基于SH-SY5Y细胞系的淀粉样蛋白β毒性导致的电生理特性改变的瞬态存活模型

Title:A Transient Survival Model of Alteration of Electrophysiological Properties Due to Amyloid Beta Toxicity Based on SH-SY5Y Cell Line

Volume: 17 Issue: 13

关键词: SH-SY5Y细胞系，膜片钳，视黄酸，脑源性神经营养因子，β淀粉样蛋白毒性，细胞培养。

摘要:

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.

Cite this article as:

A Transient Survival Model of Alteration of Electrophysiological Properties Due to Amyloid Beta Toxicity Based on SH-SY5Y Cell Line, Current Alzheimer Research 2020; 17 (13) . https://dx.doi.org/10.2174/1567205018666210212155750