Multi-site dynamic recording for Aβ oligomers-induced Alzheimer's disease in vitro based on neuronal network chip

Gao, Fan; Gao, Keqiang; He, Chuanjiang; Liu, Mengxue; Wan, Hao; Wang, Ping

doi:10.1016/j.bios.2019.03.025

Cited by 29 publications

(10 citation statements)

References 35 publications

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“…A recently published study based on MEA recordings showed that one application of Aβ oligomers initially led to activation followed by further (after 12-24 h) suppression and desynchronization in neural network activity, ultimately resulting in network destruction ( Gao et al, 2019 ). In our work, we studied more prolonged effects caused by amyloid on neural network activity and identified a significant decrease.…”

Section: Discussionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor (BDNF) Preserves the Functional Integrity of Neural Networks in the β-Amyloidopathy Model in vitro

Митрошина

Yarkov

Mishchenko

et al. 2020

Front. Cell Dev. Biol.

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Alzheimer’s disease (AD) is a widespread chronic neurodegenerative pathology characterized by synaptic dysfunction, partial neuronal death, cognitive decline and memory impairments. The major hallmarks of AD are extracellular senile amyloid plaques formed by various types of amyloid proteins (Aβ) and the formation and accumulation of intracellular neurofibrillary tangles. However, there is a lack of relevant experimental models for studying changes in neural network activity, the features of intercellular signaling or the effects of drugs on the functional activity of nervous cells during AD development. In this work, we examined two experimental models of amyloidopathy using primary hippocampal cultures. The first model involves the embryonic brains of 5xFAD mice; the second uses chronic application of amyloid beta 1-42 (Aβ1-42). The model based on primary hippocampal cells obtained from 5xFAD mice demonstrated changes in spontaneous network calcium activity characterized by a decrease in the number of cells exhibiting Ca 2+ activity, a decrease in the number of Ca 2+ oscillations and an increase in the duration of Ca 2+ events from day 21 of culture development in vitro . Chronic application of Aβ1-42 resulted in the rapid establishment of significant neurodegenerative changes in primary hippocampal cultures, leading to marked impairments in neural network calcium activity and increased cell death. Using this model and multielectrode arrays, we studied the influence of amyloidopathy on spontaneous bioelectrical neural network activity in primary hippocampal cultures. It was shown that chronic Aβ application decreased the number of network bursts and spikes in a burst. The spatial structure of neural networks was also disturbed that characterized by reduction in both the number of key network elements (hubs) and connections between network elements. Moreover, application of brain-derived neurotrophic factor (BDNF) recombinant protein and BDNF hyperexpression by an adeno-associated virus vector partially prevented these amyloidopathy-induced neurodegenerative phenomena. BDNF maintained cell viability and spontaneous bioelectrical and calcium network activity in primary hippocampal cultures.

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Section: Discussionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor (BDNF) Preserves the Functional Integrity of Neural Networks in the β-Amyloidopathy Model in vitro

Митрошина

Yarkov

Mishchenko

et al. 2020

Front. Cell Dev. Biol.

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“…Also neurodegenerative disorders, such as AD, can be modeled in vitro on MEAs by treating healthy neuronal cultures to mimic the pathological condition. The most commonly used AD models are obtained through the application of amyloid-β (Aβ) peptides or oligomers, which play a well-recognized key-role in early AD pathophysiology, long before amyloid plaque formation and neurodegeneration occurring [141,148,159,222,223]. The use of a MEA-based model, by allowing to record the electrophysiological activity on the same population of cells over an extended period of time, enables to investigate both the acute and chronic neurotoxic effects of Aβ oligomers on neuronal network activity.…”

Section: Disease Modelingmentioning

confidence: 99%

The potential of in vitro neuronal networks cultured on micro electrode arrays for biomedical research

2023

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In vitro neuronal models have become an important tool to study healthy and diseased neuronal circuits. The growing interest of neuroscientists to explore the dynamics of neuronal systems and the increasing need to observe, measure and manipulate not only single neurons but populations of cells pushed for technological advancement. In this sense, Micro-Electrode Arrays (MEAs) emerged as a promising technique, made of cell culture dishes with embedded micro-electrodes allowing non-invasive and relatively simple measurement of the activity of neuronal cultures at the network level.In the past decade, MEAs popularity has rapidly grown. MEAs devices have been extensively used to measure the activity of neuronal cultures mainly derived from rodents. Rodent neuronal cultures on MEAs have been employed to investigate physiological mechanisms, study the effect of chemicals in neurotoxicity screenings, and model the electrophysiological phenotype of neuronal networks in different pathological conditions. With the advancements in human induced pluripotent stem cells (hiPSCs) technology, the differentiation of human neurons from the cells of adult donors became possible. hiPSCs-derived neuronal networks on MEAs have been employed to develop patient-specific in vitro platforms to characterize the pathophysiological phenotype and to test drugs, paving the way towards personalized medicine.In this review, we first describe MEAs technology and the information that can be obtained from MEAs recordings. Then, we give an overview of studies in which MEAs have been used in combination with different neuronal systems (i.e., rodent 2D and 3D neuronal cultures, organotypic brain slices, hiPSCs-derived 2D and 3D neuronal cultures, and brain organoids) for biomedical research, including physiology studies, neurotoxicity screenings, disease modeling, and drug testing. We end by discussing potential, challenges and future perspectives of MEAs technology, and providing some guidance for the choice of theneuronal model and MEAs device, experimental design, data analysis and reporting for scientific publications.

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“…Microelectrode arrays (MEAs) technology is a well-established tool to study how cellular composition, connectivity, genetic, and epigenetic expression correlate with the functional electrical activity expressed by in-vitro neuronal models [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. MEAs applicability ranges from drug/toxicological screening [ 1 , 5 , 9 ] to the characterization of various neuronal disorders [ 3 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. In particular, with the introduction of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, human-derived neuronal models could be created, potentially making the in-vitro approach more reliable and representative of in-vivo conditions.…”

Section: Introductionmentioning

confidence: 99%

Human-Derived Cortical Neurospheroids Coupled to Passive, High-Density and 3D MEAs: A Valid Platform for Functional Tests

et al. 2023

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With the advent of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, methods to create in-vitro human-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality (3D) would make them more representative of an in-vivo environment. Thus, human-derived 3D structures are becoming increasingly used for in-vitro disease modeling. Achieving control over the final cell composition and investigating the exhibited electrophysiological activity is still a challenge. Thence, methodologies to create 3D structures with controlled cellular density and composition and platforms capable of measuring and characterizing the functional aspects of these samples are needed. Here, we propose a method to rapidly generate neurospheroids of human origin with control over cell composition that can be used for functional investigations. We show a characterization of the electrophysiological activity exhibited by the neurospheroids by using micro-electrode arrays (MEAs) with different types (i.e., passive, C-MOS, and 3D) and number of electrodes. Neurospheroids grown in free culture and transferred on MEAs exhibited functional activity that can be chemically and electrically modulated. Our results indicate that this model holds great potential for an in-depth study of signal transmission to drug screening and disease modeling and offers a platform for in-vitro functional testing.

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Multi-site dynamic recording for Aβ oligomers-induced Alzheimer's disease in vitro based on neuronal network chip

Cited by 29 publications

References 35 publications

Brain-Derived Neurotrophic Factor (BDNF) Preserves the Functional Integrity of Neural Networks in the β-Amyloidopathy Model in vitro

Brain-Derived Neurotrophic Factor (BDNF) Preserves the Functional Integrity of Neural Networks in the β-Amyloidopathy Model in vitro

The potential of in vitro neuronal networks cultured on micro electrode arrays for biomedical research

Human-Derived Cortical Neurospheroids Coupled to Passive, High-Density and 3D MEAs: A Valid Platform for Functional Tests

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