Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer's disease.
Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer's disease.
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DOI：
10.1186/s13024-017-0228-2
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发表时间：
2017-11-14
影响因子：
15.1
通讯作者：
Gan WB
中科院分区：
文献类型：
--
作者：
Bai Y;Li M;Zhou Y;Ma L;Qiao Q;Hu W;Li W;Wills ZP;Gan WB
阿尔茨海默病(AD)的特征是淀粉样蛋白沉积、缠结形成以及突触丢失。突触异常在阿尔茨海默病发病早期即可发生。识别早期突触异常及其潜在机制可能对AD的预防和治疗具有重要意义。我们采用体内双光子钙离子成像技术检测APPswe/PS1dE9小鼠AD模型和年龄匹配的野生型对照小鼠初级运动皮质2/3层锥体神经元胞体、树突和树突棘的活性。我们还进行了钙成像，以确定Aβ寡聚体对树突状钙活性的影响。此外，结构和功能双光子成像被用来检查AD模型小鼠树突状细胞钙活性异常和树突状突棘大小变化之间的联系。我们发现，3月龄APPswe/PS1dE9小鼠在安静休息时，初级运动皮质中2/3层神经元的体细胞钙活性显著低于野生型小鼠，但在跑步机上跑步时并不明显。值得注意的是，在AD小鼠的跑步机运动过程中，2/3层锥体神经元顶端树突的比例显著增加，显示出异常长持续时间和高峰值幅度的钙瞬变。向野生型小鼠脑内注射Aβ寡聚体也可在跑步过程中诱导异常的树突状钙瞬变。此外，我们还发现，在AD小鼠中，伴随着异常延长的树突状钙瞬变，树突棘的活性和大小显著减少。我们的发现表明，在APPswe/PS1dE9小鼠AD模型的运动皮质中，异常的树突状钙瞬变和突触去增强发生在淀粉样斑块形成之前。可溶性A-β寡聚体可诱导异常长时间、高幅度的树突状钙瞬变，在AD的早期发病机制中参与突触缺陷。本文的在线版本(10.1186/s130240170228-2)包含补充材料，可供授权用户使用。
Alzheimer’s disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention and treatment of AD. We performed in vivo two-photon calcium imaging to examine the activities of somas, dendrites and dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex in the APPswe/PS1dE9 mouse model of AD and age-matched wild type control mice. We also performed calcium imaging to determine the effect of Aβ oligomers on dendritic calcium activity. In addition, structural and functional two-photon imaging were used to examine the link between abnormal dendritic calcium activity and changes in dendritic spine size in the AD mouse model. We found that somatic calcium activities of layer 2/3 neurons were significantly lower in the primary motor cortex of 3-month-old APPswe/PS1dE9 mice than in wild type mice during quiet resting, but not during running on a treadmill. Notably, a significantly larger fraction of apical dendrites of layer 2/3 pyramidal neurons showed calcium transients with abnormally long duration and high peak amplitudes during treadmill running in AD mice. Administration of Aβ oligomers into the brain of wild type mice also induced abnormal dendritic calcium transients during running. Furthermore, we found that the activity and size of dendritic spines were significantly reduced on dendritic branches with abnormally prolonged dendritic calcium transients in AD mice. Our findings show that abnormal dendritic calcium transients and synaptic depotentiation occur before amyloid plaque formation in the motor cortex of the APPswe/PS1dE9 mouse model of AD. Dendritic calcium transients with abnormally long durations and high amplitudes could be induced by soluble Aβ oligomers and contribute to synaptic deficits in the early pathogenesis of AD. The online version of this article (10.1186/s13024-017-0228-2) contains supplementary material, which is available to authorized users.
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DOI：
10.1196/annals.1379.003
发表时间：
2007-01-01
期刊：
IMAGING AND THE AGING BRAIN
影响因子：
--
作者：
Grutzendler, Jaime;Helmin, Kathryn;Gan, Wen-Biao
通讯作者：
Gan, Wen-Biao
DOI：
10.1073/pnas.1206171109
发表时间：
2012-05-29
影响因子：
11.1
作者：
Busche, Marc Aurel;Chen, Xiaowei;Konnerth, Arthur
通讯作者：
Konnerth, Arthur
影响因子：
25
作者：
Busche, Marc Aurel;Kekus, Maja;Konnerth, Arthur
通讯作者：
Konnerth, Arthur
影响因子：
4.8
作者：
Christensen, RA;Shtifman, A;Querfurth, HW
通讯作者：
Querfurth, HW
DOI：
10.1016/s1050-3862(96)00167-2
发表时间：
1996-12-01
期刊：
GENETIC ANALYSIS-BIOMOLECULAR ENGINEERING
影响因子：
--
作者：
Borchelt, DR;Davis, J;Price, DL
通讯作者：
Price, DL