Molecular Psychiatry ( IF 9.6 ) Pub Date : 2024-09-08 , DOI: 10.1038/s41380-024-02728-w João V Nani 1, 2 , Alysson R Muotri 3 , Mirian A F Hayashi 1, 2
Schizophrenia (SCZ) is a complex mental disorder characterized by a range of symptoms, including positive and negative symptoms, as well as cognitive impairments. Despite the extensive research, the underlying neurobiology of SCZ remain elusive. To overcome this challenge, the use of diverse laboratory modeling techniques, encompassing cellular and animal models, and innovative approaches like induced pluripotent stem cell (iPSC)-derived neuronal cultures or brain organoids and genetically engineered animal models, has been crucial. Immortalized cellular models provide controlled environments for investigating the molecular and neurochemical pathways involved in neuronal function, while iPSCs and brain organoids, derived from patient-specific sources, offer significant advantage in translational research by facilitating direct comparisons of cellular phenotypes between patient-derived neurons and healthy-control neurons. Animal models can recapitulate the different psychopathological aspects that should be modeled, offering valuable insights into the neurobiology of SCZ. In addition, invertebrates’ models are genetically tractable and offer a powerful approach to dissect the core genetic underpinnings of SCZ, while vertebrate models, especially mammals, with their more complex nervous systems and behavioral repertoire, provide a closer approximation of the human condition to study SCZ-related traits. This narrative review provides a comprehensive overview of the diverse modeling approaches, critically evaluating their strengths and limitations. By synthesizing knowledge from these models, this review offers a valuable source for researchers, clinicians, and stakeholders alike. Integrating findings across these different models may allow us to build a more holistic picture of SCZ pathophysiology, facilitating the exploration of new research avenues and informed decision-making for interventions.
中文翻译:
窥视心灵:使用模型揭开精神分裂症的秘密
精神分裂症 (SCZ) 是一种复杂的精神障碍,其特征是一系列症状,包括阳性和阴性症状,以及认知障碍。尽管进行了广泛的研究,但 SCZ 的潜在神经生物学仍然难以捉摸。为了克服这一挑战,使用各种实验室建模技术(包括细胞和动物模型)以及创新方法(如诱导多能干细胞 (iPSC) 衍生的神经元培养物或脑类器官和基因工程动物模型)至关重要。永生化细胞模型为研究神经元功能中涉及的分子和神经化学途径提供了受控环境,而来自患者特异性来源的 iPSC 和脑类器官通过促进患者来源的神经元和健康对照神经元之间的细胞表型的直接比较,在转化研究中具有显著优势。动物模型可以概括应该建模的不同精神病理学方面,为 SCZ 的神经生物学提供有价值的见解。此外,无脊椎动物的模型在遗传上易于处理,并为剖析 SCZ 的核心遗传基础提供了一种强大的方法,而脊椎动物模型,尤其是哺乳动物,具有更复杂的神经系统和行为库,为研究 SCZ 相关特征提供了更接近人类状况的方法。本叙述性综述全面概述了不同的建模方法,批判性地评估了它们的优点和局限性。通过综合这些模型中的知识,本综述为研究人员、临床医生和利益相关者提供了有价值的来源。 整合这些不同模型中的发现可能使我们能够构建更全面的 SCZ 病理生理学图景,促进探索新的研究途径和明智的干预措施决策。