Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 344
Filter
1.
Dement. neuropsychol ; 15(3): 299-313, Sept. 2021. tab, graf
Article in English | LILACS | ID: biblio-1339793

ABSTRACT

ABSTRACT Aging has been associated with the functional decline of episodic memory (EM). Unanswered questions are whether the decline of EM occurs even during healthy aging and whether this decline is related to amyloid-β (Aβ) deposition in the hippocampus. Objective: The main purpose of this study was to investigate data on the relationship between the age-related EM decline and Aβ deposition. Methods: We searched the Cochrane, MEDLINE, Scopus, and Web of Science databases and reference lists of retrieved articles that were published in the past 10 years. The initial literature search identified 517 studies. After screening the title, abstract, key words, and reference lists, 56 studies met the inclusion criteria. Results: The overall results revealed that increases in Aβ are related to lower hippocampal volume and worse performance on EM tests. The results of this systematic review revealed that high levels of Aβ may be related to EM deficits and the progression to Alzheimer's disease. Conclusions: We discussed the strengths and pitfalls of various tests and techniques used for investigating EM and Aβ deposition, methodological issues, and potential directions for future research.


RESUMO O envelhecimento tem sido associado a um declínio funcional da memória episódica (ME). Algo ainda sem resposta é se o declínio da ME ocorre mesmo no envelhecimento saudável e se esse declínio pode estar relacionado à deposição de Aβ no hipocampo. Objetivo: Nosso objetivo principal foi investigar os dados sobre a relação entre a memória episódica e a deposição de Aβ no envelhecimento saudável. Métodos: Nós buscamos nas bases de dados Cochrane, MEDLINE, Scopus, Web of Science e nas listas de referências dos estudos dos últimos 10 anos. A busca inicial nas bases de dados identificou 517 estudos. Após a triagem de título, resumos, palavras-chave e referências, 56 estudos atenderam aos critérios de inclusão. Resultados: O resultado geral revelou que o aumento de Aβ estava relacionado ao menor volume do hipocampo e pior desempenho em testes de ME. Em resumo, os resultados da presente revisão sistemática revelaram que altos níveis de Aβ podem estar relacionados ao declínio de ME e conversão progressiva para a Doença de Alzheimer. Conclusões: Aqui, discutimos os pontos fortes e as limitações dos testes e técnicas para investigar a deposição ME e Aβ, bem como questões metodológicas e direções futuras.


Subject(s)
Humans , Memory , Aging , Amyloid beta-Peptides , Memory, Episodic , Healthy Aging , Systematic Review
2.
Bol. latinoam. Caribe plantas med. aromát ; 20(4): 406-415, jul. 2021. ilus, tab
Article in English | LILACS | ID: biblio-1352429

ABSTRACT

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Sever cognitive and memory impairments, huge increase in the prevalence of the disease, and lacking definite cure have absorbed worldwide efforts to develop therapeutic approaches. Since many drugs have failed in the clinical trials due to multifactorial nature of AD, symptomatic treatments are still in the center attention and now, nootropic medicinal plants have been found as versatile ameliorators to reverse memory disorders. In this work, anti-Alzheimer's activity of aqueous extract of areca nuts (Areca catechu L.) was investigated via in vitro and in vivo studies. It depicted good amyloid ß (Aß) aggregation inhibitory activity, 82% at 100 µg/mL. In addition, it inhibited beta-secretase 1 (BACE1) with IC50 value of 19.03 µg/mL. Evaluation of neuroprotectivity of the aqueous extract of the plant against H2O2-induced cell death in PC12 neurons revealed 84.5% protection at 1 µg/mL. It should be noted that according to our results obtained from Morris Water Maze (MWM) test, the extract reversed scopolamine-induced memory deficit in rats at concentrations of 1.5 and 3 mg/kg.


La enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo relacionado con la edad. Los severos deterioros cognitivos y de la memoria, el enorme aumento de la prevalencia de la enfermedad y la falta de una cura definitiva han absorbido los esfuerzos mundiales para desarrollar enfoques terapéuticos. Dado que muchos fármacos han fallado en los ensayos clínicos debido a la naturaleza multifactorial de la EA, los tratamientos sintomáticos siguen siendo el centro de atención y ahora, las plantas medicinales nootrópicas se han encontrado como mejoradores versátiles para revertir los trastornos de la memoria. En este trabajo, se investigó la actividad anti-Alzheimer del extracto acuoso de nueces de areca (Areca catechu L.) mediante estudios in vitro e in vivo. Representaba una buena actividad inhibidora de la agregación de amiloide ß (Aß), 82% a 100 µg/mL. Además, inhibió la beta-secretasa 1 (BACE1) con un valor de CI50 de 19,03 µg/mL. La evaluación de la neuroprotección del extracto acuoso de la planta contra la muerte celular inducida por H2O2 en neuronas PC12 reveló una protección del 84,5% a 1 µg/mL. Cabe señalar que, de acuerdo con nuestros resultados obtenidos de la prueba Morris Water Maze (MWM), el extracto revirtió el déficit de memoria inducido por escopolamina en ratas a concentraciones de 1,5 y 3 mg/kg.


Subject(s)
Animals , Rats , Areca/chemistry , Plant Extracts/administration & dosage , Alzheimer Disease/drug therapy , beta-Amylase/antagonists & inhibitors , Amyloid beta-Peptides/drug effects , Aspartic Acid Endopeptidases/antagonists & inhibitors , Aspartic Acid Endopeptidases/drug effects , Neuroprotective Agents , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Amyloid Precursor Protein Secretases/drug effects , Alzheimer Disease/enzymology , Alzheimer Disease/prevention & control , Morris Water Maze Test , Medicine, Traditional
3.
Chinese Medical Journal ; (24): 646-654, 2021.
Article in English | WPRIM | ID: wpr-878078

ABSTRACT

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive; consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.


Subject(s)
Amyloid beta-Peptides , Cerebral Amyloid Angiopathy , Cerebral Hemorrhage , Humans , Inflammation , Magnetic Resonance Imaging , Vasculitis
4.
Article in Chinese | WPRIM | ID: wpr-877608

ABSTRACT

OBJECTIVE@#To screen protein target in prevention and treatment with electroacupuncture (EA) for Alzheimer's disease (AD) and explore the potential mechanism of EA in prevention of AD.@*METHODS@#A total of 40 APP/PS1 transgenic young male mice, 1.5-month old, were randomized into an EA group and a model group, 20 mice in each one, and 20 C57BL/6J mice were chosen as the normal control group. After adaptive housing for 1 week, the mice in the EA group were stimulated with EA at "Baihui" (GV 20), "Fengfu" (GV 16) and "Shenshu" (BL 23), with intermittent wave, 10 Hz in frequency and 2 mA in electric intensity. EA was given once daily, 20 min each time. There was 1 day at interval after EA for 6 days each week. Totally, the intervention lasted for 16 weeks. On day 3 after the end of EA intervention, Morris water maze test was adopted to detect learning and memory abilities of mice in each group. After water maze test, the label-free method was used to measure the difference expressions in cerebral cortex and hippocampus. Using Western blot method, the expressions of guanylate binding protein beta 5 (GNB 5) and histone-H 3 in cerebral cortex and hippocampus were verified. Using immunohistochemical method, the expressions of amyloid beta protein (Aβ) in cerebral cortex and hippocampus were detected.@*RESULTS@#Compared with the normal control group, the escape latency (on day 2, 3 and 4) was prolonged, the frequency of crossing platform and the duration of platform stay were decreased in the mice of the model group (@*CONCLUSION@#The intervention with EA effectively prevents from the decline of learning and memory ability and the formation of Aβ senile plaques in cerebral cortex and hippocampus in young mouse models of AD after growing up. Besides, EA plays a regulatory function for protein expression differences induced by AD model.


Subject(s)
Alzheimer Disease/therapy , Amyloid beta-Peptides/genetics , Animals , Disease Models, Animal , Electroacupuncture , Hippocampus , Male , Mice , Mice, Inbred C57BL , Proteomics
5.
Clinics ; 76: e2348, 2021. graf
Article in English | LILACS | ID: biblio-1153978

ABSTRACT

OBJECTIVES: TTP488, an antagonist of the receptor for advanced glycation end-products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer's disease (AD). However, the mechanism underlying the protective action of TTP488 against AD has not yet been fully explored. METHODS: Healthy male rats were exposed to aberrant amyloid β (Aβ) 1-42. Lipopolysaccharide (LPS) and the NOD-like receptor family pyrin domain containing 1 (NLRP1) overexpression lentivirus were injected to activate the NLRP1 inflammasome and exacerbate AD. TTP488 was administered to reverse AD injury. Finally, tofacitinib and fludarabine were used to inhibit the activity of Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) to prove the relationship between the JAK/STAT signaling pathway and TTP488. RESULTS: LPS and NLRP1 overexpression significantly increased the NLRP1 levels, reduced neurological function, and aggravated neuronal damage, as demonstrated by the impact latency time of, time spent by, and length of the platform covered by, the mice in the Morris water maze assay, Nissl staining, and immunofluorescence staining in rats with AD. CONCLUSIONS: TTP488 administration successfully reduced AD injury and reversed the aforementioned processes. Additionally, tofacitinib and fludarabine administration could further reverse AD injury after the TTP488 intervention. These results suggest a new potential mechanism underlying the TTP488-mediated alleviation of AD injury.


Subject(s)
Animals , Male , Mice , Rats , Janus Kinases/metabolism , Alzheimer Disease/drug therapy , Tyrosine , Transducers , Signal Transduction , Amyloid beta-Peptides , Janus Kinase 2 , Receptor for Advanced Glycation End Products , Imidazoles
6.
Article in English | WPRIM | ID: wpr-879970

ABSTRACT

Transient receptor potential M2 (TRPM2) ion channel is a non-selective cationic channel that can permeate calcium ions, and plays an important role in neuroinflammation, ischemic reperfusion brain injury, neurodegenerative disease, neuropathic pain, epilepsy and other neurological diseases. In ischemic reperfusion brain injury, TRPM2 mediates neuronal death by modulating the different subunits of glutamate N-methyl-D-aspartic acid receptor in response to calcium/zinc signal. In Alzheimer's disease, TRPM2 is activated by reactive oxygen species generated by β-amyloid peptide to form a malignant positive feedback loop that induces neuronal death and is involved in the pathological process of glial cells by promoting inflammatory response and oxidative stress. In epilepsy, the TRPM2-knockout alleviates epilepsy induced neuronal degeneration by inhibiting autophagy and apoptosis related proteins. The roles of TRPM2 channel in the pathogenesis of various central nervous system diseases and its potential drug development and clinical application prospects are summarized in this review.


Subject(s)
Amyloid beta-Peptides/metabolism , Humans , Neurodegenerative Diseases , Neuroglia , TRPM Cation Channels/genetics , Transient Receptor Potential Channels
7.
Arq. neuropsiquiatr ; 78(5): 277-281, May 2020. tab, graf
Article in English | LILACS | ID: biblio-1131706

ABSTRACT

ABSTRACT Background: Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by progressive deposition of β-amyloid peptides in the walls of small and medium-sized cortical and leptomeningeal vessels. Until today, the prevalence of CAA is unknown in our region. Objective: This study aims to analyze the prevalence of this entity in a specific elderly population in a tertiary hospital in Northeastern Brazil. Methods: A cross-sectional, retrospective study with the enrollment of patients aged 65 or older followed in the neurological outpatient service of the Universidade Federal do Piauí, Brazil, who underwent brain magnetic resonance imaging (MRI) from July 2016 to June 2018. Results: One hundred and seventy-four patients were enrolled, of whom 100 were women (57.4%) and 74, men (42.6%), aged from 65 to 91 years old (median age 73.27). Nine patients were excluded from the study due to unavailability of MRI sequences needed for an appropriate analysis. Out of the 165 remaining patients, 12 (7.2%) had established the diagnosis of CAA, according to the modified Boston criteria. Conclusion: The prevalence of CAA in our study was like those of medical literature, with a progressive age-related increase.


RESUMO Introdução: A angiopatia amiloide cerebral (AAC) é uma desordem vascular causada pela deposição progressiva de peptídeos β-amiloides nas paredes de pequenos e médios vasos corticais e leptomeníngeos. Até a presente data, a epidemiologia da AAC é desconhecida em nossa região. Objetivos: Avaliar a prevalência da AAC em uma população específica de pacientes idosos de um hospital terciário no nordeste brasileiro. Métodos: Estudo transversal, retrospectivo, com seleção de pacientes com idade igual ou superior a 65 anos, acompanhados no serviço de Neurologia do Hospital Universitário da Universidade Federal do Piauí, Brasil, e que foram submetidos a exame de ressonância nuclear magnética entre julho de 2016 e junho de 2018. Resultados: Foram recrutados 174 pacientes, dos quais 100 eram mulheres (57,4%) e 74 homens (42,6%), com idades entre 65 e 91 anos (média de 73,27). Nove pacientes foram excluídos devido à indisponibilidade de sequências de ressonância magnética necessárias para uma análise apropriada. Dos 165 pacientes restantes, 12 (7,2%) foram diagnosticados com AAC de acordo com os critérios de Boston modificados. Conclusão: A prevalência da AAC em nosso estudo foi semelhante ao resultado encontrado na literatura médica, com um aumento progressivo relacionado à idade.


Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Cerebral Amyloid Angiopathy , Brazil , Boston , Cross-Sectional Studies , Retrospective Studies , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/chemistry
8.
Int. j. morphol ; 38(1): 230-234, Feb. 2020. graf
Article in English | LILACS | ID: biblio-1056427

ABSTRACT

The hypotheses currently considered the most likely causes of Alzheimer's disease (AD) are amyloid beta peptide deposition in the cerebral cortex and hyperphosphorylation of the Tau protein, with the consequent formation of neurofibrillary tangles. In clinical practice, although not accurate, AD diagnosis is based on the exclusion of other diseases, behavioural assessments and complementary examinations, such as imaging and blood tests. Advances in the field of biotechnology have created exciting prospects for the early detection of AD via biomarker assessment, which is considered a safer and more efficient procedure. Molecules recognised as biomarkers can be expressed in some body fluids, including cerebrospinal fluid, saliva and blood. The presence of amyloid beta peptide and Tau can be confirmed in saliva, which is also an easily and non-invasively collectable material with an accessible cost. The objective was evaluate the concentrations of the t-Tau protein and Ab42 peptide in the saliva of elderly individuals with and without dementia of the AD type Method: The objective of this case-control study, involving a total of 120 individuals, was to analyse whether a correlation exists between variations in the concentrations of the t-Tau and Ab42 biomarkers in the saliva of patients with confirmed AD and individuals in the inclusion group but without AD . We found that t-Tau expression in AD patients is significantly lower than that in individuals without AD, whereas the salivary concentration of Ab42 is higher in patients with AD but not significantly different from that of the group without AD. Conclusion: Thus, we demonstrate the feasibility of using salivary biomarkers as predictive markers for diagnosis of Alzheimer's disease.


Las hipótesis consideradas actualmente como las causas más probables de la enfermedad de Alzheimer (EA) son la deposición de péptido beta amiloide en la corteza cerebral y la hiperfosforilación de la proteína Tau, con la consiguiente formación de ovillos neurofibrilares. En la práctica clínica, aunque no es precisa, el diagnóstico de la EA se basa en la exclusión de otras enfermedades, evaluaciones de comportamiento y exámenes complementarios, como imágenes y análisis de sangre. Los avances en el campo de la biotecnología han creado interesantes perspectivas para la detección temprana de la EA a través de la evaluación de biomarcadores, que se considera un procedimiento más seguro y más eficiente. Las moléculas reconocidas como biomarcadores se pueden expresar en algunos fluidos corporales, incluidos el líquido cerebroespinal, la saliva y la sangre. La presencia del péptido beta amiloide (AB) y la proteína Tau (t-Tau) se puede confirmar en la saliva, que también es un material fácil y no invasivo de recolección con un costo accesible. El objetivo fue evaluar las concentraciones de la proteína t-Tau y el péptido Ab42 en la saliva de las personas de edad avanzada con y sin demencia del tipo de tipo EA. El estudio de casos y controles, se realizó en un total de 120 personas, para analizar si existe una correlación entre las variaciones en las concentraciones de los biomarcadores t-Tau y Ab42 en la saliva de pacientes con EA confirmada e individuos en el grupo de inclusión pero sin AD. Encontramos que la expresión de t-Tau en pacientes con EA es significativamente menor que en individuos sin EA, mientras que la concentración salival de Ab42 es mayor en pacientes con EA pero no significativamente diferente de la del grupo sin la enfermedad . Por lo tanto, se demuestra la viabilidad del uso de biomarcadores salivales como marcadores predictivos para el diagnóstico de la enfermedad de Alzheimer.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Amyloid beta-Peptides/metabolism , tau Proteins/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Saliva/metabolism , Saliva/chemistry , Biomarkers/analysis , Biomarkers/metabolism , Amyloid beta-Peptides/analysis , tau Proteins/analysis
9.
Article in Chinese | WPRIM | ID: wpr-878825

ABSTRACT

Alzheimer's disease(AD) is a neurodegenerative disease that has no effective drug to cure it. Studies in several AD models have shown that Erigeron breviscapus and its active ingredients(scutellarin and caffeoylquinic acid) could improve/enhance the learning and memory ability, and the mechanisms are associated with inhibiting amyloid β(Aβ) production, aggregation, fibrosis and Aβ neurotoxicity toxicity, regulating cholinergic nervous system, inhibiting oxidative stress and inflammation, inhibiting tau hyperphosphorylation, improving mitochondrial function, and resisting neuronal apoptosis. This article systematically reviewed the research progress of E. breviscapus and its active ingredients for treatment of AD in AD models, in the expectation of providing references for further development of E. breviscapus's medicinal potential.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Erigeron , Humans , Neurodegenerative Diseases
10.
Chinese Medical Journal ; (24): 173-177, 2020.
Article in English | WPRIM | ID: wpr-878026

ABSTRACT

BACKGROUND@#Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population.@*METHODS@#We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed.@*RESULTS@#In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0-8.0] vs. 8.0 [4.5-10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher β-Amyloid (1-42) (Aβ42) levels and lower phospho-tau/Aβ42 and total tau/Aβ42 ratios in the CSF of non-AD subjects (P < 0.05).@*CONCLUSION@#Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Case-Control Studies , Cognition , Cross-Sectional Studies , Humans , Peptide Fragments , tau Proteins
12.
Article in Chinese | WPRIM | ID: wpr-828922

ABSTRACT

OBJECTIVE@#To investigate the effects of stachydrine (STA) on apoptosis of Aβ-induced PC12 cells mimicking Alzheimer's disease and explore the mechanisms.@*METHODS@#The differential genes of STA were analyzed based on GSE85871 data, and the target genes of STA were identified using STITCH database. PC12 cells were treated with Aβ to establish a cell model of Alzheimer's disease, and the changes in cell viability and cell cycle in response to STA treatment were assessed using MTT assay and flow cytometry, respectively. RT-PCR and Western blotting were used to detect the relevant gene or protein expressions in the treated cells.@*RESULTS@#GSE85871 data showed 37 up-regulated genes and 48 down-regulated genes in cells following treatment with STA. Analysis of the data from the STITCH database indicated that RPS8 and EED were the target genes of STA. Treatment of PC12 cells with Aβ significantly lowered the cell viability ( < 0.05) and the expressions of RPS8 and EED at both the mRNA and protein levels ( < 0.05), and obviously inhibited the expression of apoptosis-related proteins Bcl-2 and p53 ( < 0.05). STA treatment of the cells significantly reversed the effect of Aβ and induced cell cycle arrest in G2/M phase, causing also significantly increases in the expression levels of RPS8, EED, Bcl-2 and p53 ( < 0.05).@*CONCLUSIONS@#STA plays an important role in inhibiting the apoptosis of PC12 cells induced by Aβ possibly by regulating RPS8 and EED expression to promote the expressions of Bcl-2 and p53.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Animals , Apoptosis , Cell Survival , PC12 Cells , Peptide Fragments , Rats
13.
Article in Chinese | WPRIM | ID: wpr-828066

ABSTRACT

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aβ_(25-35) oligomers(final concentration 40 μmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aβ_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aβ-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 μmol·L~(-1) Aβ_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aβ_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aβ_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aβ_(25-35) transport across the blood-brain barrier.


Subject(s)
Amyloid beta-Peptides , Animals , Blood-Brain Barrier , Drugs, Chinese Herbal , Endothelial Cells , Humans
14.
Article in Chinese | WPRIM | ID: wpr-827966

ABSTRACT

Huangpu Tongqiao Capsules(HPTQC), with the functions of invigorating Qi and kidney, eliminating phlegm and removing blood stasis, have the effect of treating Alzheimer's disease(AD), but its mechanism needs further exploration. To explore the relationship between the therapeutic mechanism of HPTQC on Alzheimer's disease and EGFR-PLCγ signal pathway, 40 healthy male SD rats were selected and divided into 4 groups randomly: sham operation group(sham), model group(model), HPTQC group(HPTQC), and nimodipine group(NMP). AD rat model was established by intraperitoneal injection of D-galactose combined with an intracerebral injection of amyloid-β peptide(25-35). After 28 days of administration, Morris water maze test and HE staining showed that the learning and memory ability of AD rats were significantly decreased(P<0.01), and hippocampal neurons were obviously da-maged. However, HPTQC could improve the learning and memory ability of AD rats(P<0.05) and reduce the damage of hippocampal neurons. Immunofluorescence test results showed that the expression levels of EGFR and p-Tau in hippocampal CA1 region of AD rats were significantly increased(P<0.01), and HPTQC could reduce the expression of EGFR and p-Tau in hippocampus of AD rats(P<0.01). Western blot results showed that the protein expression levels of EGFR, PLCγ, IP3 R and p-Tau in hippocampus of AD rats were significantly increased(P<0.01), and HPTQC could reduce the protein expression of EGFR, PLCγ, IP3 R and p-Tau in AD rats(P<0.05). RT-PCR results showed that the mRNA levels of EGFR, PLCγ, IP3 R and Tau in hippocampus of AD rats were significantly increased(P<0.01), and HPTQC could reduce the mRNA levels of EGFR, PLCγ, IP3 R and Tau in AD rats(P<0.05). The results indicate that HPTQC can improve the learning and memory ability of AD rats, and its mechanism of action may be related to regulating EGFR-PLCγ signal pathway.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Animals , Capsules , Disease Models, Animal , ErbB Receptors , Hippocampus , Male , Rats , Rats, Sprague-Dawley , Signal Transduction
15.
Article in Chinese | WPRIM | ID: wpr-826727

ABSTRACT

OBJECTIVE@#To compare the therapeutic effect of electroacupuncture (EA) combined with donepezil hydrochloride and donepezil hydrochloride alone on improving learning-memory ability in patients with Alzheimer's disease (AD), and to explore its action mechanism.@*METHODS@#Sixty patients of AD were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the observation group were treated with EA at governor vessel (GV) combined with donepezil hydrochloride. EA was applied at Baihui (GV 20) and Fengfu (GV 16) with dilatational wave (10 Hz/50 Hz of frequency, 0.5 to 5.0 mA of intensity), and the needles were kept for 40 min, EA was given once a day; the donepezil hydrochloride tablet was taken orally, 5 mg, once a day, and after 4 weeks the dosage might be increased to 10 mg per day according to the specific situation. All the treatment was given for 8 weeks. The patients in the control group were only treated with donepezil hydrochloride with the identical procedure as the observation group. The Montreal cognitive assessment (MoCA) and Alzheimer's disease assessment scale cognitive part (ADAS-Cog) were evaluated before and after treatment; P300 (latency and amplitude of N2 and P3) was detected by EEG/ERP system brain event related potential instrument, and amyloid precursor protein (APP) and β-amyloid protein 1-42 (Aβ) were detected by ELISA.@*RESULTS@#Compared before treatment, the MoCA scores were increased after treatment in the two groups (<0.05), and the MoCA score in the observation group was higher than that in the control group (<0.05). Compared before treatment, the ADAS-Cog scores were decreased after treatment in the two groups (<0.05), and the ADAS-Cog score in the observation group was lower than that in the control group (<0.05). Compared before treatment, the latency of N2 and P3 was shortened and the amplitude was increased after treatment in the two groups (<0.05); after treatment, the latency of N2 and P3 in the observation group was shorter than that in the control group and the amplitude was higher than that in the control group (<0.05). Compared before treatment, the serum levels of APP and Aβ were lower after treatment in the two groups (<0.05), and the serum levels of APP and Aβ in the observation group were lower than those in the control group (<0.05).@*CONCLUSION@#EA at Baihui (GV 20) and Fengfu (GV 6) combined with donepezil hydrochloride can effectively reduce the serum levels of APP and Aβ and improve the scores of MoCA and ADAS-Cog and the levels of N2 and P3 of P300 in AD patients, which has superior effect to donepezil hydrochloride alone in improving the learning-memory of AD patients.


Subject(s)
Alzheimer Disease , Blood , Therapeutics , Amyloid beta-Peptides , Blood , Amyloid beta-Protein Precursor , Blood , Cognition , Donepezil , Therapeutic Uses , Electroacupuncture , Humans , Learning , Memory , Peptide Fragments , Blood
16.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(6): 479-484, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055343

ABSTRACT

Objective: The relationship between biomarkers of amyloid-beta aggregation (Aβ1-42) and/or neurodegeneration (Tau protein) in cerebrospinal fluid (CSF) and cognitive decline is still unclear. We aimed to ascertain whether CSF biomarkers correlate with cognitive performance in healthy and cognitively impaired subjects, starting from clinical diagnoses. Methods: We tested for correlation between CSF biomarkers and Mini-Mental State Examination (MMSE) scores in 208 subjects: 54 healthy controls, 82 with mild cognitive impairment (MCI), 46 with Alzheimer's disease (AD), and 26 with other dementias (OD). Results: MMSE correlated weakly with all CSF biomarkers in the overall sample (r = 0.242, p < 0.0006). Aβ1-42 and MMSE correlated weakly in MCI (r = 0.247, p = 0.030), and moderately in OD (r = 0.440, p = 0.027). t-Tau showed a weak inverse correlation with MMSE in controls (r = -0.284, p = 0.043) and MCI (r = -0.241, p = 0.036), and a moderate/strong correlation in OD (r = 0.665), p = 0.0003). p-Tau correlated weakly with MMSE in AD (r = -0.343, p = 0.026) and moderately in OD (r = -0.540, p = 0.0005). The Aβ1-42/p-Tau ratio had a moderate/strong correlation with MMSE in OD (r = 0.597, p = 0.001). Conclusion: CSF biomarkers correlated best with cognitive performance in OD. t-Tau correlated weakly with cognition in controls and patients with MCI. In AD, only p-Tau levels correlated with cognitive performance. This pattern, which has been reported previously, seems to indicate that CSF biomarkers might not be reliable as indicators of disease severity.


Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Peptide Fragments/cerebrospinal fluid , Amyloid beta-Peptides/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , Alzheimer Disease/cerebrospinal fluid , Cognitive Dysfunction/cerebrospinal fluid , Reference Values , Biomarkers/cerebrospinal fluid , Case-Control Studies , Analysis of Variance , Cohort Studies , Statistics, Nonparametric , Alzheimer Disease/psychology , Mental Status and Dementia Tests , Middle Aged
18.
Electron. j. biotechnol ; 40: 1-9, July. 2019. tab, graf, ilus
Article in English | LILACS | ID: biblio-1053195

ABSTRACT

BACKGROUND: Microalgae are aquatic chlorophyll-containing organisms comprising unicellular microscopic forms, and their biomasses are potential sources of bioactive compounds, biofuels and food-based products. However, the neuroprotective effects of microalgal biomass have not been fully explored. In this study, biomass from two Chlorella species was characterized, and their antioxidant, anticholinesterase and anti-amyloidogenic activities were investigated. RESULTS: GC­MS analysis of the extracts revealed the presence of some phenols, sterols, steroids, fatty acids and terpenes. Ethanol extract of Chlorella sorokiniana (14.21 mg GAE/g) and dichloromethane extract of Chlorella minutissima (20.65 mg QE/g) had the highest total phenol and flavonoid contents, respectively. All the extracts scavenged 2,2-diphenyl-1-picrylhydrazyl, 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonate) and hydroxyl radicals. The highest metal chelating activity of the extracts was observed in the ethanol extracts of C. minutissima (102.60 µg/mL) and C. sorokiniana (107.84 µg/mL). Furthermore, the cholinesterase inhibitory activities of the extracts showed that ethanol extract of C. sorokiniana (13.34 µg/mL) exhibited the highest acetylcholinesterase inhibitory activity, while dichloromethane extract of C. minutissima (11.78 µg/mL) showed the highest butyrylcholinesterase inhibitory activity. Incubation of the ß-amyloid protein increased the aggregation of amyloid fibrils after 96 h. However, ethanol extract of C. sorokiniana and C. minutissima inhibited further aggregation of Aß1­42 and caused disaggregation of matured protein fibrils compared to the control. This study reveals the modulatory effects of C. sorokiniana and C. minutissima extracts on some mediators of Alzheimer's disease and provides insights into their potential benefits as functional food, nutraceutics or therapeutic agent for the management of this neurodegenerative disease.


Subject(s)
Chlorella/chemistry , Cholinesterase Inhibitors/pharmacology , Amyloid beta-Peptides/antagonists & inhibitors , Antioxidants/pharmacology , Phenols/analysis , Steroids/analysis , Sterols/analysis , Terpenes/analysis , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cholinesterase Inhibitors/chemistry , Spectroscopy, Fourier Transform Infrared , Neuroprotective Agents , Biomass , Ethanol , Fatty Acids/analysis , Microalgae , Alzheimer Disease/prevention & control , Amyloid/drug effects , Gas Chromatography-Mass Spectrometry , Antioxidants/chemistry
19.
Article in Chinese | WPRIM | ID: wpr-781849

ABSTRACT

Alzheimer's disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-β oligomers (AβOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AβOs as an AD model to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AβOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model .


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Humans , Neurofibrillary Tangles , tau Proteins
20.
Chinese Acupuncture & Moxibustion ; (12): 1313-1318, 2019.
Article in Chinese | WPRIM | ID: wpr-781789

ABSTRACT

OBJECTIVE@#To observe the eliminating effects of moxibustion at "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14) on amyloid β-peptide (Aβ) in brain of the amyloid precursor protein/presenili1 (APP/PS1) double-transgenic mice with Alzheimer's disease (AD) by regulating the phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway.@*METHODS@#A total of 60 APP/PS1 double-transgenic mice with AD were randomly divided into a model group, a moxibustion group, a rapamycin group and a combination group (treated with moxibustion and inhibitor), 15 mice in each group, another 15 male C57BL/6J mice with same age and background were selected as the control group. In the moxibustion group, pressing moxibustion was applied at "Baihui" (GV 20) while the mild moxibustion was applied at "Fengfu" (GV 16) and "Dazhui" (GV 14). The treatment was manipulated for 20 min each time, once a day for 2 weeks. In the rapamycin group, rapamycin (2 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. On the basis of the treatment in the moxibustion group, 3-methyladenine (1.5 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. The mice in the control and the model group received normal diet and no intervention was given for 2 weeks. Immunohistochemica method was used to measure the levels of Aβ in the cerebral cortex and hippocampal, transmission electron microscopy was used to observe the formation of autophagosome in hippocampus, and Western blot method was used to observe the levels of PI3K, Akt, p-Akt, mTOR and p-mTOR in hippocampus.@*RESULTS@#Compared with the control group, the levels of Aβ in the cerebral cortex and hippocampal were increased in the model group (0.05). Compared with the rapamycin group, the levels of Aβ in the cerebral cortex and hippocampal were increased in the combination group (<0.01). In the model group, the cytoplasmic utophagic vacuoles and organelles of neuron were reduced. In the moxibustion group, the utophagic vacuoles were increased, and the organelles showed deformation and atrophy. In the rapamycin group, the utophagic vacuoles were widely disturbed and few deformed organelles were found. In the combination group, few utophagic vacuoles were found and additional organelles showed deformation and atrophy. Compared with the control group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the model group (all <0.01). Compared with the model group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were reduced in the moxibustion group, the rapamycin group and the combination group (all <0.01). Compared with the moxibustion group, the levels of PI3K、Akt、and p-mTOR were increased in the rapamycin group and the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (all <0.01). Compared with the rapamycin group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (<0.01).@*CONCLUSION@#Moxibustion at acupoints of governor vessel can enhance the autophagy process on Aβ in brain of the APP/PS1 double-transgenic AD mice, which may be associated with its effects on inhibiting the abnormal activation of PI3K/Akt/mTOR signaling pathway.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Animals , Autophagy , Disease Models, Animal , Hippocampus , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Moxibustion , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases
SELECTION OF CITATIONS
SEARCH DETAIL