Model-based investigation of elasticity and spectral exponent from atomic force microscopy and electrophysiology in normal versus Schizophrenia human cerebral organoids

Model-based investigation of elasticity and spectral exponent from atomic force microscopy and electrophysiology in normal versus Schizophrenia human cerebral organoids
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基于模型的原子力显微镜和电生理学研究正常与精神分裂症人脑类器官的弹性和光谱指数

DOI:
10.1109/embc48229.2022.9871376
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发表时间:
2022
期刊:
2022 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC
影响因子:
--
通讯作者:
Stachowiak, Michal K.
Stachowiak, Michal K.
中科院分区:
--
文献类型:
--
作者:
Dutta, Anirban;Biber, John;Bae, Yongho;Augustyniak, Justyna;Liput, Michal;Stachowiak, Ewa;Stachowiak, Michal K.

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电生理记录中存在的非周期信号,称为L/f神经噪声,其生理来源尚不清楚,但它已与健康和疾病有关。功率谱斜率In被认为与兴奋(E)和抑制(I)之间的动态平衡有关。我们的研究发现,与正常脑器官相比,从精神分裂症患者(SCZ)诱导的多能干细胞(IPSCs)中培养的人脑器官显示出与弹性改变相关的结构变化。此外,线粒体药物调节了SCZ的弹性,这与光谱指数的变化有关。因此,我们建立了一个将微管-肌动蛋白张力整体结构与弹性和噪声联系起来的机电模型。基于模型的分析表明,张拉整体结构中本构单元的数量和长度的减少降低了其弹性,使谱指数变得更负,而热白噪声会使其变得更负。根据微管肌动蛋白模型和结构(弹性)和功能(电生理)反应的串扰,推测SCZ的线粒体动力学异常与线粒体-细胞骨架相互作用的缺陷有关,线粒体的长距离运输是为了支持E/I平衡的突触活动。临床相关性-我们的实验数据和模型显示了人脑器官的机械弹性和电生理之间的结构-功能关系,这将SCZ患者与正常对照组区分开来。
The physiological origin of the aperiodic signal present in the electrophysiological recordings, called l/f neural noise, is unknown; nevertheless, it has been associated with health and disease. The power spectrum slope,in, has been postulated to be related to the dynamic balance between excitation (E) and inhibition (I). Our study found that human cerebral organoids grown from induced pluripotent stem cells (iPSCs) from Schizophrenia patients (SCZ) showed structural changes associated with altered elasticity compared to that of the normal cerebral organoids. Furthermore, mitochondrial drugs modulated the elasticity in SCZ that was found related to the changes in the spectral exponent. Therefore, we developed an electro-mechanical model that related the microtubular-actin tensegrity structure to the elasticity and thenoise. Model-based analysis showed that a decrease in the number and length of the constitutive elements in the tensegrity structure decreased its elasticity and made the spectral exponent more negative while thermal white noise will make.. Based on the microtubularactin model and the cross-talk in structural (elasticity) and functional (electrophysiology) response, aberrant mitochondrial dynamics in SCZ are postulated to be related to the deficits in mitochondrial-cytoskeletal interactions for long-range transport of mitochondria to support synaptic activity for E/I balance. Clinical Relevance—Our experimental data and modeling present a structure-function relationship between mechanical elasticity and electrophysiology of human cerebral organoids that differentiated SCZ patients from normal controls.
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