摘要
背景:基底前脑胆碱能细胞的丢失,海马胆碱能预测的主要来源都与阿尔茨海默氏病有关。 目的:探讨隔海马通路与tau蛋白病模型小鼠的联系和阐明胆碱能改变tau的相关机制。 方法:成人(6至8月龄)和老年(16个月至18个月龄)表达野生型的人类tau蛋白,tg601转基因小鼠,采用体外磁共振扩散张量成像(DTI)检查和2 [18F]氟脱氧葡萄糖正电子发射断层扫描(PET)。在内侧隔核(MS)对胆碱乙酰转移酶(ChAT)免疫阳性神经元进行体视学方法计算以及对6个脑区内Acetylcholinesterase(乙酰胆碱酯酶)活性和乙酰胆碱酯酶mRNA进行测定。 结果:体外DTI显示tg601小鼠海马各向异性分数(FA)流线数随着年龄增长下降。老年tg601小鼠间隔的FA值比非转基因小鼠低。基于体素的统计分析显示,FDG-PET低葡萄糖吸收区的存在与成人MS有关,并在老年小鼠海马齿状回区蔓延。 在MS,胆碱乙酰转移酶(ChAT)的数量在老年tg601小鼠阳性神经元中减少。乙酰胆碱酯酶的活性和乙酰胆碱酯酶的mRNA的T转录增高。 结论:在小鼠tauopathy模型中,膈中隔AChE的上调导致胆碱能隔-海马通路的选择性变性。
关键词: 乙基酰转移酶,胆碱乙酰转移酶,弥散张量成像,PET,隔-海马通路,Tau.。
Current Alzheimer Research
Title:Involvement of the Septo-Hippocampal Cholinergic Pathway in Association with Septal Acetylcholinesterase Upregulation in a Mouse Model of Tauopathy
Volume: 14 Issue: 1
Author(s): Yuko Hara, Yumiko Motoi, Keigo Hikishima, Hiroshi Mizuma, Hirotaka Onoe, Shin-Ei Matsumoto, Montasir Elahi and Hideyuki Okano, Shigeki Aoki, Nobutaka Hattori
Affiliation:
关键词: 乙基酰转移酶,胆碱乙酰转移酶,弥散张量成像,PET,隔-海马通路,Tau.。
摘要: Background: Cholinergic cell loss in the basal forebrain, the major source of hippocampal cholinergic projections, has been implicated in Alzheimer's disease.
Objective: To examine whether the septohippocampal pathway is involved in tauopathy model mice and to elucidate the tau-associated mechanism underlying cholinergic alteration. Methods: Adult (6 to 8 months old) and old (16 to 18 months old) transgenic mice expressing wild-type human tau, Tg601, were examined using Ex vivo diffusion tensor magnetic resonance imaging (DTI) and 2-[18F]fluoro- 2-deoxy-D-glucose positron emission tomography (FDG-PET). Choline acetyltransferase (ChAT)-positive neurons in the medial septum (MS) were counted by stereological methods. Acetylcholinesterase (AChE) activity and AChE mRNA in 6 brain regions were measured. Results: Ex vivo DTI revealed that the number of fractional anisotropy (FA) streamlines in the septohippocampal tract decreased with age in Tg601 mice. The FA value in the septum was lower in old Tg601 mice than in non-tg mice. A voxel-based statistical analysis of FDG-PET revealed the presence of low glucose uptake areas, involving the MS in adults, and spread over regions including the hippocampal dentate gyrus in old mice. In the MS, the number of choline acetyltransferase (ChAT)-positive neurons decreased in old Tg601 mice. AChE activity and AChE mRNA T transcripts were exclusively higher in the septum. Conclusion: The upregulation of AChE in the septum may result in the selective degeneration of the septohippocampal cholinergic pathway in the tauopathy mouse model.Export Options
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Yuko Hara, Yumiko Motoi, Keigo Hikishima, Hiroshi Mizuma, Hirotaka Onoe, Shin-Ei Matsumoto, Montasir Elahi and Hideyuki Okano, Shigeki Aoki, Nobutaka Hattori , Involvement of the Septo-Hippocampal Cholinergic Pathway in Association with Septal Acetylcholinesterase Upregulation in a Mouse Model of Tauopathy, Current Alzheimer Research 2017; 14 (1) . https://dx.doi.org/10.2174/1567205013666160602235800
DOI https://dx.doi.org/10.2174/1567205013666160602235800 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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