Dwivedi Ila, Haddad Gabriel G
Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, United States.
Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, United States.
Front Cell Neurosci. 2024 May 15;18:1403326. doi: 10.3389/fncel.2024.1403326. eCollection 2024.
Over the past two decades, Opioid Use Disorder (OUD) among pregnant women has become a major global public health concern. OUD has been characterized as a problematic pattern of opioid use despite adverse physical, psychological, behavioral, and or social consequences. Due to the relapsing-remitting nature of this disorder, pregnant mothers are chronically exposed to exogenous opioids, resulting in adverse neurological and neuropsychiatric outcomes. Collateral fetal exposure to opioids also precipitates severe neurodevelopmental and neurocognitive sequelae. At present, much of what is known regarding the neurobiological consequences of OUD and prenatal opioid exposure (POE) has been derived from preclinical studies in animal models and postnatal or postmortem investigations in humans. However, species-specific differences in brain development, variations in subject age/health/background, and disparities in sample collection or storage have complicated the interpretation of findings produced by these explorations. The ethical or logistical inaccessibility of human fetal brain tissue has also limited direct examinations of prenatal drug effects. To circumvent these confounding factors, recent groups have begun employing induced pluripotent stem cell (iPSC)-derived brain organoid technology, which provides access to key aspects of cellular and molecular brain development, structure, and function . In this review, we endeavor to encapsulate the advancements in brain organoid culture that have enabled scientists to model and dissect the neural underpinnings and effects of OUD and POE. We hope not only to emphasize the utility of brain organoids for investigating these conditions, but also to highlight opportunities for further technical and conceptual progress. Although the application of brain organoids to this critical field of research is still in its nascent stages, understanding the neurobiology of OUD and POE via this modality will provide critical insights for improving maternal and fetal outcomes.
在过去二十年中，孕妇阿片类物质使用障碍（OUD）已成为全球主要的公共卫生问题。OUD的特征是尽管存在不良的身体、心理、行为和/或社会后果，但仍存在阿片类物质使用的问题模式。由于这种疾病的复发-缓解性质，怀孕母亲长期暴露于外源性阿片类物质，导致不良的神经和神经精神后果。胎儿接触阿片类物质也会引发严重的神经发育和神经认知后遗症。目前，关于OUD和产前阿片类物质暴露（POE）的神经生物学后果的许多已知信息来自动物模型的临床前研究以及人类的产后或死后调查。然而，大脑发育中的物种特异性差异、受试者年龄/健康/背景的变化以及样本采集或储存的差异使这些探索产生的结果的解释变得复杂。人类胎儿脑组织在伦理或后勤方面难以获取也限制了对产前药物作用的直接检查。为了规避这些混杂因素，最近一些研究小组开始采用诱导多能干细胞（iPSC）衍生的脑类器官技术，该技术提供了了解细胞和分子大脑发育、结构和功能关键方面的途径。在这篇综述中，我们努力总结脑类器官培养的进展，这些进展使科学家能够模拟和剖析OUD和POE的神经基础及影响。我们不仅希望强调脑类器官在研究这些情况方面的实用性，还希望突出进一步技术和概念进展的机会。尽管脑类器官在这一关键研究领域的应用仍处于起步阶段，但通过这种方式了解OUD和POE的神经生物学将为改善母婴结局提供关键见解。
