Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells

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 (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differen...

Full description

Bibliographic Details
Main Authors: Mansor, Nur Izzati, Ntimi, Carolindah Makena, Abdul Aziz, Noraishah Mydin, Ling, King Hwa, Adam, Aishah, Rosli, Rozita, Hassan, Zurina, Nordin, Norshariza
Format: Article
Language:English
Published: Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2020
Online Access:http://psasir.upm.edu.my/id/eprint/87985/1/ABSTRACT.pdf
_version_ 1796981911745200128
author Mansor, Nur Izzati
Ntimi, Carolindah Makena
Abdul Aziz, Noraishah Mydin
Ling, King Hwa
Adam, Aishah
Rosli, Rozita
Hassan, Zurina
Nordin, Norshariza
author_facet Mansor, Nur Izzati
Ntimi, Carolindah Makena
Abdul Aziz, Noraishah Mydin
Ling, King Hwa
Adam, Aishah
Rosli, Rozita
Hassan, Zurina
Nordin, Norshariza
author_sort Mansor, Nur Izzati
collection UPM
description 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 (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ 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 Aβ peptides (Aβ1-42 and Aβ25-35). 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 Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 µM Aβ1-42 and 50 µM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ 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 Aβ 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.
first_indexed 2024-03-06T10:44:35Z
format Article
id upm.eprints-87985
institution Universiti Putra Malaysia
language English
last_indexed 2024-03-06T10:44:35Z
publishDate 2020
publisher Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
record_format dspace
spelling upm.eprints-879852022-05-24T07:33:28Z http://psasir.upm.edu.my/id/eprint/87985/ Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells Mansor, Nur Izzati Ntimi, Carolindah Makena Abdul Aziz, Noraishah Mydin Ling, King Hwa Adam, Aishah Rosli, Rozita Hassan, Zurina Nordin, Norshariza 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 (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ 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 Aβ peptides (Aβ1-42 and Aβ25-35). 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 Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 µM Aβ1-42 and 50 µM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ 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 Aβ 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. Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2020 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/87985/1/ABSTRACT.pdf Mansor, Nur Izzati and Ntimi, Carolindah Makena and Abdul Aziz, Noraishah Mydin and Ling, King Hwa and Adam, Aishah and Rosli, Rozita and Hassan, Zurina and Nordin, Norshariza (2020) Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells. Bosnian Journal of Basic Medical Sciences, 21 (1). pp. 1-13. ISSN 1840-4812 https://www.bjbms.org/ojs/index.php/bjbms/article/view/4639 10.17305/bjbms.2020.4639
spellingShingle Mansor, Nur Izzati
Ntimi, Carolindah Makena
Abdul Aziz, Noraishah Mydin
Ling, King Hwa
Adam, Aishah
Rosli, Rozita
Hassan, Zurina
Nordin, Norshariza
Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells
title Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells
title_full Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells
title_fullStr Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells
title_full_unstemmed Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells
title_short Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells
title_sort asymptomatic neurotoxicity of amyloid β peptides aβ1 42 and aβ25 35 on mouse embryonic stem cell derived neural cells
url http://psasir.upm.edu.my/id/eprint/87985/1/ABSTRACT.pdf
work_keys_str_mv AT mansornurizzati asymptomaticneurotoxicityofamyloidbpeptidesab142andab2535onmouseembryonicstemcellderivedneuralcells
AT ntimicarolindahmakena asymptomaticneurotoxicityofamyloidbpeptidesab142andab2535onmouseembryonicstemcellderivedneuralcells
AT abdulaziznoraishahmydin asymptomaticneurotoxicityofamyloidbpeptidesab142andab2535onmouseembryonicstemcellderivedneuralcells
AT lingkinghwa asymptomaticneurotoxicityofamyloidbpeptidesab142andab2535onmouseembryonicstemcellderivedneuralcells
AT adamaishah asymptomaticneurotoxicityofamyloidbpeptidesab142andab2535onmouseembryonicstemcellderivedneuralcells
AT roslirozita asymptomaticneurotoxicityofamyloidbpeptidesab142andab2535onmouseembryonicstemcellderivedneuralcells
AT hassanzurina asymptomaticneurotoxicityofamyloidbpeptidesab142andab2535onmouseembryonicstemcellderivedneuralcells
AT nordinnorshariza asymptomaticneurotoxicityofamyloidbpeptidesab142andab2535onmouseembryonicstemcellderivedneuralcells