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Objective:To study the clinical effects of QingxinWendan decoction in the treatment of bipolar disorder (BD) manic episode.Methods:60 patients with BD manic episode treated in Hunan Brain Hospital from February 2020 to December 2020 were prospectively selected. They were included in the control group and the observation group according to the random alphabet method, with 30 cases in each group. The control group was treated with magnesium valproate sustained-release tablets, and the observation group was treated with Qingxin Wendan decoction combined with magnesium valproate sustained-release tablets. The curative effect was evaluated after 4 weeks of continuous treatment. The degree of mania before and after treatment was evaluated by Beck-Rafaelsen mania scale (BRMS); the cognitive function before and after treatment was evaluated by Wechsler Adult Intelligence Scale (WAIS-RC) and Wechsler Memory Scale (WMS); The levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), neuron specific enolase (NSE) and amyloid β protein (Aβ) levels were measured by enzyme linked immunosorbent assay (ELISA) before and after treatment. Spearman correlation analysis was used to analyze the correlation between serum NSE and Aβ levels and WAIS-RC and WMS scores in the two groups.Results:The curative effect of the observation group was better than that of the control group, with statistically significant difference ( P<0.05). After treatment, the BRMS scores of the control group and the observation group decreased (all P<0.05), and the BRMS scores of the observation group were lower than those of the control group ( P<0.05); After treatment, the WAIS-RC and WMS scores of the control group and the observation group increased (all P<0.05), and the WAIS-RC and WMS scores of the observation group were higher than those of the control group (all P<0.05). After treatment, the serum levels of IL-1β, TNF-α, NSE and Aβ in two groups were decreased (all P<0.05), and the levels of IL-1β, TNF-α, NSE and Aβ in the observation group were lower than those in the control group (all P<0.05). NSE and Aβ levels were negatively correlated with WAIS-RC and WMS scores (all P<0.05). Conclusions:Magnesium valproate sustained-release tablets combined with Qingxin Wendan decoction in the treatment of patients with BD manic episode were superior to magnesium valproate sustained-release tablets alone in reducing manic score, IL-1β, TNF-α, NSE and Aβ levels, and improving the cognitive function of patients. The use of QingxinWendan decoction on top of valproate extended-release tablet treatment for BD manic episode was superior to treatment with valproate extended-release tablets alone in reducing mania scores, IL-1β, TNF-α, NSE and Aβ levels, as well as improving patients' cognitive function.
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RESUMO Objetivo O artigo tem como objetivo determinar as famílias de receptores mais estudadas, envolvidas com a doença de Alzheimer, assim como determinar a região do sistema nervoso na qual mais tipos de receptores são expressos e quais funções dos receptores estão predominantemente associadas com a patologia em questão. O artigo busca mostrar os modelos e métodos mais utilizados nessas pesquisas, resumindo alguns achados e discutindo o impacto desses estudos no conhecimento científico. Métodos Esta revisão utilizou-se de uma metodologia sistemática (Prospero; ID 141957). Resultados Pode-se constatar que os receptores de transcrição nuclear foram os mais estudados. A maior parte desses receptores se expressa no córtex cerebral e hipocampo. Adicionalmente, a maioria das pesquisas avaliou os receptores relacionados com os efeitos benéficos na doença. A eliminação da proteína amiloide ou o bloqueio de vias relacionadas à síntese dessa proteína foram as principais funções desempenhadas por esses receptores. Por fim, as técnicas de imunoistoquímica e reação em cadeia de polimerase em tempo real (RT-PCR), respectivamente, foram as mais utilizadas, e os roedores consistiram no principal modelo de estudo. Conclusões Os receptores de transcrição nuclear, o córtex cerebral, o hipocampo, a micróglia e a proteína beta-amiloide mostraram importância na patogênese da doença de Alzheimer neste estudo.
ABSTRACT Objective The article aims to find the receptors family involved with Alzheimer's disease most studied as well as the tissue that most receptors are expressed. This study also aims to determine the functions predominantly associated with the pathology. In addition, the work seeks to show the models and techniques most used, as well as summarize the findings and discuss the impact of these studies on scientific knowledge. Methods This review addressed a systematic methodology (Prospero; ID 141957). Results It can be seen that nuclear transcription receptors were the most studied. Most of these receptors are expressed in the cerebral cortex and hippocampus. Additionally, a great number of studies evaluated the receptors related to beneficial effects in the disease. The depletion of amyloid protein or the blockade of pathways related to its synthesis were the main functions performed by these receptors. Finally, immunohistochemistry and RT-PCR techniques, respectively, were the most used and the rodents were the main study model. Conclusions Nuclear transcription receptors, cerebral cortex and hippocampus, microglia, and amyloid beta protein have shown significant importance in the pathogenesis of Alzheimer's disease in this study.
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Objective:To study the effect of Liuwei Dihuangwan on the improvement of autophagy level of hippocampal neurons in mice with kidney deficiency Alzheimer' s disease (AD) and its partial mechanism, in order to explore part of therapeutic mechanisms of kidney-tonifying and essence-filling therapy for AD. Method:Healthy male C57-B6 mice were divided into control group, AD group, kidney deficiency AD group and Liuwei Dihuangwan group(1.08 g·kg-1). The control group and the AD group were subcutaneously injected with normal saline (15 mL·kg-1) daily, and the kidney deficiency AD group and the Liuwei Dihuangwan group were subcutaneously injected with hydrocortisone injection (15 mL·kg-1) daily for 20 consecutive days. On the 21st day, the other three groups were injected with 6 μg amyloid beta protein 25-35(Aβ25-35) in the lateral ventricle, while the control group was injected with sterile saline into the lateral ventricle. The levels of serum cortisol and testosterone in each group were detected by enzyme-linked immunosorbent assay (ELISA), the morphological changes in hippocampal neurons were observed by transmission electron microscopy, the expression of microtubule-associated protein 1 light chain 3 (LC3) was detected by immunofluorescence, and the expression of selective autophagic junction protein (p62) was detected by Western blot. Result:Compared with normal group, serum cortisol and testosterone levels in AD group and kidney deficiency AD group were significantly reduced (PPPPPPPPPConclusion:Kidney-tonifying and essence-filling therapy can protect hippocampal neurons, increase LC3 expression in hippocampal neurons, decrease p62 expression level and increase autophagy level of hippocampal neurons. It has a certain therapeutic effect on kidney-deficiency Alzheimer' s disease.
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Objective To investigate the pathways by which hypoxia aggravates the neurotoxic effects of amyloid-beta protein (Aβ) on neurons.Methods Human neuroblastoma cells (SH-SY5Y cells) were cultured in vitro,and were divided into four groups:the control group,Aβ intervention group,hypoxia group,Aβ intervention plus hypoxia group.Quantitative real time polymerase chain reaction(qRT-PCR) was adopted to detect the mRNA expression levels of p21-activated kinase 1 (PAK1),LIM kinase 1 protein (LIMK1)and cofilin.Western blot was used to measure the protein levels of PAK1,LIMK1,phosphate-LIMK1 (P-LIMK1),cofilin and phosphate-cofilin (P-cofilin).Results After Aβ treatment,the activity of SH-SY5Y cells was decreased.Compared with the control group,the protein levels of PAK1,LIMK1,P-LIMK1,P-cofilin,and the mRNA expression levels of PAK1 and LIMK1 were decreased(all P＜0.05),but the protein and mRNA expression of cofilin had no significant changes after 24 h of treatment with 10μmol/L Aβ.Compared with the Aβ intervention group,the protein levels of PAK 1,LIMK1,P-LIMK 1 and P-cofilin were decreased (all P ＜ 0.05),and the mRNA expression levels of PAK1 and LIMK1 were decreased(both P＜0.05),but the protein and mRNA expression of cofilin had no significant changes after 24 h of treatment of SH-SY5Y cells with 10 μmol/L Aβ plus 2％ oxygen.Conclusions Aβ may reduce P-LIMK1 expression by inhibiting the activity of PAK1,thereby reducing the P-cofilin,increasing the formation of dephosphorylated cofilin,leading to neural cells damage,and hypoxia aggravates the neurotoxicity of Aβ through this pathway.
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Objective To study the relationship between plasma neurodegenerative protein level and non-motor symptoms(NMS)in PD patients.Methods Eighty-four PD patients served as a PD group and 54age-matched persons undergoing physical examination served as a control group. The NMS of PD patients were assessed according to the HAMD scale.The plasma levels of tau,p-tau181,Aβ-42andα-syn were measured by ELISA and analyzed by Spearman correlation analysis and binary logistic regression analysis respectively.Results The FSS score and plasmaα-syn level were significantly higher while the plasma Aβ-42level was significantly lower in PD group than in control group(3.22±1.68 vs 1.89±1.16,P=0.000;320.00±64.91ng/L vs 277.78±52.75ng/L,P=0.000;267.61±77.75ng/L vs 321.80±49.41ng/L,P=0.001).No significant difference was detected in plasma tau and p-tau181levels between the two groups(P＞0.05).The plasmaα-syn level was positively related with the FSS score(r=0.237,P=0.030)and was an influencing factor of FSS(OR=1.019,95％CI:1.006-1.032,P=0.004).Conclusion Plasma neurodegenerative protein level is related with NMS and plasmaα-syn level is a peripheral biomarker for fatigue in PD patients.
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Objective To study the pathological features of argyrophilic grains in normal aging brain, AD, PD and progressive superior nuclear paralysis patients. Methods Brain tissue samples taken from 5 AD, 3 PD, 2 progressive superior nuclear paralysis patients with complete clinico-pathological data and 4 normal aging brain subjects were stained with HE, Luxol fast blue and Gallyas-Braak silver respectively. Aβ, tau, α-synuclein and P62 antibodies were detected by microscopy with immunohistochemical staining. The pathological features of argyrophilic grains were recorded. Results The Gallyas-Braak silver staining showed argyrophilic grain structure in 4 out of the 14 amygdaloid nucleus tissue samples (2 from AD patients, 1 from progressive superior nuclear paralysis patients and 1 from normal aging brain patients) with a positive rate of 28.6％. The immunohistochemical staining showed positive tau and P62 antibodies. Conclusion Argyrophilic grain lesion is not uncommon in aging-related neurodegenerative diseases such as normal aging brain, AD and progressive superior nuclear paralysis and can thus produce its superposition effect on the clinical symptoms of cognitive impairment in AD and progressive superior nuclear paralysis patients.
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Objective To investigate the effect and mechanisms of β hydroxybutyrate (βOHB) regulation on p75NTR expression in Alzheimer's disease (AD) model cells.Methods First,cultured SH-SY5Y cells were exposed to Aβ (final concentrations:10,20,40,80 μmol/L) with or without 5 mmol/L βOHB pretreatment,and sham-treated cells were used as the control.At 24 h after treatment,the viability of cells was determined by the MTT assay.Secondly,cultured cells were divided into four groups.Cells in the Aβ group were exposed to Aβ (final concentration:20 μ mol/L)with or without 5 mmol/L βOHB pretreatment.Cells in the βOHB group were treated only with 5 mmol/L βOHB,and sham treated cells were used as the control.At 6 h and 24 h after treatment,the expression of p75NTR,HDAC1/2 mRNA and its protein expression,and p65 protein expression were measured by qRT-PCR or Western blot.Finally,the expression of p75NTR mRNA and protein was analyzed in cultured cells after silencing HDAC1 / 2 with siRNA.Results The viability of cells with 40 μmol/L or 80 μmol/L treatment was lower than that in the control group (P＜0.01),and there was a significant increase (P＜0.01) in cell viability of the βOHB intervention group,compared with the Aβ group.At 6 h or 24 h after treatment,the expression of p75NTR mRNA,its protein expression,and p65 protein expression were clearly increased in the βOHB group (P＜0.05) and markedly decreased (P＜0.01) in the Aβ group,compared with the control.Additionally,the expression of HDAC1 / 2 mRNA and protein was higher (P＜0.01) in the Aβ group at 6h or 24h after treatment and lower(P＜0.05 or P＜0.01)in the βOHB group at 6 h after treatment than in the control group.Compared with the Aβ group,there were significant increases (P＜0.01) observed in p75NTR mRNA,its protein expression,and p65 protein expression,and a notable decrease (P＜0.05) in HDAC1 / 2 mRNA and protein expression in cells of the βOHB intervention group at 6 h and 24 h after treatment.The expression of p75NTR mRNA and protein increased in HDAC1 knock-down cells compared with the control (P＜0.05).However,no difference was found in p75NTR expression in HDAC2 knock-down cells (P＞0.05).Conclusions βOHB up-regulates p75NTR expression by inhibiting HDAC1 of βOHB.It also activates p65 and prevents the decrease of cell viability.
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Objective To study the effect of soluble amyloid precursor protein α (sAPPα) on nerve cell apoptosis and neurological function in subarachnoid hemorrhage (SAH) rats.Methods Sixty male SD rats were randomly divided into control group (n=20),SAH+saline group (n=20) and SAH+sAPPα group (n=20).A SAH model was established by injecting autologous blood into cistern magna in rats.After a SAH model was established for SAH + saline group and SAH + sAPPα group by injecting saline and sAPPα respectively into the cistern magna of rats,the apoptotic cells were detected by immunofluorescene with TUNEL staining and the neurological function was scored in 10 rats from each group on day 3 after injection of sAPPα and saline.Results The number of apoptotic cells in brain tissue was significantly greater in SAH+saline group than in control group (P＜0.05) and was significantly smaller in SAH+sAPPα group than in SAH+ saline group (P＜0.05).The neurological function score was 26.7±0.5,13.9±0.7 and 23.0±0.8 respectively in control group,SAH + saline group and SAH + sAPPα group.Conclusion sAPPα alleviates secondary damage of neurological function by inhibiting the apoptosis of nerve cells in rats after SAH and can thus improve their neurological function.
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Objective To investigate the intervention effect of CD147 on learning and memory ability in rat model of Alzheimer's disease. Methods A total of 60 healthy Sprague-Dawley rats were randomly divided into sham operation group, model group and CD147 group, 20 rats in each group. All of the rats were anesthetized with intraperitoneal injection of 10％chloral hydrate (0.3 g/kg). The rats in the model group and the CD147 group were injected with Aβ1-40 (10μg) in the bilateral hippocampal CA1 regions, while the rats in the sham operation group were injected with the same amount of saline at the same sites. After 48 h, the rats in CD147 group were injected with CD147 cDNA in the bilateral ventricles, while the rats in model group and sham operation group were injected the same amount of saline at the same sites. Morris water maze test was used to detect the ability of learning and memory of rats. The expressions ofβamyloid protein (Aβ) andγ-secretase were detected by Western blot assay. Results The escape latency was significantly longer in model group than that of sham operation group, while which was significantly lower in CD147 group than that of model group (P<0.05). The number of times across the platform and the time of staying on platform were significantly lower in model group than those of sham operation group, while which was significantly higher in the CD147 group than that of model group (P<0.05). The expressions of Aβandγ-secretase were increased significantly in model group compared to those of sham operation group, while which were significantly decreased in CD147 group compared with those of model group (P<0.05). Conclusion Exogenous CD147 can significantly improve the learning and memory ability of AD rats, and its specific mechanism may be related to regulating the activity ofγ-secretase and down regulating the expression of Aβ.
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Objective To investigate the plasma protein concentration of S100B protein,hyperphosphorylated tau protein (P-tau) and β-amyloid (Aβ1-42) of rheumatoid arthritis (RA) patients with mild cognitive impairment (MCI) and to provide a reference for clinical diagnosis and prevention of cognitive dysfunction of RA patients.Methods The subjects were consisted of three groups:RA patients with MCI,RA patients with normal cognitive function (NC) and healthy controls.The Montreal Cognitive Assessment (MoCA)was used to test patients' cognitive function,generalized anxiety disorder scale-7 (GAD-7) scale and 9-item patient health questionnaire-9 (PHQ-9) were used to exclude anxiety and depression of RA patients.The concentration of S100B protein,P-tau protein and Aβ1-42 protein in plasma was detected by enzyme-linked immunosorbent assay (ELISA),and the correlation among the concentration of S100B protein,P-tau protein and MoCA scores was analyzed by Pearson's chi-squared test.Results ① Cognitive scores showed that some RA patients had MCI.② The plasma levels of S100B (F=11.81,P＜0.05),P-tau (F=3.3,P＜0.05) protein in RA patients with MCI were higher than that in NC RA patients and the control group (P＜0.05).③ The clinical index analysis showed that the concentration of C reactive protein (CRP) in RA patients with MCI was higher than that in NC RA patients and healthy control,the difference was statistically significant (t=6.44,P＜0.05).④The levels of plasma P-tau (r=-0.539,P＜0.05),S100B (r=-0.346,P＜0.05),CRP (r=-0.358,P＜0.05) protein were negatively correlated with cognitive scores (P＜0.05).Conclusion CRP,S100B protein and P-tau protein are associated with the pathogenesis of RA patients with MCI.The consequences of plasma concentration test can be com-bined with cognitive assessment questionnaire to provide reference for clinical diagnosis of RA patients with MCI.
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Objective To investigate the effect of parecoxib sodium combined with dexmedetomi-dine on postoperative levels of plasma excitatory aminoacid and beta-amyloid protein(β-AP)in jugular bulb venous of elderly patients. Methods A total of 135 patients of either sex, aged 65-79 yr, weighing 47-76 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective open reduc-tion and internal fixation after tibial fracture and hip replacement, were divided into 3 groups(n=45 each) using a random number table: parecoxib sodium group(group P), dexmedetomidine group(group D)and parecoxib sodium combined with dexmedetomidine group(group PD). In group P, parecoxib sodium 40 mg (diluted to 5 ml in normal saline)was injected intravenously at 15 min before induction of anesthesia. In group D, dexmedetomidine was intravenously infused at a loading dose of 05 μg∕kg over 15 min starting from 15 min before induction of anesthesia, followed by an infusion of 05 μg·kg-1·h-1until the end of surgery. In group PD, parecoxib sodium 40 mg(diluted to 5 ml in normal saline)was intravenously injec-ted at 15 min before induction of anesthesia, and dexmedetomidine was intravenously infused at a loading dose of 05 μg∕kg over 15 min followed by an infusion of 05 μg·kg-1·h-1until the end of surgery at the same time. At 15 min before induction of anesthesia(T0), at the end of surgery(T1)and at 24, 48 and 72 h after surgery(T2-4), jugular bulb venous blood samples were taken for determination of concentrations of glutamate and aspartate in plasma(by reversed phase high-performance liquid chromatography)and β-AP(by enzyme-linked immunosorbent assay). Cognitive function was assessed at 1 day before surgery and 7 days after surgery using a battery of neuropsychologic tests including Wechsler Memory Scale, Digit Span (Forward and Backward), visual recognition and associative learning, Wechsler Adult Intelligence Scale and Trail Making Test Part A. The occurrence of postoperative cognitive dysfunction was recorded at 7 days after surgery. Results Compared with P and D groups, the concentrations of plasma glutamate at T2-3, plasma aspartate at T2and β-AP at T1and incidence of postoperative cognitive dysfunction were significantly decreased in group PD(P< 005). Conclusion The mechanism by which parecoxib sodium combined with dexmedetomidine decreases the occurrence of POCD may be related to inhibiting the levels of excitatory aminoacid and β-AP in brain tissues of elderly patients.
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Objective To study the effect of dimethyl fumarate (DMF) on Aβ-induced oxidative stress by regulating NF-E2-related factor 2 (Nrf2) expression and its mechanism.Methods Rat astrocytes were divided into Aβ group,DMF group,Nrf2 group and Nrf2 +DMF group.Expressions of Nrf2,Nqo1,Ho-1,Keap1 mRNA and HDAC were detected by RT-PCR and Western blot respectively.Results The expression levels of Nrf2,Nqo1 and HO-1 mRNA were significantly lower in Nrf2 group and Nrf2+DMF group than in Aβ group and DMF group (P＜0.05) and were significantly higher in DMF group than in Aβ group (P＜0.05) while the expression level of Keap1 mRNA was significantly lower in DMF group and Nrf2+DMF group than in Aβ group and Nrf2 group (P＜0.05).The expression level of HDAC was significantly lower in DMF group and Nrf2+DMF group than in Aβ group and Nrf2 group (6.41±0.43 vs 9.01±1.54,P＜0.05;6.72±0.30 vs 8.76± 0.74,P＜0.05).Conclusion DMF increases the Nrf2 expression by inhibiting the HDAC expression,thus reducing Aβ-induced oxidative stress in rat astrocytes.
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Objective To study effect of Radix Angelica Sinensis (RAS) on Alzhemier's Disease (AD)-like lesions in rats with chronic cerebral hypoperfusion (CCH).Methods rats were randomly divided into sham group,bilateral vascular occlusion (model group),low RAS dose treatment group and high RAS dose treatment group.Cognitive function was assessed by Morris Water Maze and Object Recognition Test.Aβ was detected by ELISA while brain-derived neurotrophic factor (BDNF)、β secretory enzyme 1 (BACE1)、phosphorylated Tau and phosphorylation of Akt/ GSK3β was detected by Western blot.Results There were shorter target quadrant exploration time (TQET),lower priority index (PI) 、phosphorylated Akt/GSK3β expression、BDNF and high-er Aβ1 40 、Aβ1-42 、p-Tau and BACE1 in model group than insham group (P＜0.05,P＜0.01).Low and high RAS dose treatment lengthened TQET,improved PI、phosphorylated Akt/GSK3β expression and BDNF while decreased Aβ1-40 、Aβ1-42 、p-Tau and BACE1 compared with model group.BDNF was higher after high dose RAS treatment than model group (P＜0.01).Conclusion RAS inhibits AD-like lesions in rats with CCH by downregulating the Akt/GSK3β pathway and BACE1 activity,thus improving the cognitive impairment.
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OBJECTIVE: Recently developed 18F-labelled amyloid beta (Aβ) positron emission tomography (PET) tracers have demonstrated potentials to enable more prevalent application of amyloid imaging in the clinical setting. The aim of this study is to demonstrate cerebral retention of Aβ in cognitively normal older adults, by implementing voxel-based analysis on images acquired from 18F-Florbetaben amyloid PET. METHODS: Fifty cognitive normal elderly subjects were recruited and included in the study. Demographic data and cognitive measurements were collected. Magnetic resonance imaging (MRI) and ¹⁸F-Florbetaben PET data were obtained followed by whole brain voxel-based analysis. RESULTS: Compared to the florbetaben (FBB) (−) counterpart, FBB (+) showed significantly higher Aβ deposition in the brain regions comprising anterior cingulate, middle cingulate, posterior cingulate and precuneus (family wise error corrected p < 0.05). There was no significant correlation between amyloid retention and cognitive functions. CONCLUSION: Our results confirms previous results regarding Aβ deposition by using ¹⁸F-Florbetaben, demonstrating potentials in application of 18F-Florbetaben PET imaging in clinical settings.
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Adult , Aged , Humans , Alzheimer Disease , Amyloid , Brain , Cognition , Gyrus Cinguli , Magnetic Resonance Imaging , Parietal Lobe , Positron-Emission TomographyABSTRACT
The most common neurodegenerative disease, Alzheimer disease (AD) constitutes the majority of all senile dementia cases. Extending life expectancy contributes to the increased incidence of AD, which is a serious threat to the quality of life of the elderly. The etiology and pathogenesis of AD are not absolutely clear. There are various kinds of hypotheses, such as abnormal phosphorylation of tau proteins, amyloid-beta protein toxicity, gene mutation, degeneration of cholinergic system, neuroinflammation, oxidative stress. Based on the above-mentioned theories, lots of studies of Uncaria Hook have been conducted in Alzheimer disease models. In this paper, we reviewed the latest research of Uncaria Hook on Alzheimer disease models to provide reference for further development of Uncaria Hook's medicinal potential.
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Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease.As the most common type of senile dementia disease,AD has no effective methods for early diagnoses.AD is characterized by the deposition of intracellular amyloid β (Aβ) plaques and extracellular neurofibrillary tangles (NFT) in the brain.In addition to allomnesia and cognitive disorder,ocular manifestation such as cataracts exists in AD patients.Studies have shown that amyloid-β (Aβ) is deposited not only in the brain but also in crystalline lens.For its structure and special location,crystalline len is more accessible for imaging than the brain,which can provide a simple,convenient and early diagnosis method for AD.Hence,it is worth investigating the relationship between Alzheimer's disease and cataracts.
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Objective To screen the amyloid protein-β(Aβ)degradation-associated genes through peripheral blood monocytes(PBMC)-extracted gene microarray analysis in patients with Alzheimer's disease(AD).Methods PBMC were isolated from blood of elderly AD patients versus age-matched healthy individuals(control).The cDNA(mRNAs)were analyzed using gene microarray.And real-time quantitative polymerase chain reaction detection and enzyme activity analysis were used to verify the primary outcome of gene chip.Results The expression of cathepsin D mRNA in peripheral blood monocytes was 104.70±15.96 in AD patients as compared with the control group 49.86±5.19,and the activity of cathepsin D was (22 620 ± 1 389) RFU in AD versus (32 210 ± 2 284) RFU in control (both P＜0.05).Conclusions The results suggest that the decreased levels of cathepsin D could be the stage markers related to the pathophysiology of AD process.Based on the microarray data,we select cathepsin D genes for further study.
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To observe the effect of puerarin on learning and memory function and tau phosphorylation in APP/PS1 transgenic mice, drugs were administered to 3-month old APP/PS1 transgenic mice. Learning and memory function of mice were assessed by Morris water maze test 3 months after treatment. Animals were decapitated after behavioral test. The levels of Aβ were detected by ELISA, the expression of protein [tau, phosphorylated tau, GSK3β and p-GSK3β(Ser9)] were assessed by Western blot. Morris water maze test showed that the escape latency of APP/PS1 double transgenic mice was significantly longer than that of the normal control group, and the residence time of the original quadrant was significantly shorter. The escape latency of puerarin group was significantly shorter and the residence time of the original quadrant was prolonged compared with the model group. Compared with the normal control group, the levels of Aβ in the cortex of APP/PS1 transgenic mice were increased, the expression of phosphorylated tau was significantly increased, and the expression of phosphorylated GSK3β(Ser9) protein was decreased. Treatment with puerarin, the latency of APP/PS1 transgenic mice was significantly reduced, the level of Aβ was decreased, the expression of phosphorylated tau was significantly decreased, and the expression of phosphorylated GSK3β(Ser9) protein was increased. Puerarin improves the learning and memory impairment by reducing the formation of Aβ, activating the GSK3β signaling pathway, inhibiting the phosphorylation of tau in APP/PS1 double transgenic mice.
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Objective To investigate the effects of type 2 diabetes on learning and memory of APP/PS1/Tau triple transgenic (3 × Tg) mice of Alzheimer’s disease, and the protective mechanism of liraglutide (LIR) thereof. Methods One month old C57BL/6 mice were set to be control group (WT). One month old 3×Tg mice were divided into control group (Tg), liraglutide group (Tg+LIR), type 2 diabetes group (Tg+T2DM) and liraglutide treatment group (Tg+T2DM+LIR). The model of T2DM was established by feeding the high fat and sugar fodder, and then injecting streptozotocin (STZ) in mice, making sure the fasting blood glucose was more than 7 mmol/L. Then the subcutaneous injection of LIR was administered for 2 months. The values of body weight and fasting blood glucose were detected at age of 5-month. Morris water maze was applied to evaluate the spatial learning and memory ability. Western blotting assay was used to measure the levels of phosphorylated Tau, neurofilament (NFs) and insulin receptor substrates. ELISA was used to detect the human Aβ42 to evaluate the effect of LIR on-amyloid. Results LIR can reduce body weight and blood glucose, can alleviate spatial learning and memory damaging caused by T2DM, and also can improve phosphorylated Tau levels, NFs and insulin receptor substrates caused by T2DM, and finally can reduce the deposition ofβ-amyloid of 3 × Tg mice. Conclusion T2DM can aggravate symptoms of AD in 3×Tg mice, and LIR has a protective effect on it.
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Objective To evaluate the accuracy of cerebrospinal fluid (CSF) amyloid beta 42 (Aβ-42) to tau level ratio (Aβ-42/tau) in predicting postoperative cognitive dysfunction (POCD) in elderly patients.Methods Eighty ASA physical status Ⅱ or Ⅲ patients of both sexes,aged 65-85 yr,undergoing elective total hip or knee replacement under combined spinal-epidural anesthesia,were enrolled in the study.Epidural catheter was placed at T3,4 interspace,and after a catheter was successfully placed into the subarachnoid space,CSF 2 ml was obtained to measure Aβ-42 and tau levels (units:pg/ml),and the ratio between them was calculated.Neuropsychological tests were performed at 1 day before surgery and 1 week after surgery.The Z score was used to identity POCD.The cut-off value for POCD and nonPOCD patients was determined by using ROC curve.Results Thirty-two patients were diagnosed with POCD,and the incidence was 40％.The Aβ-42/tau was 2.6±0.3 and 1.7±0.4 in non-POCD and POCD groups,respectively,and the ratio was significantly lower in POCD group than in non-POCD group.The sensitivity of CSF Aβ-42/tau in predicting POCD was 91.7％,the specificity was 81.2％,and Youden index was 0.7.ROC curves revealed that the cut-off value for POCD and non-POCD patients was 2.0.Conclusion CSF Aβ-42/tau can accurately predict the occurrence of POCD in elderly patients.