Aβ oligomers-induced toxicity is attenuated in cells cultured with NbActiv4™ medium.
Aβ oligomers-induced toxicity is attenuated in cells cultured with NbActiv4™ medium.
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DOI：
10.1007/s12640-012-9318-7
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发表时间：
2012-11
影响因子：
3.7
通讯作者：
Klein, William L.
中科院分区：
文献类型：
--
作者：
Zhou, Yan;Klein, William L.
致病性Aβ衍生的可扩散配体（ADDL）与突触后靶点结合，诱导过量的活性氧（ROS）并刺激培养的神经元中的tau过度磷酸化。最近，报道了NbAc-tiv 4 ™培养基增加培养的海马神经元中的神经元突触密度。我们的目的是研究这种新的培养基对ADDL诱导的毒性的影响。我们发现ADDL诱导的ROS在用NbActiv 4 ™培养的细胞中减弱。在通过不同饲养条件用NbActiv 4 ™培养的神经元中进行ADDL结合测定。每周一次用30%培养基饲养细胞，ADDL结合位点在体外（DIV）18天丰富。然而，每周更换一次50%培养基可使ADDL结合率降低约80%。NbActiv 4 ™产生的胶质细胞酸性蛋白（GFAP）阳性星形胶质细胞比广泛使用的海马培养基，补充有B27的neurobasal（neurobasal/B27）多约40%。据报道星形胶质细胞可产生多种营养因子，其中包括胰岛素样生长因子1（IGF-1）。一致地，当用NbActiv 4 ™培养时，神经元响应于ADDL攻击而对胰岛素/IGF-1信号传导的抑制剂敏感。总的来说，这项研究支持星形胶质细胞在神经保护中的重要作用，并表明针对星形胶质细胞功能障碍可能导致阿尔茨海默病的新治疗策略。
Pathogenic Aβ-derived diffusible ligands (ADDLs) bind to post-synaptic targets, induce excessive reactive oxygen species (ROS) and stimulate tau hyperphosphorylation in cultured neurons. Recently, NbAc-tiv4™ medium was reported to increase neuron synapse densities in cultured hippocampal neurons. We aimed to investigate the effect of this novel medium on ADDL-induced toxicity. We found that ADDL-induced ROS was attenuated in cells cultured with NbActiv4™. ADDL binding assay was performed in neurons cultured by different feeding conditions with NbActiv4™. Feeding cells with 30 % medium once a week, ADDL binding sites were abundant at days in vitro (DIV) 18. However, changing 50 % medium once a week decreased ADDL binding about 80 %. NbActiv4™ produced about 40 % more glial fibrillary acidic protein (GFAP) positive astrocytes than the widely used hippocampal culture medium, neurobasal supplemented with B27 (neurobasal/B27). Astrocytes are reported to produce kinds of trophic factors including insulin-like growth factor 1 (IGF-1). Consistently, when cultured with NbActiv4™, neurons were sensitive to inhibitors of insulin/IGF-1 signaling in response to ADDL attack. Overall, this study supports the important role of astrocytes in neuroprotection and indicates that targeting astrocytes dysfunction may lead to new therapeutic strategies for Alzheimer’s disease.
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影响因子：
5.3
作者：
Elmariah, SB;Crumling, MA;Balice-Gordon, RJ
通讯作者：
Balice-Gordon, RJ
影响因子：
4.8
作者：
De Felice, Fernanda G.;Velasco, Pauline T.;Klein, William L.
通讯作者：
Klein, William L.
影响因子：
64.8
作者：
Houstis, N;Rosen, ED;Lander, ES
通讯作者：
Lander, ES
影响因子：
4.7
作者：
Lambert, MP;Viola, KL;Klein, WL
通讯作者：
Klein, WL
DOI：
10.1073/pnas.95.11.6448
发表时间：
1998-05-26
影响因子：
11.1
作者：
Lambert, MP;Barlow, AK;Klein, WL
通讯作者：
Klein, WL