção & controle , Ciclofosfamida/toxicidade , Inflamação/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Regulação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imunossupressores/toxicidade , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Fármacos Neuroprotetores , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Transdução de Sinais
7.
Int J Mol Sci ; 20(18)2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505809

RESUMO

Many neurodegenerative disorders have lysosomal impediments, and the list of proposed treatments targeting lysosomes is growing. We investigated the role of lysosomes in Alzheimer's disease (AD) and other age-related disorders, as well as in a strategy to compensate for lysosomal disturbances. Comprehensive immunostaining was used to analyze brains from wild-type mice vs. amyloid precursor protein/presenilin-1 (APP/PS1) mice that express mutant proteins linked to familial AD. Also, lysosomal modulation was evaluated for inducing synaptic and behavioral improvements in transgenic models of AD and Parkinson's disease, and in models of mild cognitive impairment (MCI). Amyloid plaques were surrounded by swollen organelles positive for the lysosome-associated membrane protein 1 (LAMP1) in the APP/PS1 cortex and hippocampus, regions with robust synaptic deterioration. Within neurons, lysosomes contain the amyloid ß 42 (Aß42) degradation product Aß38, and this indicator of Aß42 detoxification was augmented by Z-Phe-Ala-diazomethylketone (PADK; also known as ZFAD) as it enhanced the lysosomal hydrolase cathepsin B (CatB). PADK promoted Aß42 colocalization with CatB in lysosomes that formed clusters in neurons, while reducing Aß deposits as well. PADK also reduced amyloidogenic peptides and α-synuclein in correspondence with restored synaptic markers, and both synaptic and cognitive measures were improved in the APP/PS1 and MCI models. These findings indicate that lysosomal perturbation contributes to synaptic and cognitive decay, whereas safely enhancing protein clearance through modulated CatB ameliorates the compromised synapses and cognition, thus supporting early CatB upregulation as a disease-modifying therapy that may also slow the MCI to dementia continuum.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Lisossomos/metabolismo , Doença de Parkinson/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/patologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Humanos , Glicoproteínas de Membrana Associadas ao Lisossomo/genética , Glicoproteínas de Membrana Associadas ao Lisossomo/metabolismo , Lisossomos/genética , Lisossomos/patologia , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/patologia , Doença de Parkinson/genética , Doença de Parkinson/patologia , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Sinapses/metabolismo , Sinapses/patologia
9.
Postgrad Med ; 131(7): 501-508, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31483196

RESUMO

Objectives: Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) is a longitudinal ongoing study initiated in 2018 that takes place in the Cognitive Disorders Clinic of Aiginition Hospital of the National and Kapodistrian University of Athens. Its aim is to address several research questions concerning the preclinical and prodromal stage of Alzheimer's disease and explore potential markers for early detection, prediction, and primary prevention of dementia. Methods: We here present the design and the preliminary baseline characteristics of ALBION. The sample of our study consists of people aged over 50 who are concerned about their memory but are cognitively normal (CN) or have mild cognitive deficits. Each participant undergoes an extensive assessment including several demographic, medical, social, environmental, clinical, nutritional, neuropsychological determinants and lifestyle activities. Furthermore, we are collecting data from portable devices, neuroimaging techniques and biological samples (blood, stools, CSF). All participants are assessed annually for a period of 10 years. Results: In total, 47 participants have completed the initial evaluation up to date and are divided in two groups, CN individuals (N = 26) and MCI patients (N = 21), based on their cognitive status. The participants are, on average, 64 years old, 46.3% of the sample is male with an average of 12.73 years of education. MCI patients report more comorbidities and have a lower score in the MMSE test. Regarding APOE status, 2 participants are ε4 homozygotes and 10 ε4 heterozygotes. CSF analyses (Aß42, Τ-tau, P-tau) revealed no differences between the two groups. Conclusion: The ALBION study offers an opportunity to explore preclinical dementia and identify new and tailored markers, particularly relating to lifestyle. Further investigation of these populations may provide a wider profile of the changes taking place in the preclinical phase of dementia, leading to potentially effective therapeutic and preventive strategies.


Assuntos
Doença de Alzheimer/prevenção & controle , Disfunção Cognitiva/metabolismo , Prevenção Primária , Sintomas Prodrômicos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteínas E/genética , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Diagnóstico Precoce , Eletroencefalografia , Feminino , Neuroimagem Funcional , Grécia , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano , Dados Preliminares , Proteínas tau/líquido cefalorraquidiano
10.
Life Sci ; 235: 116822, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31476310

RESUMO

AIMS: To investigate the effects of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) on cognitive dysfunction, the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and amyloid ß peptide (Aß) in the hippocampus, as well as dendritic pathology in the hippocampal CA1 region in sepsis-associated encephalopathy (SAE) rats. MAIN METHODS: The rats were randomly divided into four groups: 1) control group (subjected to sham surgery), 2) control plus Mfhas1 siRNA group (rats received intracerebroventricular injection of Mfhas1 siRNA after sham surgery), 3) CLP plus control siRNA group (rats received intracerebroventricular injection of control siRNA after cecal ligation and puncture (CLP)), 4) CLP plus Mfhas1 siRNA group (rats received intracerebroventricular injection of Mfhas1 siRNA after CLP). The learning and memory capabilities of the rats were examined by means of fear conditioning and Barnes maze test. The concentration of TNF-α and IL-1ß was determined by enzyme-linked immunosorbent assay. The efficiency of siRNA transfection, MFHAS1 and Aß expression were detected by Western blotting. Total branch lengths of pyramidal dendrites of the CA1 basilar trees and spine density were determined by Golgi staining. KEY FINDINGS: We observed that MFHAS1 knock-down by Mfhas1 siRNA intracerebroventricular injection could improve cognitive impairment, reduce the expression of TNF-α, IL-1ß and Aß in the hippocampus induced by CLP, and alleviate the dendritic spinal loss of the pyramidal neurons, as well as increase the dendritic branching of the CA1 basilar trees of septic rats. SIGNIFICANCE: MFHAS1 knock-down can alleviate cognitive impairment, neuroinflammation and dendritic spinal loss in SAE rats.


Assuntos
Disfunção Cognitiva/prevenção & controle , Dendritos/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Proteínas Oncogênicas/antagonistas & inibidores , RNA Interferente Pequeno/administração & dosagem , Encefalopatia Associada a Sepse/complicações , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Dendritos/metabolismo , Dendritos/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , RNA Interferente Pequeno/genética , Ratos , Ratos Wistar
11.
J Stroke Cerebrovasc Dis ; 28(10): 104299, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31371141

RESUMO

Cognitive dysfunction is the most common nonphysical impairment in the stroke survivors. This impairment has a negative impact on patients' quality of life affects their daily living activities. Both pharmacological and nonpharmacological interventions are employed to improve cognitive impairment. Recently, nonpharmacological interventions have attracted great attention. Cognitive rehabilitation is considered as a therapeutic strategy to improve and maintain cognitive skills in patients with stroke. Enriched environment (EE), as a cognitive rehabilitation strategy, has been shown to facilitate physical, cognitive, as well as social abilities. Moreover, EE has been shown to increase endogenous growth factors. Growth factors have pivotal role in neurogenesis, synaptogenesis, as well as brain remodeling through neuron development, differentiation, and survival. In addition, administration of exogenous growth factors prevents cognitive dysfunction. Here, we review preclinical and clinical evidence of cognitive rehabilitation and role of growth factors in treating poststroke cognitive impairment.


Assuntos
Isquemia Encefálica/reabilitação , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Terapia Cognitivo-Comportamental , Disfunção Cognitiva/reabilitação , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/psicologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Resultado do Tratamento
12.
Life Sci ; 234: 116775, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31425697

RESUMO

AIMS: The activation of the angiotensin (Ang) II after acute kidney injury (AKI) triggers oxidative stress and inflammatory cascade which involved not only the kidneys but also the brain. Ang II through the Ang II type 1 receptor (AT1R) may have deleterious effects on hippocampal synaptic transmission and cognitive functions under uremic encephalopathy. The present study was conducted to examine the effects of AT1R antagonist on AKI-induced cognitive and synaptic plasticity impairment. MAIN METHODS: Here, we investigated the effect of AKI and possible pathophysiological roles of AT1R with the selective AT1R antagonist losartan (10 mg/kg/day for consecutive 9 days) on cognitive performance using passive avoidance and Morris water maze tests. In order to understand the synaptic transmission, in vivo short and long-term plasticity were evaluated at the Schaffer collateral-CA1 synapse. Biochemical analysis was also performed to detect possible hippocampal nitric oxide and oxidative stress mechanisms. KEY FINDINGS: Our data provide evidence of hippocampal complication following AKI with increased level of nitrite (P < 0.01 vs. sham) as well as oxidative stress (P < 0.01 vs. sham) that may be responsible for behavioral dysfunction under uremia (spatial memory, P < 0.001; passive avoidance P < 0.01 vs. sham). Losartan treatment effectively protects against cognitive (spatial memory, P < 0.01; passive avoidance P < 0.05 vs. AKI-veh) and synaptic plasticity impairments induced by AKI possibly via modulation of oxidative stress in the hippocampus (P < 0.01 vs. AKI-veh). SIGNIFICANCE: The present study conclusively demonstrated a protective role of AT1R antagonist losartan in hippocampal complication and neurocognitive dysfunction after AKI via modulating oxidative stress.


Assuntos
Lesão Renal Aguda/complicações , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Hipocampo/efeitos dos fármacos , Losartan/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/fisiopatologia , Animais , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Memória/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo
13.
Int J Mol Sci ; 20(17)2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31450692

RESUMO

Mild cognitive impairment (MCI) is characterized by a level of cognitive impairment that is lower than normal for a person's age, but a higher function than that that observed in a demented person. MCI represents a transitional state between normal aging and dementia disorders, especially Alzheimer's disease (AD). Much effort has been made towards determining the prognosis of a person with MCI who will convert to AD. It is now clear that cerebrospinal fluid (CSF) levels of Aß40, Aß42, total tau and phosphorylated tau are useful for predicting the risk of progression from MCI to AD. This review highlights the advantages of the current blood-based biomarkers in MCI, and discusses some of these challenges, with an emphasis on recent studies to provide an overview of the current state of MCI.


Assuntos
Biomarcadores , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/metabolismo , Animais , Atrofia , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Encéfalo/metabolismo , Encéfalo/patologia , MicroRNA Circulante , Disfunção Cognitiva/etiologia , Diagnóstico Diferencial , Progressão da Doença , Humanos , MicroRNAs/genética , Prognóstico
14.
Artigo em Inglês | MEDLINE | ID: mdl-31326961

RESUMO

Background Natural medicinal plants have been the focus of current research for developing neuroprotective agents to be used in the diabetes-linked cognitive dysfunction. Trigonella foenum-graecum seeds (known as fenugreek, methi in Hindi), is a well-known traditional medicinal herb and possesses anti-diabetic, anti-oxidant, and anti-inflammatory properties. Purpose This study was undertaken to explore the ameliorative effects of T. foenum-graecum seed extract on diabetes-induced cognitive dysfunction. Methods Experimental diabetes was induced by administering a single dose of streptozotocin (60 mg/kg) through intraperitoneal dose. Cognitive function was assessed using a T-maze and the Morris water maze. Lipid peroxidation levels and oxidative stress in the hippocampus was measured. Quantification of hippocampal CA1 and CA3 regions was done using cresyl violet stain. Results Diabetic rats demonstrated learning and memory impairment, which was evident from poor performance in behavioral tasks, i.e. T-maze and Morris water maze tasks. Learning and memory impairment in diabetic animals is associated with increased blood glucose levels, increased oxidative stress in the hippocampus and decreased number of neurons in the CA1 and CA3 regions of the hippocampus. The diabetic rats administered with T. foenum-graecum showed improved performance in behavioral tasks, and these changes were associated with decreased blood glucose levels, decreased oxidative stress in the hippocampus, and decreased neuronal loss from the CA1 and CA3 regions of the hippocampus. Conclusion In conclusion, administration of T. foenum-graecum seed extract ameliorates diabetes-linked cognitive dysfunction in rats by decreasing blood glucose levels, reducing lipid peroxidation and oxidative stress in the hippocampus, and preventing neuronal loss from the hippocampus.


Assuntos
Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Extratos Vegetais/farmacologia , Estreptozocina/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Glicemia/efeitos dos fármacos , Disfunção Cognitiva/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hipoglicemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Trigonella/química
15.
Clin Interv Aging ; 14: 1167-1175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303750

RESUMO

Purpose: We assessed the effect of home-based cognitive intervention (HCI) on cognitive function along with brain metabolism by 18F-FDG PET in patients with amnestic MCI (aMCI). Patients and methods: Fifty-seven patients with aMCI from three hospitals were randomized (30 HCI, 27 control). For 12 weeks, subjects received HCI. Thirty-two subjects (15 HCI, 17 control) underwent brain 18-F-FDG-PET imaging at baseline and at 12 and 24 weeks. Results: The HCI group showed significant improvement in the scores of the Controlled Oral Word Association Test (COWAT) 12 and at 24 weeks. Significant brain metabolic changes by 18F-FDG PET were not observed. Conclusion: The current study suggests that HCI was effective in improving general cognition along with frontal executive function in patients with aMCI.


Assuntos
Cognição , Terapia Cognitivo-Comportamental/métodos , Disfunção Cognitiva/reabilitação , Idoso , Encéfalo/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Função Executiva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons/métodos , Resultado do Tratamento
16.
Phytomedicine ; 63: 153007, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301537

RESUMO

BACKGROUND: Aerial parts of Peganum harmala Linn is used as a traditional medical herb for treatment of amnesia in Uighur medicine in China. Deoxyvasicine (DVAS) is one of the chief active ingredients in P. harmala, it possesses strong acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in vitro, but the therapeutic effect and mechanisms on amnesia in vivo are unclear. PURPOSE: The objective of this study was to investigate the improvement effect of DVAS from P. harmala in learning and memory deficits of scopolamine-induced mice and elucidate the underlying mechanisms involved. METHODS: Mice were pretreated with DVAS (5, 15 and 45 mg/kg) and huperzine-A (0.2 mg/kg) by gavage for 7 days, and subsequently were daily intraperitoneally injected with scopolamine (1 mg/kg) to induce learning and memory deficits and behavioral performance was assessed by Morris water maze. To further evaluate the potential mechanisms of DVAS in improving learning and memory capabilities, pathological change, levels of various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation were examined. RESULTS: The results showed that DVAS could alleviate learning and memory deficits in scopolamine-treated mice. DVAS could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities and protein expressions. DVAS could induce brain-derived neurotrophic factor and protect hippocampal pyramidal cells against neuronal damage. DVAS also enhanced antioxidant defense via increasing the antioxidant enzyme level and activity of glutathione peroxidase, and anti-inflammatory function through suppressing tumor necrosis factor-α. Additionally, DVAS could regulate the neurotransmitters by elevating acetylcholine, 5-hydroxytryptamine, γ-aminobutyric acid and reducing 5-hydroxyindole-3-acetic acid and glutamic acid. CONCLUSION: Results illustrated that DVAS may be a promising candidate compound against amnesia via restoration of cholinergic function, regulating neurotransmitters, attenuating neuroinflammation and oxidative stress.


Assuntos
Alcaloides/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Quinazolinas/farmacologia , Acetilcolina/metabolismo , Amnésia/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Inibidores da Colinesterase/farmacologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peganum/química , Escopolamina/toxicidade , Sesquiterpenos/farmacologia
17.
Med Sci Monit ; 25: 4627-4638, 2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31266934

RESUMO

BACKGROUND Subclinical epileptiform discharges (SEDs) are defined as epileptiform electroencephalographic (EEG) discharges without clinical signs of seizure in patients. The subthreshold convulsant discharge (SCD) is a frequently used model for SEDs. This study aimed to investigate the effect of levetiracetam (LEV), an anti-convulsant drug, on cognitive impairment of SCD model rats and to assess the associated mechanisms. MATERIAL AND METHODS A SCD rat model was established. Rats were divided into an SCD group, an SCD+ sodium valproate (VPA) group, and an SCD+ levetiracetam (LEV) group. The Morris water maze was used to evaluate the capacity of positioning navigation and space exploration. The field excitatory post-synaptic potentials (fEPSPs) were evaluated using a bipolar stimulation electrode. NCAM, GAP43, PS95, and CaMK II levels were detected using Western blot and RT-PCR, respectively. PKC activity was examined by a non-radioactive method. RESULTS LEV shortens the latency of platform seeking in SCD rats in positioning navigation. fEPSP slopes were significantly lower in the SCD group, and LEV treatment significantly enhanced the fEPSP slopes compared to the SCD group (P<0.05). The NCAM and GAP-43 levels were increased and PSD-95 levels were increased in SCD rats (P<0.05), which were improved by LEV treatment. The PKC activity and CaMK II levels were decreased in SCD rats and LEV treatment significantly enhanced PKC activity and increased CaMK II levels. CONCLUSIONS Cognitive impairment in of SCD model rats may be caused by decreased PKC activity, low expression of CaMK II, and inhibition of LTP formation. LEV can improve cognitive function by activating the PKC-GAP-43-CaMK signal transduction pathway.


Assuntos
Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Levetiracetam/farmacologia , Animais , Proteínas Quinases Dependentes de Cálcio-Calmodulina/efeitos dos fármacos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Eletroencefalografia , Proteína GAP-43/efeitos dos fármacos , Proteína GAP-43/metabolismo , Hipocampo/metabolismo , Levetiracetam/metabolismo , Masculino , Fosforilação , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Convulsões/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Ácido Valproico/uso terapêutico
18.
J Clin Neurosci ; 67: 210-214, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31288981

RESUMO

The aim of this study was to explore the differences in cognitive and neurological functions between cerebral small vessel disease (CSVD) rats and normal rats, as well as to study the Toll- like receptor 4 (TLR4) expression in the hippocampus of CSVD rats to understand its role in this brain structure. Forty male, 12-week old, specific pathogen-free (SPF), spontaneously hypertensive rats (SHRs) were used as the observation group, while 20 12-week old, SPF, Wistar male rats were used as the control group. After each measurement, 10 rats in the observation group and 5 in the control group were decapitated to collect samples for determining the expression of TLR4 in the hippocampus. At T1, difference in the latency of rats in the observation group showed no statistically significance (p = 0.836), while at T2, T3 and T4, the observation group showed longer latency than did the control group (p < 0.001). In addition, the latency of SHRs at T1 was the shortest (p < 0.05) compared to the follow-ups (T2-T4) and were followed sequentially by T2, T3, and T4 (p < 0.05). The latency was shorter than those at T1 and T2, and the shortest latency was found at T4 (p < 0.05). CSVD rats exhibited poor cognitive and neurological functions compared to normal rats and high expression of TLR4 in the hippocampus. Based on these results, we suggest that TLR4 affects the cognitive function of CSVD rats, and, thus, may be a valuable target in the treatment of CSVD.


Assuntos
Doenças de Pequenos Vasos Cerebrais/metabolismo , Disfunção Cognitiva/metabolismo , Receptor 4 Toll-Like/biossíntese , Animais , Doenças de Pequenos Vasos Cerebrais/complicações , Disfunção Cognitiva/etiologia , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Wistar
19.
Artigo em Inglês | MEDLINE | ID: mdl-31195602

RESUMO

Abnormal cerebrospinal fluid (CSF) levels of ß-amyloid peptides (Aß42) and Tau and cognitive decline are typical characteristics of Alzheimer's disease (AD). Since dysregulation in lipid metabolism accompanies abnormal amyloid formation, we quantified glycerophospholipids (GP) and sphingolipids (SP) in CSF fractions from participants with late-onset AD (LOAD, n = 29) or with Other Dementia (OD, n = 10) to determine if alterations in lipid metabolism account for pathological differences. Aß42 and total Tau levels were determined using a sandwich ELISA. Liposomal-based fluorescent assays were used to measure phospholipase A2 (PLA2) and acid or neutral sphingomyelinase (aSMase, nSMase) activities. Supernatant fluid (SF) and nanoparticle (NP) lipids were quantified using LC-MS/MS. Although CSF Aß42 and Tau levels are similar, phosphatidylserine (PS) in SF and ceramide (CM) levels in NP are significantly higher in OD compared with LOAD. The aSMase but not the nSMase activity is higher in OD. PLA2 activity in CSF from OD subjects positively correlates with several GP classes in SF and NP fractions but not in LOAD fractions. Our data indicate differences in CSF lipid metabolism between dementia variants. Higher levels of inflammatory and apoptotic lipids may induce faster neuronal death, resulting in the earlier cognitive decline in patients with OD phenotypes.


Assuntos
Disfunção Cognitiva/metabolismo , Demência/metabolismo , Transtornos de Início Tardio/metabolismo , Metabolismo dos Lipídeos , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Feminino , Humanos , Transtornos de Início Tardio/líquido cefalorraquidiano , Masculino , Fenótipo , Esfingomielina Fosfodiesterase/líquido cefalorraquidiano
20.
Nat Commun ; 10(1): 2353, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164641

RESUMO

The link between brain amyloid-ß (Aß), metabolism, and dementia symptoms remains a pressing question in Alzheimer's disease. Here, using positron emission tomography ([18F]florbetapir tracer for Aß and [18F]FDG tracer for glucose metabolism) with a novel analytical framework, we found that Aß aggregation within the brain's default mode network leads to regional hypometabolism in distant but functionally connected brain regions. Moreover, we found that an interaction between this hypometabolism with overlapping Aß aggregation is associated with subsequent cognitive decline. These results were also observed in transgenic Aß rats that do not form neurofibrillary tangles, which support these findings as an independent mechanism of cognitive deterioration. These results suggest a model in which distant Aß induces regional metabolic vulnerability, whereas the interaction between local Aß with a vulnerable environment drives the clinical progression of dementia.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Emaranhados Neurofibrilares/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina , Animais , Animais Geneticamente Modificados , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Etilenoglicóis , Fluordesoxiglucose F18 , Humanos , Imagem por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Ratos
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