A proof of concept ‘phase zero’ study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology
| Autor: | Sneha Sudhakar Karanth, Michal Liput, Anirban Dutta, Mancheung Cheung, Michal K. Stachowiak, Mahasweta Bhattacharya, Justyna Augustyniak, Ewa K. Stachowiak |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Brain development Ubiquinone Induced Pluripotent Stem Cells Diseases Local field potential Proof of Concept Study Article Cell Line Choline Electron Transport Complex IV 03 medical and health sciences chemistry.chemical_compound Medical research Engineering 0302 clinical medicine Nuclear magnetic resonance medicine Organoid Humans Idebenone Spectroscopy Near-Infrared Multidisciplinary Thioctic Acid Chemistry Brain maturation Near-infrared spectroscopy Brain Mitochondria Electrophysiology Organoids 030104 developmental biology Neurology Case-Control Studies Schizophrenia Female Acetylcarnitine 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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