MEA計測による脳オルガノイドの電気活動評価

抄録

Brain organoids with three-dimensional structure and tissue-like function are highly demanded for brain disease research and drug evaluation. MEA measurements are an effective method to assess neurotoxicity of drugs based on electrical activity of in vitro neural networks. The standard method for MEA analysis is to analyze spikes in the frequency band of 500 Hz or higher, but we found that low frequency components below 500 Hz contained information on cerebral organoid function. Sudden and persistent seizure-like firing was observed with convulsant pentylenetetrazol administration, displaying a concentration dependent periodic activity with the low frequency component enhanced even in one oscillation characteristic. On the other hand, in the administration of anti-epilepsy drugs (AEDs), the frequency of oscillation decreased in a concentration dependent manner and the intensity of the frequency component in one oscillation also decreased. Frequency component analysis of brain organoids using MEA is a useful analysis method to assess neurotoxicity of drugs and to perform IVIVE in the future. We also detected the electrical activities of the brain organoid using a 236,880-electrodes CMOS-MEA with high-spatio-temporal resolution. We succeeded in capturing the propagation pattern inside the organoid by detecting the electrical activities of each neuron. It was found that CMOS-MEA can evaluate the compound response based on more detailed information. MEA measurement of brain organoids will also help explore the function of the organoid itself, study human brain developments, and treat various brain diseases.