Asymptomatic neurotoxicity of amyloid beta-peptides (A beta(1-42) and A beta(25-35)) on mouse embryonic stem cell-derived neural cells
Document Type
Article
Publication Date
1-1-2021
Abstract
One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer's disease (AD), is to induce neurotoxicity by amyloid beta (A beta) peptides in suitable neural cells. Presently, data on the neurotoxicity of A beta in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with A beta peptides (A beta(1-42) and A beta(25-35)). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies in the absence of leukemia inhibitory factor, followed by the addition of all-trans retinoic acid as the neural inducer. Mature neuronal cells were exposed to different concentrations of A beta(1-42) and A beta(25-35) for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 mu M A beta(1-42) and 50 mu M A beta(25-35) only promoted 4096 and 1096, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the A beta peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and A beta peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies.
Keywords
Amyloid beta-peptides, Alzheimer's disease, Reactive oxygen species, Oxidative stress, 46C mouse embryonic stem cell
Divisions
fac_med
Funders
Ministry of Agriculture of Malaysia (MOA) through NKEA Research Grant Scheme (NRGS) [NH1014D045],Graduate Research Fellowship (GRF), Universiti Putra Malaysia (UPM)
Publication Title
Bosnian Journal of Basic Medical Science
Volume
21
Issue
1
Publisher
Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
Publisher Location
UNIV SARAJEVO, MEDICAL FAC, CEKALUSA, SARAJEVO 90, BOSNIA & HERCEG