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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
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)

Urheber
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
10.1002/advs.202400847
URN
urn:nbn:de:101:1-2024032913215845417450
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
14.08.2025, 10:46 MESZ

Datenpartner

Dieses Objekt wird bereitgestellt von:
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.

Beteiligte

  • 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

Ähnliche Objekte (12)