中脑
类有机物
神经科学
类阿片
医学
多巴胺
芬太尼
生物
药理学
内科学
中枢神经系统
受体
作者
Hye Sung Kim,Yang Xiao,Xuejing Chen,Siyu He,Jongwon Im,Moshe J. Willner,Michael O. Finlayson,Cong Xu,Huixiang Zhu,Se Joon Choi,Eugene V. Mosharov,Hae‐Won Kim,Bin Xu,Kam W. Leong
标识
DOI:10.1002/advs.202400847
摘要
Understanding the impact of long-term opioid exposure on the embryonic brain is critical due to the surging number of pregnant mothers with opioid dependency. However, this has been limited by human brain inaccessibility and cross-species differences in animal models. Here, a human midbrain model is established that uses hiPSC-derived midbrain organoids to assess cell-type-specific responses to acute and chronic fentanyl treatment and fentanyl withdrawal. Single-cell mRNA sequencing of 25,510 cells from organoids in different treatment groups reveals that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters synaptic activity and neuron projection. In contrast, acute fentanyl treatment increases dopamine release but does not significantly alter gene expression related to cell lineage development. These results provide the first examination of the effects of opioid exposure on human midbrain development at the single-cell level.
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