Chronic Opioid Treatment Arrests Neurodevelopment and Alters Synaptic Activity in Human Midbrain Organoids
Abstract: 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.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Chronic Opioid Treatment Arrests Neurodevelopment and Alters Synaptic Activity in Human Midbrain Organoids ; day:28 ; month:03 ; year:2024 ; extent:16
Advanced science ; (28.03.2024) (gesamt 16)
- Creator
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Kim, Hye Sung
Xiao, Yang
Chen, Xuejing
He, Siyu
Im, Jongwon
Willner, Moshe J.
Finlayson, Michael O.
Xu, Cong
Zhu, Huixiang
Choi, Se Joon
Mosharov, Eugene V.
Kim, Hae‐Won
Xu, Bin
Leong, Kam
- DOI
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10.1002/advs.202400847
- URN
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urn:nbn:de:101:1-2024032913215845417450
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:46 AM CEST
Data provider
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Associated
- Kim, Hye Sung
- Xiao, Yang
- Chen, Xuejing
- He, Siyu
- Im, Jongwon
- Willner, Moshe J.
- Finlayson, Michael O.
- Xu, Cong
- Zhu, Huixiang
- Choi, Se Joon
- Mosharov, Eugene V.
- Kim, Hae‐Won
- Xu, Bin
- Leong, Kam
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