発育中の胎児にとって飲酒は安全ではない、アルコールが発育中の脳オルガノイドの成長と機能に害を与えることを分子レベルで示す新しい研究結果 No amount of alcohol consumption is safe for a developing fetus; a new study presents in molecular detail how alcohol harms growth and functioning of developing brain organoids
2022-11-18 カリフォルニア大学サンディエゴ校(UCSD)
胎児の脳発達のさまざまな時期にアルコールにさらされると、細胞プロセスの根本的な機能不全から、脳構造の構築不全、支持細胞(グリア形成)や脳細胞間の結合(シナプス形成)の不十分な形成まで、それぞれ異なるが必ずマイナスの影響が生じる。
さらに、電気生理学的な記録により、大脳皮質オルガノイドの電気活動パターンをモニターし、大脳皮質オルガノイドの機能障害を記録・確認した。
この研究結果は、動物モデルを用いたこれまでの研究を上回るものであると、著者らは述べている。
<関連情報>
- https://today.ucsd.edu/story/brain-organoids-reveal-in-detail-the-harms-of-prenatal-alcohol-exposure
- https://www.nature.com/articles/s41380-022-01862-7
アルコール暴露がヒト皮質オルガノイドの神経発達とネットワーク形成に与える影響 Impact of alcohol exposure on neural development and network formation in human cortical organoids
Jason W. Adams,Priscilla D. Negraes,Justin Truong,Timothy Tran,Ryan A. Szeto,Bruno S. Guerra,Roberto H. Herai,Carmen Teodorof-Diedrich,Stephen A. Spector,Miguel Del Campo,Kenneth L. Jones,Alysson R. Muotri & Cleber A. Trujillo
Molecular Psychiatry Published:16 November 2022
DOI:https://doi.org/10.1038/s41380-022-01862-7
Abstract
Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons. EtOH exposure produced temporally dependent cellular effects on proliferation, cell cycle, and apoptosis. In addition, we identified EtOH-induced alterations in post-translational histone modifications and chromatin accessibility, leading to impairment of cAMP and calcium signaling, glutamatergic synaptic development, and astrocytic function. Proteomic spatial profiling of cortical organoids showed region-specific, EtOH-induced alterations linked to changes in cytoskeleton, gliogenesis, and impaired synaptogenesis. Finally, multi-electrode array electrophysiology recordings confirmed the deleterious impact of EtOH on neural network formation and activity in cortical organoids, which was validated in primary human fetal tissues. Our findings demonstrate progress in defining the human molecular and cellular phenotypic signatures of prenatal alcohol exposure on functional neurodevelopment, increasing our knowledge for potential therapeutic interventions targeting FASD symptoms.
