摘要
转基因APPswe/PS1dE9小鼠建立的阿尔茨海默病模型表明,在开始4-5个月大的时候,不断积累的β-淀粉样蛋白碎片会导致淀粉样斑块的形成。认知缺陷一般出现在12个月左右,在这之前,在β-淀粉样蛋白片段的积累伴随着可检测的毒蕈碱传输受损。结果表明,高热量鱼油饲料长期饲喂转基因小鼠能提高其特定的行为参数。我们研究了用Fortasyn(含鱼油及支持膜更新的成分)、植物豆甾醇和鱼油以及单独豆甾醇三种不同高热量饲料进行短期(三周)饲喂对在5个月大的转基因小鼠和野生型小鼠海马胆碱能神经传递标记物的影响。与野生型小鼠比,正常饮食量饲喂的转基因小鼠表现为ChAT活性增加和卡巴胆碱刺激的 GTP-γ35S 结合减少。对于野生型小鼠,与控制组相比,实验用饲料对ChAT、AChE和 BuChE的活性、毒蕈碱受体密度和卡巴胆碱刺激的 GTP-γ35S 结合无影响。相反,对于转基因小鼠,所有的实验饲料能增加刺激GTP-γ35S 结合的卡巴胆碱的效能并使其达到野生型小鼠水平。只有Fortasyn能增加转基因小鼠胆碱能突触标记。数据表明,即使是用特定的脂质膳食补充剂短期喂养转基因小鼠,也能影响胆碱能神经突触的标记和矫正受损的M型信号转导。
关键词: G蛋白激活,海马,毒蕈碱受体的神经传递,营养,ω-3脂肪酸,甾醇
Current Alzheimer Research
Title:Lipid-Based Diets Improve Muscarinic Neurotransmission in the Hippocampus of Transgenic APPswe/PS1dE9 Mice
Volume: 12 Issue: 10
Author(s): Helena Janickova, Vladimir Rudajev, Eva Dolejsi, Hennariikka Koivisto, Jan Jakubik, Heikki Tanila, Esam E. El-Fakahany and Vladimir Dolezal
Affiliation:
关键词: G蛋白激活,海马,毒蕈碱受体的神经传递,营养,ω-3脂肪酸,甾醇
摘要: Transgenic APPswe/PS1dE9 mice modeling Alzheimer’s disease demonstrate ongoing accumulation of β-amyloid fragments resulting in formation of amyloid plaques that starts at the age of 4-5 months. Buildup of β-amyloid fragments is accompanied by impairment of muscarinic transmission that becomes detectable at this age, well before the appearance of cognitive deficits that manifest around the age of 12 months. We have recently demonstrated that long-term feeding of trangenic mice with specific isocaloric fish oil-based diets improves specific behavioral parameters. Now we report on the influence of short-term feeding (3 weeks) of three isocaloric diets supplemented with Fortasyn (containing fish oil and ingredients supporting membrane renewal), the plant sterol stigmasterol together with fish oil, and stigmasterol alone on markers of cholinergic neurotransmission in the hippocampus of 5-month-old transgenic mice and their wild-type littermates. Transgenic mice fed normal diet demostrated increase in ChAT activity and attenuation of carbachol-stimulated GTP-γ35S binding compared to wild-type mice. None of the tested diets compared to control diet influenced the activities of ChAT, AChE, BuChE, muscarinic receptor density or carbachol-stimulated GTP-γ35S binding in wild-type mice. In contrast, all experimental diets increased the potency of carbachol in stimulating GTP-γ35S binding in trangenic mice to the level found in wild-type animals. Only the Fortasyn diet increased markers of cholinergic synapses in transgenic mice. Our data demonstrate that even short-term feeding of transgenic mice with chow containing specific lipid-based dietary supplements can influence markers of cholinergic synapses and rectify impaired muscarinic signal transduction that develops in transgenic mice.
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Helena Janickova, Vladimir Rudajev, Eva Dolejsi, Hennariikka Koivisto, Jan Jakubik, Heikki Tanila, Esam E. El-Fakahany and Vladimir Dolezal , Lipid-Based Diets Improve Muscarinic Neurotransmission in the Hippocampus of Transgenic APPswe/PS1dE9 Mice, Current Alzheimer Research 2015; 12 (10) . https://dx.doi.org/10.2174/1567205012666151027130350
DOI https://dx.doi.org/10.2174/1567205012666151027130350 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
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Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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