Host: The Japanese Society of Toxicology
Name : The 47th Annual Meeting of the Japanese Society of Toxicology
Date : 2020 -
Astrocyte and neural network activities are closely related. It has been reported that in evoking convulsions, astrocyte oscillation precedes neural activity. If an astrocyte response to a convulsant could be detected in an in vitro culture sample, this would be an effective method for predicting seizure liability of drugs. We investigated whether astrocyte oscillation could be detected using the MEA measurement, and whether a response to a convulsant could be detected based on astrocyte oscillations. Rat hippocampal astrocytes and neurons were seeded on MEA plates (Alpha med scientific), and a sample containing only astrocytes and a sample having a different ratio of neurons were constructed. To detect the astrocyte response, 4-AP was administered and the evoked response was measured. Picrotoxin, chlorpromazine, and pilocarpine were administered to co-cultured samples of human iPS cell-derived neurons and astrocytes (Axol) in order to examine whether astrocyte responses to convulsants having different mechanism of action were detected. Oscillation was detected by 4-AP administration in the astrocyte-only sample. In addition, the frequency intensity was increased in a dose-dependent manner with 4-AP. In an astrocyte co-cultured sample with a small percentage of neurons, it was observed that neural activity was induced after astrocyte oscillation. In samples with a high proportion of neurons, oscillation of astrocytes and neurons was observed almost simultaneously. From these results, it was found that astrocyte oscillation could be detected by MEA, and that astrocytes induced neural activity in advance. In a co-culture system of human iPS cell-derived astrocytes and neurons, picrotoxin, chlorpromazine and pilocarpine dose-dependently increased the frequency intensity below 1 Hz, which reflects astrocyte oscillation. The response of cultured astrocytes was detected for the first time using MEA. In addition, the response of astrocytes to convulsants was detected in a dose-dependent manner. The present study demonstrated the efficacy of a method for predicting seizure liability of drugs based on astrocyte responses.
