Chronic Opioid Treatment Arrests Neurodevelopment and Alters Synaptic Activity in Human Midbrain Organoids

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 W.

doi:10.1002/advs.202400847

Cited by 3 publications

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

BrainSTEM: A multi-resolution fetal brain atlas to assess the fidelity of human midbrain cultures

Toh,

Xu,

Chen

et al. 2024

Preprint

View full text Add to dashboard Cite

Many midbrain dopaminergic neuron (mDA) differentiation protocols aimed at Parkinson disease (PD) modeling and cell replacement therapy have been developed. However, comprehensive evaluations of the transcriptomic fidelity of these protocols at the single-cell level against a common in vivo reference have been lacking. To this end, we constructed an integrated human fetal whole-brain atlas and a midbrain subatlas to use as a standard of comparison. From the whole-brain atlas, we observed distinct brain-region-specific gene expression in most neural cell types, emphasizing the need to first evaluate in vitro protocols at the whole-brain level to identify midbrain-associated cells. These cells are then mapped to the midbrain subatlas for more refined neuronal subtype specification and trajectory analysis specific to the midbrain. We surveyed all publicly available single-cell datasets of human midbrain culture models and performed the two-tier mapping. Using this biologically-driven multi-resolution mapping strategy which we termed BrainSTEM (brain Single-cell Two tiEr Mapping), we confirmed the presence of multiple midbrain cell types (on-target), but also a substantial proportion of cells associated with non-midbrain regions and subtypes (off-target). This leads to an overall inflation of mDA presence, stemming from non-midbrain-associated cells, across all published protocols. BrainSTEM thus offers an unbiased framework for understanding the current state of midbrain models and aids the improvement of midbrain differentiation protocols for PD studies.

show abstract

BrainSTEM: A multi-resolution fetal brain atlas to assess the fidelity of human midbrain cultures

Toh,

Xu,

Chen

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Understanding the impact of the gut microbiome on opioid use disorder: Pathways, mechanisms, and treatment insights

Kazemian,

Pakpour

2024

Microbial Biotechnology

View full text Add to dashboard Cite

The widespread use of opioids for chronic pain management not only poses a significant public health issue but also contributes to the risk of tolerance, dependence, and addiction, leading to opioid use disorder (OUD), which affects millions globally each year. Recent research has highlighted a potential bidirectional relationship between the gut microbiome and OUD. This emerging perspective is critical, especially as the opioid epidemic intensifies, emphasizing the need to investigate how OUD may alter gut microbiome dynamics and vice versa. Understanding these interactions could reveal new insights into the mechanisms of addiction and tolerance, as well as provide novel approaches for managing and potentially mitigating OUD impacts. This comprehensive review explores the intricate bidirectional link through the gut–brain axis, focusing on how opiates influence microbial composition, functional changes, and gut mucosal integrity. By synthesizing current findings, the review aims to inspire new strategies to combat the opioid crisis and leverage microbiome‐centred interventions for preventing and treating OUD.

show abstract

Recent advances in brain organoids: a comprehensive review of the last eight years

Xiong,

Wang

2024

View full text Add to dashboard Cite

Organoids are three-dimensional cellular structures grown in vitro that can self-organize and differentiate into cell types with organ-specific functions, closely mimicking the biological properties of tissues and organs in vivo. Brain organoids, which differentiate into structures resembling brain function, serve as valuable models for medical research, including disease microenvironment simulation, brain mechanism exploration, and drug evaluation. In this review, we analyzed 808 articles retrieved from PubMed, CNKI, and Wanfang databases using the keyword "brain organoids," of which 180 were included. We summarized the research progress of brain organoids over the past eight years by categorizing and refining the findings. Our analysis shows that brain organoids have achieved significant success in simulating brain development in vitro, leading to the establishment and refinement of 3D brain organoid models for disease research. Brain organoids have been widely applied to explore disease-related mechanisms, yielding promising results and opening avenues for further research on the human brain. In this review, we summarize the progress of brain organoids in three areas: culture methods, disease-related research, and brain exploration.

show abstract

Chronic Opioid Treatment Arrests Neurodevelopment and Alters Synaptic Activity in Human Midbrain Organoids

Cited by 3 publications

References 115 publications

BrainSTEM: A multi-resolution fetal brain atlas to assess the fidelity of human midbrain cultures

BrainSTEM: A multi-resolution fetal brain atlas to assess the fidelity of human midbrain cultures

Understanding the impact of the gut microbiome on opioid use disorder: Pathways, mechanisms, and treatment insights

Recent advances in brain organoids: a comprehensive review of the last eight years

Contact Info

Product

Resources

About