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A proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology
Homeostatic control of neuronal excitability by modulation of synaptic inhibition (I) and excitation (E) of the principal neurons is important during brain maturation. The fundamental features of in-utero brain development, including local synaptic E–I ratio and bioenergetics, can be modeled by cere...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710726/ https://www.ncbi.nlm.nih.gov/pubmed/33268815 http://dx.doi.org/10.1038/s41598-020-77929-8 |
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author | Dutta, Anirban Karanth, Sneha Sudhakar Bhattacharya, Mahasweta Liput, Michal Augustyniak, Justyna Cheung, Mancheung Stachowiak, Ewa K. Stachowiak, Michal K. |
author_facet | Dutta, Anirban Karanth, Sneha Sudhakar Bhattacharya, Mahasweta Liput, Michal Augustyniak, Justyna Cheung, Mancheung Stachowiak, Ewa K. Stachowiak, Michal K. |
author_sort | Dutta, Anirban |
collection | PubMed |
description | Homeostatic control of neuronal excitability by modulation of synaptic inhibition (I) and excitation (E) of the principal neurons is important during brain maturation. The fundamental features of in-utero brain development, including local synaptic E–I ratio and bioenergetics, can be modeled by cerebral organoids (CO) that have exhibited highly regular nested oscillatory network events. Therefore, we evaluated a 'Phase Zero' clinical study platform combining broadband Vis/near-infrared(NIR) spectroscopy and electrophysiology with studying E–I ratio based on the spectral exponent of local field potentials and bioenergetics based on the activity of mitochondrial Cytochrome-C Oxidase (CCO). We found a significant effect of the age of the healthy controls iPSC CO from 23 days to 3 months on the CCO activity (chi-square (2, N = 10) = 20, p = 4.5400e−05), and spectral exponent between 30–50 Hz (chi-square (2, N = 16) = 13.88, p = 0.001). Also, a significant effect of drugs, choline (CHO), idebenone (IDB), R-alpha-lipoic acid plus acetyl-l-carnitine (LCLA), was found on the CCO activity (chi-square (3, N = 10) = 25.44, p = 1.2492e−05), spectral exponent between 1 and 20 Hz (chi-square (3, N = 16) = 43.5, p = 1.9273e−09) and 30–50 Hz (chi-square (3, N = 16) = 23.47, p = 3.2148e−05) in 34 days old CO from schizophrenia (SCZ) patients iPSC. We present the feasibility of a multimodal approach, combining electrophysiology and broadband Vis–NIR spectroscopy, to monitor neurodevelopment in brain organoid models that can complement traditional drug design approaches to test clinically meaningful hypotheses. |
format | Online Article Text |
id | pubmed-7710726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77107262020-12-03 A proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology Dutta, Anirban Karanth, Sneha Sudhakar Bhattacharya, Mahasweta Liput, Michal Augustyniak, Justyna Cheung, Mancheung Stachowiak, Ewa K. Stachowiak, Michal K. Sci Rep Article Homeostatic control of neuronal excitability by modulation of synaptic inhibition (I) and excitation (E) of the principal neurons is important during brain maturation. The fundamental features of in-utero brain development, including local synaptic E–I ratio and bioenergetics, can be modeled by cerebral organoids (CO) that have exhibited highly regular nested oscillatory network events. Therefore, we evaluated a 'Phase Zero' clinical study platform combining broadband Vis/near-infrared(NIR) spectroscopy and electrophysiology with studying E–I ratio based on the spectral exponent of local field potentials and bioenergetics based on the activity of mitochondrial Cytochrome-C Oxidase (CCO). We found a significant effect of the age of the healthy controls iPSC CO from 23 days to 3 months on the CCO activity (chi-square (2, N = 10) = 20, p = 4.5400e−05), and spectral exponent between 30–50 Hz (chi-square (2, N = 16) = 13.88, p = 0.001). Also, a significant effect of drugs, choline (CHO), idebenone (IDB), R-alpha-lipoic acid plus acetyl-l-carnitine (LCLA), was found on the CCO activity (chi-square (3, N = 10) = 25.44, p = 1.2492e−05), spectral exponent between 1 and 20 Hz (chi-square (3, N = 16) = 43.5, p = 1.9273e−09) and 30–50 Hz (chi-square (3, N = 16) = 23.47, p = 3.2148e−05) in 34 days old CO from schizophrenia (SCZ) patients iPSC. We present the feasibility of a multimodal approach, combining electrophysiology and broadband Vis–NIR spectroscopy, to monitor neurodevelopment in brain organoid models that can complement traditional drug design approaches to test clinically meaningful hypotheses. Nature Publishing Group UK 2020-12-02 /pmc/articles/PMC7710726/ /pubmed/33268815 http://dx.doi.org/10.1038/s41598-020-77929-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dutta, Anirban Karanth, Sneha Sudhakar Bhattacharya, Mahasweta Liput, Michal Augustyniak, Justyna Cheung, Mancheung Stachowiak, Ewa K. Stachowiak, Michal K. A proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology |
title | A proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology |
title_full | A proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology |
title_fullStr | A proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology |
title_full_unstemmed | A proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology |
title_short | A proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology |
title_sort | proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with vis/near-infrared spectroscopy and electrophysiology |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710726/ https://www.ncbi.nlm.nih.gov/pubmed/33268815 http://dx.doi.org/10.1038/s41598-020-77929-8 |
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