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11.
应用免疫组化方法 ,观察对照组、糖尿病组和糖尿病APP1 7肽治疗组小鼠脑内Tau蛋白的分布 ,以探讨APP1 7肽对糖尿病小鼠脑神经元Tau蛋白表达的影响。结果 :用Tau 1单染 ,正常小鼠脑及APP1 7肽治疗的糖尿病小鼠脑压后颗粒皮质及海马阳性反应神经元数目多。糖尿病小鼠只有用蛋白磷酸酯酶 (PP 2B)脱磷酸后阳性反应神经元数目及染色程度才与正常组接近。提示 :糖尿病小鼠脑内正常Tau蛋白表达障碍 ,有过度磷酸化 ,而APP1 7肽可改善Tau蛋白过度磷酸化 相似文献
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目的 探讨电针对SAMP8 小鼠行为学及淀粉样前体蛋白( amyloid precursor protein, APP) 和APP切割酶1(B site APP cleaving enzyme1, BACE-1)的影响,为临床治疗阿尔茨海默病病提供新的途径。 方法 将快速老化模型小鼠(SAMP8) 60只随机分成模型组、电针组和西药组,每组20只,正常老化小鼠 (SAMR1) 20只作为正常组。电针组电针刺激“百会”、 “肾俞”、“内关”、“大椎”穴;西药物组给予石杉碱甲 0.02 mg/kg剂量灌胃;正常组和模型组不给予治疗。治疗 20 d 后,用 Morris 水迷宫检测小鼠学习记忆能力,免疫组化定性检测小鼠海马APP和 BACE-1蛋白的表达,进一步实时荧光定量 PCR法测定APP mRNA和 BACE-1 mRNA 的表达。 结果 与模型组比较,西药组与电针组逃避潜伏期缩短,有效区停留时间和及跨越平台次数均显著增加(P<0.05),电针组APP mRNA 和 BACE-1 mRNA 相对表达量显著减少(P<0.05) 。 结论 电针可能抑制 SAMP8 小鼠脑内APP mRNA and BACE-1 mRNA表达,减少Aβ 生成,改善其学习记忆障碍。 相似文献
15.
李轶 《中华医学图书情报杂志》2015,24(12):63-65
对目前国内常见的问诊类移动医疗APP软件进行了分类,并基于用户应用体验分析评价了不同类别的问诊类移动医疗APP的功能,对问诊类移动医疗APP的开发应用前景进行了展望。 相似文献
16.
Elaine Delvaux Karen Bentley Victoria Stubbs Marwan Sabbagh Paul D. Coleman 《Neurobiology of aging》2013
Because amyloid precursor protein (APP) fragments exist in many tissues throughout the body, including the fluid compartments of blood, they have been the focus of numerous investigations into their potential as a biomarker of Alzheimer's disease. Using immunohistochemistry, immunoelectron microscopy, Western blot, and quantitative real-time-polymerase chain reaction (qRT-PCR) analysis we examined whether APP processing in leukocytes is analogous to APP processing in the brain. We show APP immunoreactivity at light and electron microscopic levels in the cytoplasm and nucleus of peripheral blood leukocytes (PBL) yet our Western blot analysis data demonstrated that brain and PBL contain different APP fragments and differentially expressed APP processing enzymes. A Disintegrin and Metalloproteinase domain 10 (ADAM10), nicastrin, and beta-secretase 2 (BACE2) were present in brain but were undetected in PBL. Presenilin 1 and beta-secretase 1 (BACE1) were detected in both tissues but showed different patterns in Western blots. Quantitative PCR results identified Neprilysin as the only processing enzyme we interrogated in which Western and quantitative PCR data coincided. Although our data on differential processing of APP in brain and PBL point to exercising caution when generalizing between blood and brain with regard to mechanisms, they have no implications regarding utility as biomarkers. 相似文献
17.
Paolo Paganetti Julia Reichwald Dorothee Bleckmann Dorothee Abramowski Domenico Ammaturo Carmen Barske Simone Danner Maurizio Molinari Matthias Müller Stéphanie Papin Sabine Rabe Peter Schmid Matthias Staufenbiel 《Neurobiology of aging》2013,34(12):2866-2878
Heterologous expression of the functional amyloid beta (Aβ) antibody β1 in the central nervous system was engineered to maximize antibody exposure in the brain and assess the effects on Aβ production and accumulation in these conditions. A single open reading frame encoding the heavy and light chains of β1 linked by the mouth and foot virus peptide 2A was expressed in brain neurons of transgenic mice. Two of the resulting BIN66 transgenic lines were crossed with APP23 mice, which develop severe central amyloidosis. Brain concentrations at steady-state 5 times greater than those found after peripheral β1 administration were obtained. Similar brain and plasma β1 concentrations indicated robust antibody efflux from the brain. In preplaque mice, β1 formed a complex with Aβ that caused a modest Aβ increase in brain and plasma. At 11 months of age, β1 expression reduced amyloid by 97% compared with age-matched APP23 mice. Interference of β1 with β-secretase cleavage of amyloid precursor protein was relatively small. Our data suggest that severely impaired amyloid formation was primarily mediated by a complex of β1 with soluble Aβ, which might have prevented Aβ aggregation or favored transport out of the brain. 相似文献
18.
Patrick J. Cimino Yue Yang Xianwu Li Jake F. Hemingway Makenzie K. Cherne Shawn B. Khademi Yoshinori Fukui Kathleen S. Montine Thomas J. Montine C. Dirk Keene 《Experimental and molecular pathology》2013
Alzheimer's disease (AD) neuropathology is characterized by innate immune activation primarily through prostaglandin E2 (PGE2) signaling. Dedicator of cytokinesis 2 (DOCK2) is a guanyl nucleotide exchange factor expressed exclusively in microglia in the brain and is regulated by PGE2 receptor EP2. DOCK2 modulates microglia cytokine secretion, phagocytosis, and paracrine neurotoxicity. EP2 ablation in experimental AD results in reduced oxidative damage and amyloid beta (Aβ) burden. This discovery led us to hypothesize that genetic ablation of DOCK2 would replicate the anti-Aβ effects of loss of EP2 in experimental AD. To test this hypothesis, we crossed mice that lacked DOCK2 (DOCK2 −/−), were hemizygous for DOCK2 (DOCK2 +/−), or that expressed two DOCK2 genes (DOCK2 +/+) with APPswe-PS1Δe9 mice (a model of AD). While we found no DOCK2-dependent differences in cortex or in hippocampal microglia density or morphology in APPswe-PS1Δe9 mice, cerebral cortical and hippocampal Aβ plaque area and size were significantly reduced in 10-month-old APPswe-PS1Δe9/DOCK2 −/− mice compared with APPswe-PS1Δe9/DOCK2 +/+ controls. DOCK2 hemizygous APPswe-PS1Δe9 mice had intermediate Aβ plaque levels. Interestingly, soluble Aβ42 was not significantly different among the three genotypes, suggesting the effects were mediated specifically in fibrillar Aβ. In combination with earlier cell culture results, our in vivo results presented here suggest DOCK2 contributes to Aβ plaque burden via regulation of microglial innate immune function and may represent a novel therapeutic target for AD. 相似文献
19.
Jack Rivers-Auty Victor S. Tapia Claire S. White Michael J.D. Daniels Samuel Drinkall Paul T. Kennedy Harry G. Spence Shi Yu Jack P. Green Christopher Hoyle James Cook Amy Bradley Alison E. Mather Ruth Peters Te-Chen Tzeng Margaret J. Gordon John H. Beattie David Brough Catherine B. Lawrence 《The Journal of neuroscience》2021,41(13):3025
Alzheimer''s disease is a devastating neurodegenerative disease with a dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing Alzheimer''s disease. Zinc deficiency is the most prevalent malnutrition in the world and may be a risk factor for Alzheimer''s disease potentially through enhanced inflammation, although evidence for this is limited. Here we provide epidemiological evidence suggesting that zinc supplementation was associated with reduced risk and slower cognitive decline, in people with Alzheimer''s disease and mild cognitive impairment. Using the APP/PS1 mouse model of Alzheimer''s disease fed a control (35 mg/kg zinc) or diet deficient in zinc (3 mg/kg zinc), we determined that zinc deficiency accelerated Alzheimer''s-like memory deficits without modifying amyloid β plaque burden in the brains of male mice. The NLRP3-inflammasome complex is one of the most important regulators of inflammation, and we show here that zinc deficiency in immune cells, including microglia, potentiated NLRP3 responses to inflammatory stimuli in vitro, including amyloid oligomers, while zinc supplementation inhibited NLRP3 activation. APP/PS1 mice deficient in NLRP3 were protected against the accelerated cognitive decline with zinc deficiency. Collectively, this research suggests that zinc status is linked to inflammatory reactivity and may be modified in people to reduce the risk and slow the progression of Alzheimer''s disease.SIGNIFICANCE STATEMENT Alzheimer''s disease is a common condition mostly affecting the elderly. Zinc deficiency is also a global problem, especially in the elderly and also in people with Alzheimer''s disease. Zinc deficiency contributes to many clinical disorders, including immune dysfunction. Inflammation is known to contribute to the risk and progression of Alzheimer''s disease; thus, we hypothesized that zinc status would affect Alzheimer''s disease progression. Here we show that zinc supplementation reduced the prevalence and symptomatic decline in people with Alzheimer''s disease. In an animal model of Alzheimer''s disease, zinc deficiency worsened cognitive decline because of an enhancement in NLRP3-driven inflammation. Overall, our data suggest that zinc status affects Alzheimer''s disease progression, and that zinc supplementation could slow the rate of cognitive decline. 相似文献
20.
To date, most studies of Shc family of signaling adaptor proteins have been focused on the near-ubiquitously expressed ShcA, indicating its relevance to age-related diseases and longevity. Although the role of the neuronal ShcC protein is much less investigated, accumulated evidence suggests its importance for neuroprotection against such aging-associated conditions as brain ischemia and oxidative stress. Here, we summarize more than decade of studies on the ShcC expression and function in normal brain, age-related brain pathologies and immune disorders with a focus on the interactions of ShcC with signaling proteins/pathways, and the possible implications of these interactions for changes associated with aging. 相似文献