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Methods. 2011 Mar;53(3):201-7. doi: 10.1016/j.ymeth.2010.12.009. Epub 2010 Dec 14.
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Novel mouse model of Alzheimer's disease exhibits pathology through synergistic interactions among amyloid-β, tau, and reactive astrogliosis.新型阿尔茨海默病小鼠模型通过淀粉样β蛋白、tau蛋白和反应性星形胶质细胞增生之间的协同相互作用表现出病理特征。
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[Alzheimer disease: cellular and molecular aspects].[阿尔茨海默病:细胞与分子层面]
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Label-free imaging of amyloid plaques in Alzheimer's disease with stimulated Raman scattering microscopy.利用受激拉曼散射显微镜对阿尔茨海默病中的淀粉样斑块进行无标记成像。
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APOE4-specific changes in Aβ accumulation in a new transgenic mouse model of Alzheimer disease.载脂蛋白 E4 特异性改变在阿尔茨海默病新型转基因小鼠模型中的 Aβ 积累。
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A Peephole into the Brain: Neuropathological Features of Alzheimer's Disease Revealed by in vivo Two-Photon Imaging.窥探大脑:活体双光子成像揭示的阿尔茨海默病神经病理学特征
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本文引用的文献

1
Intravital microscopy of the mouse brain microcirculation using a closed cranial window.使用封闭颅窗对小鼠脑微循环进行活体显微镜检查。
J Vis Exp. 2010 Nov 18(45):2184. doi: 10.3791/2184.
2
Caspase activation precedes and leads to tangles.半胱氨酸天冬氨酸蛋白酶的激活先于并导致缠结。
Nature. 2010 Apr 22;464(7292):1201-4. doi: 10.1038/nature08890. Epub 2010 Mar 31.
3
Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation.淀粉样蛋白β通过钙调神经磷酸酶的激活诱导形态神经退行性三联征,包括棘突丢失、树突简化和神经突营养不良。
J Neurosci. 2010 Feb 17;30(7):2636-49. doi: 10.1523/JNEUROSCI.4456-09.2010.
4
Divergent pathways mediate spine alterations and cell death induced by amyloid-beta, wild-type tau, and R406W tau.不同的信号通路介导由β-淀粉样蛋白、野生型tau蛋白和R406W tau蛋白诱导的树突棘改变和细胞死亡。
J Neurosci. 2009 Nov 18;29(46):14439-50. doi: 10.1523/JNEUROSCI.3590-09.2009.
5
A reporter of local dendritic translocation shows plaque- related loss of neural system function in APP-transgenic mice.局部树突转运的报告者显示APP转基因小鼠中与斑块相关的神经系统功能丧失。
J Neurosci. 2009 Oct 7;29(40):12636-40. doi: 10.1523/JNEUROSCI.1948-09.2009.
6
Fluorescent Arc/Arg3.1 indicator mice: a versatile tool to study brain activity changes in vitro and in vivo.荧光弧/Arg3.1 标记小鼠:一种用于研究体外和体内大脑活动变化的多功能工具。
J Neurosci Methods. 2009 Oct 30;184(1):25-36. doi: 10.1016/j.jneumeth.2009.07.015. Epub 2009 Jul 21.
7
Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window.通过慢性颅骨视窗对小鼠新皮层进行长期、高分辨率成像。
Nat Protoc. 2009;4(8):1128-44. doi: 10.1038/nprot.2009.89. Epub 2009 Jul 16.
8
Tangle-bearing neurons survive despite disruption of membrane integrity in a mouse model of tauopathy.在tau蛋白病小鼠模型中,尽管膜完整性遭到破坏,但含有缠结的神经元仍能存活。
J Neuropathol Exp Neurol. 2009 Jul;68(7):757-61. doi: 10.1097/NEN.0b013e3181a9fc66.
9
Matrix metalloproteinase inhibition reduces oxidative stress associated with cerebral amyloid angiopathy in vivo in transgenic mice.基质金属蛋白酶抑制可减轻转基因小鼠体内与脑淀粉样血管病相关的氧化应激。
J Neurochem. 2009 Jun;109(6):1636-47. doi: 10.1111/j.1471-4159.2009.06096.x. Epub 2009 Apr 8.
10
General anesthetics and the developing brain.全身麻醉与发育中的大脑。
Curr Opin Anaesthesiol. 2009 Jun;22(3):368-73. doi: 10.1097/aco.0b013e3283294c9e.

使用体内成像技术监测阿尔茨海默病小鼠模型中的蛋白质聚集和毒性。

Monitoring protein aggregation and toxicity in Alzheimer's disease mouse models using in vivo imaging.

机构信息

Massachusetts General Hospital/Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA.

出版信息

Methods. 2011 Mar;53(3):201-7. doi: 10.1016/j.ymeth.2010.12.009. Epub 2010 Dec 14.

DOI:10.1016/j.ymeth.2010.12.009
PMID:21163350
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3049845/
Abstract

Aggregation of amyloid beta peptide into senile plaques and hyperphosphorylated tau protein into neurofibrillary tangles in the brain are the pathological hallmarks of Alzheimer's disease. Despite over a century of research into these lesions, the exact relationship between pathology and neurotoxicity has yet to be fully elucidated. In order to study the formation of plaques and tangles and their effects on the brain, we have applied multiphoton in vivo imaging of transgenic mouse models of Alzheimer's disease. This technique allows longitudinal imaging of pathological aggregation of proteins and the subsequent changes in surrounding neuropil neurodegeneration and recovery after therapeutic interventions.

摘要

淀粉样 β 肽聚集形成老年斑,过度磷酸化的 tau 蛋白聚集形成神经原纤维缠结,这是阿尔茨海默病的病理特征。尽管对这些病变进行了一个多世纪的研究,但病理与神经毒性的确切关系尚未完全阐明。为了研究斑块和缠结的形成及其对大脑的影响,我们应用了阿尔茨海默病转基因小鼠模型的多光子在体成像技术。该技术允许对蛋白质的病理性聚集进行纵向成像,以及随后对周围神经突神经退行性变的变化和治疗干预后的恢复进行成像。