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1.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204250

RESUMO

Supplementation with anthocyanins, which are a type of flavonoids mainly found in various berries, is hypothesized to be a promising approach to lower the risk of developing cognitive decline. The aim of this systematic review was to provide a comprehensive overview of dietary intervention trials describing effects of berry anthocyanins on cognitive performance in humans, while also addressing potential underlying mechanisms. A total of 1197 articles were identified through a systematic search, and 49 studies reporting effects on cognitive performance (n = 18), vascular function (n = 22), or cardiometabolic risk markers (n = 32) were included. Significant improvements were observed on memory, while some of the studies also reported effects on attention and psychomotor speed or executive function. Vascular function markers such as brachial artery flow-mediated vasodilation were also affected and consistent evidence was provided for the beneficial effects of berry anthocyanins on endothelial function. Finally, studies reported improvements in blood pressure, but effects on metabolic risk markers (e.g. carbohydrate and lipid metabolism) were less consistent. In conclusion, this review provides evidence for the beneficial effects of berry anthocyanins on cognitive performance as memory improved. Whether observed anthocyanin-induced improvements in vascular function and blood pressure underlie beneficial effects on cognitive performance warrants further study.


Assuntos
Antocianinas/farmacologia , Biomarcadores , Vasos Sanguíneos/efeitos dos fármacos , Cognição/efeitos dos fármacos , Suplementos Nutricionais , Frutas/química , Antocianinas/administração & dosagem , Atenção/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Memória/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Análise de Onda de Pulso , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Medicine (Baltimore) ; 100(25): e26363, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160408

RESUMO

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia, which may lead to severe memory loss and other cognitive disorders. Yukmijihwang-tang (YMJ), a type of Korean traditional herbal medicine, has been shown to be effective against neurodegenerative diseases. Although a meta-analysis on the efficacy of YMJ on AD exists, the study had some limitations, and there have been several newly published studies assessing the effect of YMJ. Therefore, the purpose of this study is to evaluate the efficacy and safety of YMJ as a treatment for AD through a meta-analysis. METHODS: A systematic search of the following electronic databases will be conducted to identify eligible studies: MEDLINE (PubMed), Elsevier (EMBASE), The Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Korean Medical Database (KMBASE), Oriental Medicine Advanced Searching Integrated System (OASIS), Korean Traditional Knowledge Portal, Citation Information by NII (CiNii), China National Knowledge Infrastructure (CNKI). All randomized controlled trials assessing the efficacy and safety of YMJ on the symptoms of AD will be included. Two independent reviewers will perform article retrieval, deduplication, data screening, data extraction, quality evaluation, and data analyses using RevMan version 5.4. The Cochrane risk of bias tool will be used to assess the quality of the trials. RESULTS: This study will provide synthesis of the cognitive function measured with neuropsychological tests, behavioral and psychological symptoms of dementia (BPSD), and activities of daily living (ADL) measured using validated scales. The clinical effective rate and adverse events will also be analyzed to assess the efficacy and safety of YMJ for treating AD. CONCLUSION: This systematic review will provide evidence for the efficacy and safety of YMJ in AD. ETHICS AND DISSEMINATION: Ethical approval is not required because individual patient data will not be included in this study. The study findings will be disseminated through conference presentations.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Cognição/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Atividades Cotidianas , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Metanálise como Assunto , Testes Neuropsicológicos , Revisões Sistemáticas como Assunto , Resultado do Tratamento
3.
Int J Mol Sci ; 22(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069531

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease, and it manifests as progressive memory loss and cognitive decline. However, there are no effective therapies for AD, which is an urgent problem to solve. Evodiamine, one of the main bioactive ingredients of Evodia rutaecarpa, has been reported to ameliorate blood-brain barrier (BBB) permeability and improve cognitive impairment in ischemia and AD mouse models. However, whether evodiamine alleviates tauopathy remains unclear. This study aimed to examine whether evodiamine ameliorates tau phosphorylation and cognitive deficits in AD models. METHODS: A protein phosphatase 2A inhibitor, okadaic acid (OA), was used to induce tau phosphorylation to mimic AD-like models in neuronal cells. Protein expression and cell apoptosis were detected using Western blotting and flow cytometry, respectively. Spatial memory/cognition was assessed using water maze, passive avoidance tests, and magnetic resonance imaging assay in OA-induced mice models, and brain slices were evaluated further by immunohistochemistry. RESULTS: The results showed that evodiamine significantly reduced the expression of phosphor-tau, and further decreased tau aggregation and neuronal cell death in response to OA treatment. This inhibition was found to be via the inhibition of glycogen synthase kinase 3ß, cyclin-dependent kinase 5, and mitogen-activated protein kinase pathways. In vivo results indicated that evodiamine treatment ameliorated learning and memory impairments in mice, whereas Western blotting and immunohistochemical analysis of the mouse brain also confirmed the neuroprotective effects of evodiamine. CONCLUSIONS: Evodiamine can decrease the neurotoxicity of tau aggregation and exhibit a neuroprotective effect. Our results demonstrate that evodiamine has a therapeutic potential for AD treatment.


Assuntos
Quinazolinas/farmacologia , Tauopatias/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular , Cognição/efeitos dos fármacos , Cognição/fisiologia , Transtornos Cognitivos/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Ácido Okadáico/efeitos adversos , Ácido Okadáico/farmacologia , Fosforilação , Quinazolinas/metabolismo , Memória Espacial/efeitos dos fármacos , Proteínas tau/efeitos dos fármacos , Proteínas tau/metabolismo
4.
Nutrients ; 13(5)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067795

RESUMO

Matcha, a type of green tea, has a higher amino acid content than other types of tea. We previously examined the ability of matcha to improve cognitive function in older adults and determined that continuous matcha intake improves attention and executive function. This study aimed to compare the effects of matcha and caffeine and clarify the differences between these effects. The study was registered at the University Hospital Medical Information Network (UMIN000036578). The effect of single and continuous intake was compared, and the usefulness of continuous intake was evaluated under the stress condition. The Uchida-Kraepelin test (UKT) was used to induce mild acute stress, and the Cognitrax was used to evaluate cognitive function. A single dose of caffeine improved attentional function during or after stress loading. The reduced reaction time in the Cognitrax, observed following a single dose of matcha, was likely due to caffeine. The matcha group showed an increase in the amount of work after continuous intake, whereas the caffeine group only showed an increase in the amount of work for the UKT after a single dose. Ingesting matcha with caffeine improves both attention and work performance when suffering from psychological stress compared with caffeine alone.


Assuntos
Cafeína/administração & dosagem , Cognição/efeitos dos fármacos , Ingestão de Alimentos/psicologia , Estresse Psicológico/psicologia , Chá , Idoso , Atenção/efeitos dos fármacos , Método Duplo-Cego , Ingestão de Líquidos , Função Executiva/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Chá/química
5.
Molecules ; 26(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071665

RESUMO

Halogens have been reported to play a major role in the inhibition of monoamine oxidase (MAO), relating to diverse cognitive functions of the central nervous system. Pyrazoline/halogenated pyrazolines were investigated for their inhibitory activities against human monoamine oxidase-A and -B. Halogen substitutions on the phenyl ring located at the fifth position of pyrazoline showed potent MAO-B inhibition. Compound 3-(4-ethoxyphenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole (EH7) showed the highest potency against MAO-B with an IC50 value of 0.063 µM. The potencies against MAO-B were increased in the order of -F (in EH7) > -Cl (EH6) > -Br (EH8) > -H (EH1). The residual activities of most compounds for MAO-A were > 50% at 10 µM, except for EH7 and EH8 (IC50 = 8.38 and 4.31 µM, respectively). EH7 showed the highest selectivity index (SI) value of 133.0 for MAO-B, followed by EH6 at > 55.8. EH7 was a reversible and competitive inhibitor of MAO-B in kinetic and reversibility experiments with a Ki value of 0.034 ± 0.0067 µM. The molecular dynamics study documented that EH7 had a good binding affinity and motional movement within the active site with high stability. It was observed by MM-PBSA that the chirality had little effect on the overall binding of EH7 to MAO-B. Thus, EH7 can be employed for the development of lead molecules for the treatment of various neurodegenerative disorders.


Assuntos
Simulação de Dinâmica Molecular , Inibidores da Monoaminoxidase/química , Pirazóis/química , Barreira Hematoencefálica/efeitos dos fármacos , Domínio Catalítico , Química Farmacêutica/métodos , Cognição/efeitos dos fármacos , Desenho de Fármacos , Halogênios/química , Humanos , Concentração Inibidora 50 , Cinética , Modelos Químicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Monoaminoxidase/metabolismo , Movimento (Física) , Análise de Componente Principal , Ligação Proteica , Proteínas Recombinantes/química , Estereoisomerismo , Relação Estrutura-Atividade
6.
Toxicol Lett ; 349: 101-108, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34147607

RESUMO

BACKGROUND: From 2012 to 2013, there was a mass methanol poisoning outbreak in the Czech Republic. Methanol metabolites can cause specific lesions in the basal ganglia, subcortical white matter, and optic nerve. However, long-term sequelae of methanol poisoning on cognitive functioning have not yet been explored. The current study aimed to delineate the cognitive changes observed in methanol poisoning survivors in the seven years since 2012. METHODS: We conducted longitudinal research with repeated measurements in 2013, 2015, 2017 and 2019 to evaluate the development of cognitive changes after acute methanol poisoning. A complex neuropsychological battery consisted of tests of global cognitive performance, auditory and visual attention, executive functioning, learning and memory, working memory and language. Motor performance measures and depression scale were also included. RESULTS: Repeated measures ANOVA of four measurements with post-hoc tests showed a significant decline in the Mini-Mental State Examination (p = 0.007); however, other parameters were not significantly decreasing. In comparison to normative values, the z-scores for each test measure, in the memory domain, in particular, ranged from 43 to 60 % of participants below 1.5 SD. Mild to severe depression levels from the onset of poisoning improved during the seven years, returning to normal in up to 27 % of participants. CONCLUSION: In the longitudinal perspective, methanol poisoning survivors manifest progressive global cognitive decline and overall persistent below-average cognitive performance with some improvements in the frequency of depressive symptoms.


Assuntos
Cognição/efeitos dos fármacos , Disfunção Cognitiva/psicologia , Depressão/psicologia , Transtornos da Memória/psicologia , Memória Episódica , Metanol/envenenamento , Síndromes Neurotóxicas/psicologia , Adulto , Idoso , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , República Tcheca/epidemiologia , Depressão/induzido quimicamente , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/diagnóstico , Transtornos da Memória/epidemiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/epidemiologia , Prevalência , Fatores de Tempo , Adulto Jovem
7.
Aging (Albany NY) ; 13(11): 15620-15637, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34106880

RESUMO

Amyloid ß (Aß) plays a major role in the neurodegeneration of Alzheimer's disease (AD). The accumulation of misfolded Aß causes oxidative stress and inflammatory damage leading to apoptotic cell death. Traditional Chinese herbal medicine (CHM) has been widely used in treating neurodegenerative diseases by reducing oxidative stress and neuroinflammation. We examined the neuroprotective effect of formulated CHM Shaoyao Gancao Tang (SG-Tang, made of Paeonia lactiflora and Glycyrrhiza uralensis at 1:1 ratio) in AD cell and mouse models. In Aß-GFP SH-SY5Y cells, SG-Tang reduced Aß aggregation and reactive oxygen species (ROS) production, as well as improved neurite outgrowth. When the Aß-GFP-expressing cells were stimulated with conditioned medium from interferon (IFN)-γ-activated HMC3 microglia, SG-Tang suppressed expressions of inducible nitric oxide synthase (iNOS), NLR family pyrin domain containing 1 (NLRP1) and 3 (NLRP3), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, attenuated caspase-1 activity and ROS production, and promoted neurite outgrowth. In streptozocin-induced hyperglycemic APP/PS1/Tau triple transgenic (3×Tg-AD) mice, SG-Tang also reduced expressions of NLRP1, NLRP3, Aß and Tau in hippocampus and cortex, as well as improved working and spatial memories in Y maze and Morris water maze. Collectively, our results demonstrate the potential of SG-Tang in treating AD by moderating neuroinflammation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Cognição , Medicamentos de Ervas Chinesas/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuroproteção , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Animais , Linhagem Celular , Cognição/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Proteínas de Fluorescência Verde/metabolismo , Humanos , Interferon gama/metabolismo , Memória/efeitos dos fármacos , Transtornos da Memória/complicações , Transtornos da Memória/fisiopatologia , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Modelos Biológicos , Crescimento Neuronal/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Agregados Proteicos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Aprendizagem Espacial/efeitos dos fármacos , Proteínas tau/metabolismo
8.
Molecules ; 26(9)2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34065080

RESUMO

The crude ethanol extract of the whole plant of Alternanthera philoxeroides (Mart.) Griseb was investigated for its potential as antidementia, induced by estrogen deprivation, based on in vitro antioxidant activity, ß-amyloid aggregation inhibition and cholinesterase inhibitory activity, as well as in vivo Morris water maze task (MWMT), novel object recognition task (NORT), and Y-maze task. To better understand the effect of the extract, oxidative stress-induced brain membrane damage through lipid peroxidation in the whole brain was also investigated. Additionally, expressions of neuroinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and estrogen receptor-mediated facilitation genes such as PI3K and AKT mRNA in the hippocampus and frontal cortex were also evaluated. These effects were confirmed by the determination of its serum metabolites by NMR metabolomic analysis. Both the crude extract of A. philoxeroides and its flavone constituents were found to inhibit ß-amyloid (Aß) aggregation.


Assuntos
Demência/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Metabolômica , Extratos Vegetais/farmacologia , Amaranthaceae/química , Peptídeos beta-Amiloides/química , Animais , Cognição/efeitos dos fármacos , Demência/prevenção & controle , Etanol/química , Etanol/farmacologia , Feminino , Flavonas/química , Sequestradores de Radicais Livres/metabolismo , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Medicina Tradicional do Leste Asiático , Metaboloma , Camundongos , Camundongos Endogâmicos ICR , Ovariectomia , Análise de Componente Principal , Fator de Necrose Tumoral alfa/metabolismo
9.
Nutrients ; 13(6)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063827

RESUMO

A previous systematic review revealed that lutein intake leads to improved cognitive function among older adults. However, the association between lutein intake and brain health remains unclear. METHODS: We searched the Web of Science, PubMed, PsycInfo, and Cochrane Library for research papers. The criteria were (1) an intervention study using oral lutein intake or a cross-sectional study that examined lutein levels and the brain, (2) participants were older adults, and (3) brain activities or structures were measured using a brain imaging technique (magnetic resonance imaging (MRI) or electroencephalography (EEG)). RESULTS: Seven studies using MRI (brain activities during rest, cognitive tasks, and brain structure) and two studies using EEG were included. We mainly focused on MRI studies. Three intervention studies using MRI indicated that 10 mg lutein intake over 12 months had a positive impact on healthy older adults' brain activities during learning, resting-state connectivity, and gray matter volumes. Four cross-sectional studies using MRI suggested that lutein was positively associated with brain structure and neural efficiency during cognitive tasks. CONCLUSION: Although only nine studies that used similar datasets were reviewed, this systematic review indicates that lutein has beneficial effects on healthy older adults' brain health.


Assuntos
Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Ingestão de Alimentos/psicologia , Luteína/farmacologia , Idoso , Encéfalo/diagnóstico por imagem , Envelhecimento Cognitivo/fisiologia , Estudos Transversais , Feminino , Frutas/química , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise e Desempenho de Tarefas , Verduras/química
10.
Psychopharmacology (Berl) ; 238(8): 2191-2200, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33963883

RESUMO

BACKGROUND: Zebrafish are growing in use as a model for understanding drug dependence and addiction. Sensitization paradigms have been a useful tool in identifying mechanisms involved in drug-induced behavioral and neurological changes, but in zebrafish have tended to focus on locomotor, rather than cognitive, endpoints. METHODS: Here, we used a novel method, the FMP Y-maze, which measures continuous performance through a series of repeated binary choices (L vs R), to establish a model for assessing parameters associated with psychostimulant-induced behavioral and cognitive sensitization in adult zebrafish. RESULTS: Repeat, intermittent exposure to d-amphetamine (AMPH) for 14 days increased alternations (LRLR) in the maze, suggesting improved working memory, which was enhanced further following drug challenge after a short withdrawal period, suggesting behavioral sensitization. However, this cognitive enhancement coincided with a reduction in the use of other exploration strategies, hypolocomotion, and inhibition of cognitive flexibility. Like AMPH, exposure to nicotine (NIC) increased alternations following drug challenge after chronic treatment. Repeat NIC exposure appeared to induce both cognitive and psychomotor sensitization, as evidenced by increased working memory performance (alternations) and locomotor activity, without negatively impacting other search strategies or cognitive flexibility. CONCLUSION: Chronic treatment with AMPH or NIC boosts cognitive performance in adult zebrafish. Cognitive sensitization occurred with both drugs, resulting in enhanced working memory; however, repeat AMPH exposure, following a withdrawal period, resulted in inhibited cognitive flexibility, an effect not evident with repeat NIC exposure. Cognitive and behavioral sensitization paradigms in zebrafish could serve as a useful tool for assessing cognitive states which result in cognitive enhancing or impairing effects of drugs.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Dextroanfetamina/farmacologia , Locomoção/efeitos dos fármacos , Nicotina/farmacologia , Fatores Etários , Animais , Cognição/fisiologia , Feminino , Locomoção/fisiologia , Masculino , Peixe-Zebra
11.
Nat Commun ; 12(1): 2613, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972519

RESUMO

Repeated head impact exposure can cause memory and behavioral impairments. Here, we report that exposure to non-damaging, but high frequency, head impacts can alter brain function in mice through synaptic adaptation. High frequency head impact mice develop chronic cognitive impairments in the absence of traditional brain trauma pathology, and transcriptomic profiling of mouse and human chronic traumatic encephalopathy brain reveal that synapses are strongly affected by head impact. Electrophysiological analysis shows that high frequency head impacts cause chronic modification of the AMPA/NMDA ratio in neurons that underlie the changes to cognition. To demonstrate that synaptic adaptation is caused by head impact-induced glutamate release, we pretreated mice with memantine prior to head impact. Memantine prevents the development of the key transcriptomic and electrophysiological signatures of high frequency head impact, and averts cognitive dysfunction. These data reveal synapses as a target of high frequency head impact in human and mouse brain, and that this physiological adaptation in response to head impact is sufficient to induce chronic cognitive impairment in mice.


Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Cognição , Neurônios/patologia , Sinapses/metabolismo , Sinapses/patologia , Transcriptoma/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Escala de Avaliação Comportamental , Lesões Encefálicas Traumáticas/genética , Cognição/efeitos dos fármacos , Disfunção Cognitiva/patologia , Eletrofisiologia , Ontologia Genética , Ácido Glutâmico/metabolismo , Memantina/administração & dosagem , Camundongos , Microglia/metabolismo , Família Multigênica , Plasticidade Neuronal/genética , Neurônios/citologia , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/genética , Proteínas tau/metabolismo
12.
Psychopharmacology (Berl) ; 238(8): 2297-2312, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33991198

RESUMO

RATIONALE AND OBJECTIVE: Environmental enrichment (EE) has been shown in old rats to improve learning and memory. Vitamin D (VitD) has also been shown to modulate age-related, cognitive dysfunction. As both EE and VitD could work to improve cognition via enhancement of neurotrophic factors, their effects might occlude one another. Therefore, a clinically relevant question is whether noted cognition-promoting effects of EE and VitD can co-occur. METHODS: Aged rats were housed for 6 weeks in one of three housing conditions: environmentally enriched (EE), socially enriched (SE), or standard condition (SC). Further, a 4th group was co-treated with VitD supplementation (400 IU kg-1 daily, 6 weeks) under EE conditions (EE + VitD). RESULTS: Treatment with VitD and EE housing were associated with higher score on measures of learning and memory and exhibited lower anxiety scores compared to EE alone, SE or SC as assayed in the elevated plus maze, Morris water maze, passive avoidance, and open field tasks. Additionally, in the EE + VitD group, mRNA expression levels of NGF, TrkA, BDNF, Nrf2, and IGF-1 were significantly higher compared to expression seen in the EE group. Furthermore, field potential recordings showed that EE + VitD resulted in a greater enhancement of hippocampal LTP and neuronal excitability when compared to EE alone. CONCLUSIONS: These findings demonstrate that in aged rats exposure to EE and VitD results in effects on hippocampal cognitive dysfunction and molecular mechanisms which are greater than effects of EE alone, suggesting potential for synergistic therapeutic effects for management of age-related cognitive decline.


Assuntos
Envelhecimento/fisiologia , Meio Ambiente , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Aprendizagem Espacial/fisiologia , Vitamina D/administração & dosagem , Envelhecimento/efeitos dos fármacos , Envelhecimento/psicologia , Animais , Cognição/efeitos dos fármacos , Cognição/fisiologia , Suplementos Nutricionais , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Aprendizagem Espacial/efeitos dos fármacos
13.
Cochrane Database Syst Rev ; 5: CD011922, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973646

RESUMO

BACKGROUND: Any type of seizure can be observed in Alzheimer's disease. Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with Alzheimer's disease. There are pharmacological and non-pharmacological treatments for epilepsy in people with Alzheimer's disease, however there are no current systematic reviews to evaluate the efficacy and tolerability of these treatments. This review aims to investigate these different modalities. This is an updated version of the Cochrane Review previously published in 2018. OBJECTIVES: To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with Alzheimer's disease (including sporadic Alzheimer's disease and dominantly inherited Alzheimer's disease). SEARCH METHODS: For the latest update, on 3 August 2020 we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 31 July 2020). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings; we also contacted trial authors and pharmaceutical companies. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with Alzheimer's disease, with the primary outcomes of proportion of participants with seizure freedom and proportion of participants experiencing adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to there being limited available data. MAIN RESULTS: We included one randomized controlled trial (RCT) on pharmacological interventions; the trial included 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam versus lamotrigine (RR) 1.20, 95% CI 0.53 to 2.71; 67 participants; very low-certainty evidence), levetiracetam versus phenobarbital (RR 1.01, 95% CI 0.47 to 2.19; 66 participants; very low-certainty evidence), or lamotrigine versus phenobarbital (RR 0.84, 95% CI 0.35 to 2.02; 57 participants; very low-certainty evidence). It seemed that levetiracetam could improve cognition and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood. The risk of bias relating to allocation, blinding and selective reporting was unclear. We judged the certainty of the evidence for all outcomes to be very low. AUTHORS' CONCLUSIONS: This review does not provide sufficient evidence to support levetiracetam, phenobarbital or lamotrigine for the treatment of epilepsy in people with Alzheimer's disease. Regarding efficacy and tolerability, no significant differences were found between levetiracetam, phenobarbital and lamotrigine. Large RCTs with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with Alzheimer's disease.


Assuntos
Doença de Alzheimer/complicações , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Fenobarbital/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Cognição/efeitos dos fármacos , Depressão/complicações , Depressão/tratamento farmacológico , Feminino , Humanos , Lamotrigina/administração & dosagem , Levetiracetam/administração & dosagem , Masculino , Fenobarbital/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Prevenção Secundária
15.
Acta Neurol Scand ; 144(2): 179-191, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33899218

RESUMO

OBJECTIVE: By the association of nicotinic acetylcholine receptors in the brain, nicotine in the therapeutic window lowers neuronal damage and raises protective factors. These data, however, are contradicted by other findings. Here, we assessed the effects of transdermal nicotine administration on cognitive functions in healthy non-smoker adults by systematic review and meta-analysis of clinical trials. METHODS: We included reports of clinical trials comparing the effects of nicotine patches with placebo in healthy non-smoking adults. The main outcome was the impact of nicotine patches on overall cognitive function with a focus on attention and memory. Standard meta-analytic and statistical methods measured the effect of transdermal nicotine compared with placebo patches. RESULTS: We included 31 publications involving 978 subjects. Nicotine patches boosted cognitive function in healthy adults (0.233 SMD, 95%CI, 0.111-0.355, p < .001). Overall heterogeneity of the studies was found to be modest (Ï°2  = 68.24, T2  = 0.07, I2  = 50.17%, p < .001). Also, nicotine patches improved attention (0.231 SMD, 95%CI, 0.106-0.356, p < .001). We found the inter-study heterogeneity to be low (Ï°2  = 40.95, T2  = 0.03, I2  = 34.07%, p = .042). Further, the enhancement of memory by transdermal nicotine did not reach statistical significance in normal subjects (0.270 SMD, 95% CI, -0.293-0.833, p = .347). Also, high inter-study heterogeneity was found among studies (Ï°2  = 27.25, T2  = 0.43, I2  = 77.98%, p < .001). CONCLUSION: The meta-analysis showed that transdermal nicotine had statistically significant positive effects on attention, and non-significant effects on memory, in healthy non-smoking adults. The results encourage further studies of the therapeutic potential of nicotine patches in disorders of cognition.


Assuntos
Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Nicotina/administração & dosagem , Administração Cutânea , Adulto , Humanos , Masculino , Abandono do Hábito de Fumar/métodos , Adulto Jovem
16.
Life Sci ; 278: 119526, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33894268

RESUMO

AIMS: White matter damage is the main pathological feature of chronic cerebral hypoperfusion (CCH) and glial activation is crucial in this process. Physical exercise has protective effects on CCH, but the mechanism is unclear. Therefore, this study focuses on investigating the influence of physical exercise on activated astrocytes polarization and its role in CCH. MAIN METHODS: Rats were given wheel running 48 h after 2VO (2 vessel occlusion) surgery. The cognitive function was evaluated by Morris water maze and novel object recognition test. Inflammatory cytokines expressions were detected by ELISA. Astrocytes polarization was analyzed by immunofluorescence. Myelin debris clearance and remyelination were detected by immunofluorescence and transmission electron microscopy. KEY FINDINGS: Astrocytes were activated and mainly switched to A1 phenotype in rats 2 and 3 months after 2VO. Myelin debris deposition and limited remyelination can be observed at the corresponding time. Whereas physical exercise can improve the cognitive function of 2VO rats, downregulate the expression of inflammatory factors IL-1α, C1q and TNF, upregulate the release of TGFß, and promote activated astrocytes transformation from A1 to A2 phenotype. In addition, it can also enhance myelin debris removal and remyelination. SIGNIFICANCE: These findings suggest that the benefits of physical exercise on white matter repair and cognition improvement may be related to its regulation of astrocytes polarization, which contributes to myelin debris clearance and effective remyelination in CCH.


Assuntos
Astrócitos/citologia , Astrócitos/metabolismo , Bainha de Mielina/química , Neuroglia/metabolismo , Condicionamento Físico Animal , Substância Branca/patologia , Animais , Isquemia Encefálica/patologia , Cognição/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Inflamação , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Atividade Motora , Reconhecimento Visual de Modelos , Perfusão , Fenótipo , Ratos , Ratos Wistar , Remielinização
17.
Biomed Pharmacother ; 139: 111577, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33839493

RESUMO

INTRODUCTION: Diabetes mellitus is related to cognitive impairments and molecular abnormalities of the hippocampus. A growing body of evidence suggests that Urtica dioica (Ud) and exercise training (ET) have potential therapeutic effects on diabetes and its related complications. Therefore, we hypothesized that the combined effect of exercise training (ET) and Ud might play an important role in insulin signaling pathway, oxidative stress, neuroinflammation, and cognitive impairment in diabetic rats. METHODS: Forty animals were divided into five groups (N = 8): healthy-sedentary (H-sed), diabetes-sedentary (D-sed), diabetes-exercise training (D-ET), diabetes-Urtica dioica (D-Ud), diabetes-exercise training-Urtica dioica (D-ET-Ud). Streptozotocin (STZ) (Single dosage; 45 mg/kg, i.p.) was used to induce diabetes. Then, ET (moderate intensity/5day/week) and Ud extract (50 mg/kg, oral/daily) were administered for six weeks. We also investigated the effects of ET and Ud on cognitive performance (assessed through Morris Water Maze tests), antioxidant capacity, and lipid peroxidation markers in hippocampus. Furthermore, we measured levels of insulin sensitivity and signaling factors (insulin-Ins, insulin receptor-IR and insulin-like growth factor-1 receptor-IGF-1R), and neuroinflammatory markers (IL-1 ß, TNF-α). This was followed by TUNEL assessment of the apoptosis rate in all regions of the hippocampus. RESULTS: D-sed rats compared to H-sed animals showed significant impairments (P < 0.001) in hippocampal insulin sensitivity and signaling, oxidative stress, neuroinflammation, and apoptosis, which resulted in cognitive dysfunction. Ud extract and ET treatment effectively improved these impairments in D-ET (P < 0.001), D-Ud (P < 0.05), and D-ET-Ud (P < 0.001) groups compared to D-sed rats. Moreover, diabetes mediated hippocampal oxidative stress, neuroinflammation, insulin signaling deficits, apoptosis, and cognitive dysfunction was further reversed by chronic Ud+ET administration in D-ET-Ud rats (P < 0.001) compared to D-sed animals. CONCLUSIONS: Ud extract and ET ameliorate cognitive dysfunction via improvement in hippocampal oxidative stress, neuroinflammation, insulin signaling pathway, and apoptosis in STZ-induced diabetic rats. The results of this study provide new experimental evidence for using Ud+ET in the treatment of hippocampal complications and cognitive dysfunction caused by diabetes.


Assuntos
Cognição/efeitos dos fármacos , Diabetes Mellitus Experimental/psicologia , Diabetes Mellitus Experimental/terapia , Encefalite/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Insulina/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Urtica dioica/química , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Resistência à Insulina , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Wistar , Comportamento Sedentário
18.
Mar Drugs ; 19(4)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801706

RESUMO

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRß-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-ß (Aß) deposition in an Alzheimer's disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aß and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aß plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aß load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Cognição/efeitos dos fármacos , Nootrópicos/farmacologia , Estigmasterol/análogos & derivados , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Reconhecimento Psicológico/efeitos dos fármacos , Estigmasterol/farmacologia
19.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805947

RESUMO

The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly through other mechanisms in the periphery. While molecules utilized for brain diseases are typically bestowed with a capacity to cross the blood-brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut-microbiota-brain axis is receiving increasing attention as another indirect pathway for orally administered compounds to act on the CNS. In this review, we will briefly explore these possibilities focusing on two classes of natural products: omega-3 polyunsaturated fatty acids (n-3 PUFAs) from marine sources and polyphenols from plants. The former will be used as an example of a natural product with relatively high brain bioavailability but with tightly regulated transport and metabolism, and the latter as an example of natural compounds with low brain bioavailability, yet with a growing amount of preclinical and clinical evidence of efficacy. In conclusion, it is proposed that bioavailability data should be sought early in the development of natural products to help identifying relevant mechanisms and potential impact on prevalent CNS disorders, such as Alzheimer's disease.


Assuntos
Produtos Biológicos/farmacologia , Barreira Hematoencefálica , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Disponibilidade Biológica , Produtos Biológicos/farmacocinética , Transporte Biológico , Encéfalo/metabolismo , Sistema Nervoso Central/metabolismo , Ácidos Graxos Ômega-3/farmacocinética , Ácidos Graxos Ômega-3/farmacologia , Microbioma Gastrointestinal , Humanos , Fármacos Neuroprotetores/farmacocinética , Polifenóis/farmacocinética , Polifenóis/farmacologia
20.
Nutrients ; 13(4)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808068

RESUMO

Cognitive function is a key aspect of healthy aging. Inflammation associated with normal aging, also called inflammaging is a primary risk factor for cognitive decline. A diet high in fruits and vegetable and lower in calories, particularly a Mediterranean Diet, may lower the risk of age-related cognitive decline due in part to the associated high intake of antioxidants and polyphenols. A phenolic, Palm Fruit Bioactive complex (PFBc) derived from the extraction process of palm oil from oil palm fruit (Elaeis guineensis), is reported to offset inflammation due to its high antioxidant, especially vitamin E, and polyphenol content. The benefit is thought to be achieved via the influence of antioxidants on gene expression. It is the purpose of this comprehensive review to discuss the etiology, including gene expression, of mild cognitive impairment (MCI) specific to dietary intake of antioxidants and polyphenols and to focus on the potential impact of nutritional interventions specifically PFBc has on MCI. Several in vitro, in vivo and animal studies support multiple benefits of PFBc especially for improving cognitive function via anti-inflammatory and antioxidant mechanisms. While more human studies are needed, those completed thus far support the benefit of consuming PFBc to enhance cognitive function via its anti-inflammatory antioxidant functions.


Assuntos
Envelhecimento/efeitos dos fármacos , Cognição/efeitos dos fármacos , Inflamação/tratamento farmacológico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Polifenóis/farmacologia , Envelhecimento/fisiologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Humanos , Polifenóis/química
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