发表一篇学和医学成像类SCI论文
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Abstract:
BACKGROUND:Overactivation of ryanodine receptors and the resulting impaired calcium homeostasis contribute to Alzheimer's disease-related pathophysiology. This study hypothesized that exposing neuronal progenitors derived from induced pluripotent stems cells of patients with Alzheimer's disease to dantrolene will increase survival, proliferation, neurogenesis, and synaptogenesis. METHODS:Induced pluripotent stem cells obtained from skin fibroblast of healthy subjects and patients with familial and sporadic Alzheimer's disease were used. Biochemical and immunohistochemical methods were applied to determine the effects of dantrolene on the viability, proliferation, differentiation, and calcium dynamics of these cells. RESULTS:Dantrolene promoted cell viability and proliferation in these two cell lines. Compared with the control, differentiation into basal forebrain cholinergic neurons significantly decreased by 10.7% (32.9 ± 3.6% vs. 22.2 ± 2.6%, N = 5, P = 0.004) and 9.2% (32.9 ± 3.6% vs. 23.7 ± 3.1%, N = 5, P = 0.017) in cell lines from sporadic and familial Alzheimer's patients, respectively, which were abolished by dantrolene. Synapse density was significantly decreased in cortical neurons generated from stem cells of sporadic Alzheimer's disease by 58.2% (237.0 ± 28.4 vs. 99.0 ± 16.6 arbitrary units, N = 4, P = 0.001) or familial Alzheimer's disease by 52.3% (237.0 ± 28.4 vs.113.0 ± 34.9 vs. arbitrary units, N = 5, P = 0.001), which was inhibited by dantrolene in the familial cell line. Compared with the control, adenosine triphosphate (30 µM) significantly increased higher peak elevation of cytosolic calcium concentrations in the cell line from sporadic Alzheimer's patients (84.1 ± 27.0% vs. 140.4 ± 40.2%, N = 5, P = 0.049), which was abolished by the pretreatment of dantrolene. Dantrolene inhibited the decrease of lysosomal vacuolar-type H-ATPase and the impairment of autophagy activity in these two cell lines from Alzheimer's disease patients. CONCLUSIONS:Dantrolene ameliorated the impairment of neurogenesis and synaptogenesis, in association with restoring intracellular Ca homeostasis and physiologic autophagy, cell survival, and proliferation in induced pluripotent stem cells and their derived neurons from sporadic and familial Alzheimer's disease patients. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Overactivation of ryanodine receptors in the endoplasmic reticulum and the resulting dysregulation of calcium homeostasis contribute to Alzheimer's disease-related pathophysiologyDantrolene is an antagonist of ryanodine receptors, and its chronic use has been suggested to improve memory function in experimental models of Alzheimer's disease WHAT THIS ARTICLE TELLS US THAT IS NEW: Survival, proliferation, and differentiation of neuronal progenitors derived from patients with Alzheimer's disease are impaired when compared with healthy counterpartsChronic exposure of induced pluripotent stem cells, derived from patients with Alzheimer's disease, to dantrolene improves the survival, proliferation, and differentiation of these cells.
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最新影响因子:8.986 | 期刊ISSN:0003-3022 | CiteScore:3.08 |
出版周期:Monthly | 是否OA:YES | 出版年份:1940 |
自引率:7.00% | 研究方向:医学-麻醉学 |
出版地区:UNITED STATES |
SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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Anesthesiology is the official Journal of the American Society of Anesthesiologists. It is widely regarded as the preeminent scientific journal in the specialty.
麻醉学是美国麻醉师协会的官方刊物。它被广泛认为是该专业最杰出的科学期刊。
大类(学科) | 小类(学科) | 学科排名 |
医学 |
ANESTHESIOLOGY (麻醉学) 1区 |
1/31 |
年度总发文量 | 年度论文发表量 | 年度综述发表量 |
165 | 157 | 8 |
引文计数(2018)
文献(2015-2017)
4377次引用
1421篇文献
序号 | 类别 | 排名 | 百分位 |
1 |
大类(学科):Medicine
小类(学科):Anesthesiology and Pain Medicine
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研究方向:CHEMISTRY, MULTIDISCIPLINARY-NANOSCIENCE & NANOTEC
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研究方向:CHEMISTRY, MULTIDISCIPLINARY-NANOSCIENCE & NANOTEC
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研究方向:CHEMISTRY, MULTIDISCIPLINARYMATERIALS SCIE-MATERIA
影响因子:2.024
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研究方向:工程技术-材料科学:综合
发表一篇学和医学成像类SCI论文
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