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Quantitative and Qualitative Analysis of Neurotransmitter and Neurosteroid Production in Cerebral Organoids during Differentiation

Sung Bum Park, Byumseok Koh, Hyun Soo Kwon, Young Eun Kim, Seong Soon Kim, Sung‐Hee Cho, Tae‐Young Kim, Myung Ae Bae, Dukjin Kang, Chul Hoon Kim, Ki Young Kim

2023ACS Chemical Neuroscience14 citationsDOIOpen Access PDF

Abstract

In the human brain, neurophysiological activity is modulated by the movement of neurotransmitters and neurosteroids. To date, the similarity between cerebral organoids and actual human brains has been evaluated using comprehensive multiomics approaches. However, a systematic analysis of both neurotransmitters and neurosteroids from cerebral organoids has not yet been reported. Here, we performed quantitative and qualitative assessments of neurotransmitters and neurosteroids over the course of cerebral organoid differentiation. Our multiomics approaches revealed that the expression levels of neurotransmitter-related proteins and RNA, including neurosteroids, increase as cerebral organoids mature. We also found that the electrophysiological activity of human cerebral organoids increases in tandem with the expression levels of both neurotransmitters and neurosteroids. Our study demonstrates that the expression levels of neurotransmitters and neurosteroids can serve as key factors in evaluating the maturity and functionality of human cerebral organoids.

Topics & Concepts

Neuroactive steroidOrganoidNeuroscienceHuman brainNeurotransmitterBiologyChemistryCentral nervous systemBiochemistryReceptorGABAA receptorReceptor Mechanisms and SignalingNeuroscience and Neuropharmacology ResearchLipid Membrane Structure and Behavior