A proof of concept 'phase zero' study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology.
A proof of concept 'phase zero' study of neurodevelopment using brain organoid models with Vis/near-infrared spectroscopy and electrophysiology.
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使用VIS/近红外光谱和电生理学的脑类器官模型对神经发育的概念验证。
DOI：
10.1038/s41598-020-77929-8
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发表时间：
2020-12-02
影响因子：
4.6
通讯作者：
Stachowiak MK
中科院分区：
文献类型：
--
作者：
Dutta A;Karanth SS;Bhattacharya M;Liput M;Augustyniak J;Cheung M;Stachowiak EK;Stachowiak MK
通过调节主要神经元的突触抑制 (I) 和兴奋 (E) 来实现神经元兴奋性的稳态控制在大脑成熟过程中非常重要。子宫内大脑发育的基本特征，包括局部突触 E-I 比和生物能学，可以通过表现出高度规则的嵌套振荡网络事件的大脑类器官 (CO) 进行建模。因此，我们评估了“零阶段”临床研究平台，该平台结合了宽带可见光/近红外 (NIR) 光谱和电生理学，并研究基于局部场电位的光谱指数的 E-I 比和基于线粒体细胞色素 C 氧化酶 (CCO) 活性的生物能学。我们发现健康对照 iPSC CO 的年龄从 23 天到 3 个月对 CCO 活性有显着影响（卡方 (2, N = 10) = 20, p = 4.5400e−05) 和 30–50 Hz 之间的光谱指数 (卡方 (2, N = 16) = 13.88, p = 0.001)。此外，还发现药物胆碱 (CHO)、艾地苯醌 (IDB)、R-α-硫辛酸加乙酰基-L-肉碱 (LCLA) 对 CCO 活性有显着影响（卡方 (3, N = 10) = 25.44，p = 1.2492e−05），光谱指数在 1 到 20 Hz 之间（卡方 (3, N = 16) = 43.5, p = 1.9273e−09) 和 30–50 Hz（卡方 (3, N = 16) = 23.47, p = 3.2148e−05），34 天前的 CO精神分裂症（SCZ）患者 iPSC。我们提出了结合电生理学和宽带可见-近红外光谱的多模式方法的可行性，以监测脑类器官模型中的神经发育，该模型可以补充传统的药物设计方法来测试有临床意义的假设。
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.
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影响因子：
16.2
作者：
Beckervordersandforth R;Ebert B;Schäffner I;Moss J;Fiebig C;Shin J;Moore DL;Ghosh L;Trinchero MF;Stockburger C;Friedland K;Steib K;von Wittgenstein J;Keiner S;Redecker C;Hölter SM;Xiang W;Wurst W;Jagasia R;Schinder AF;Ming GL;Toni N;Jessberger S;Song H;Lie DC
通讯作者：
Lie DC
影响因子：
16.2
作者：
Chen G;Zhang Y;Li X;Zhao X;Ye Q;Lin Y;Tao HW;Rasch MJ;Zhang X
通讯作者：
Zhang X
细胞外田地和电流的起源-EEG，ECOG，LFP和尖峰。
DOI：
10.1038/nrn3241
发表时间：
2012-05-18
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Buzsáki G;Anastassiou CA;Koch C
通讯作者：
Koch C
影响因子：
4.5
作者：
Albinana, E.;Luengo, J. G.;Hernandez-Guijo, J. M.
通讯作者：
Hernandez-Guijo, J. M.
影响因子：
3.4
作者：
Cserép C;Pósfai B;Schwarcz AD;Dénes Á
通讯作者：
Dénes Á