Background: Accumulation of toxic strands of amyloid beta (AB), which cause neurofibrillary tangles and, ultimately, cell death, is suspected to be the main culprit behind clinical symptoms of Alzheimer’s disease. Although the mechanism of cell death due to AB accumulation is well known, the intermediate phase between the start of accumulation and cell death is less known and investigated, partially due to technical challenges in identifying partially affected cells.

Objective: First, we aimed to establish an in vitro model that would show resilience against AB toxicity. Then we used morphological, molecular and electrophysiological assays to investigate how the characteristics of the surviving cells changed after AB toxicity.

Methods: To investigate this phase, we used differentiation of SH-SY5Y neuroblastoma stem cells by Retinoic Acid (RA) and Brain Derived Neurotrophic Factor (BDNF) to establish an in vitro model which would be able to demonstrate various levels of resistance to AB toxicity. We utilized fluorescent microscopy and whole cell patch clamp recordings to investigate behavior of the model.

Results: We observed significantly higher morphological resilience against AB toxicity in cells which were differentiated by both Retinoic Acid and Brain Derived Neurotrophic Factor compared to Retinoic Acid only. However, the electrophysiological properties of the Retinoic Acid + Brain-Derived Neurotrophic Factor differentiated cells were significantly altered after AB treatment.

Conclusion: We established a transient survival model for AB toxicity and observed the effects of AB on transmembrane currents of differentiated neurons.

背景：β 淀粉样蛋白 (AB) 毒性链的积累被怀疑是导致阿尔茨海默病临床症状的主要罪魁祸首，它会导致神经原纤维缠结并最终导致细胞死亡。尽管 AB 积累导致细胞死亡的机制众所周知，但积累开始和细胞死亡之间的中间阶段鲜为人知和研究较少，部分原因是在识别部分受影响的细胞方面存在技术挑战。

目标：首先，我们旨在建立一个体外模型，该模型将显示出对 AB 毒性的恢复能力。然后我们使用形态学、分子学和电生理学分析来研究 AB 毒性后存活细胞的特征如何变化。

方法：为了研究这个阶段，我们使用视黄酸 (RA) 和脑源性神经营养因子 (BDNF) 对 SH-SY5Y 神经母细胞瘤干细胞的分化来建立一个体外模型，该模型能够证明对 AB 毒性的不同程度的抗性. 我们利用荧光显微镜和全细胞膜片钳记录来研究模型的行为。

结果：我们观察到，与仅视黄酸相比，由视黄酸和脑源性神经营养因子分化的细胞对 AB 毒性具有显着更高的形态弹性。然而，视黄酸 + 脑源性神经营养因子分化细胞的电生理特性在 AB 处理后显着改变。

结论：我们建立了AB毒性的瞬时存活模型，并观察了AB对分化神经元跨膜电流的影响。