基于人类干细胞的精神分裂症突触功能障碍和认知研究模型：叙事性综述。
Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review.
机构信息
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Chemical Biology and Therapeutic Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Chemical Biology and Therapeutic Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
出版信息
Schizophr Res. 2024 Nov;273:78-97. doi: 10.1016/j.schres.2023.02.029. Epub 2023 Mar 14.
Cognitive impairment is the strongest predictor of functional outcomes in schizophrenia and is hypothesized to result from synaptic dysfunction. However, targeting synaptic plasticity and cognitive deficits in patients remains a significant clinical challenge. A comprehensive understanding of synaptic plasticity and the molecular basis of learning and memory in a disease context can provide specific targets for the development of novel therapeutics targeting cognitive impairments in schizophrenia. Here, we describe the role of synaptic plasticity in cognition, summarize evidence for synaptic dysfunction in schizophrenia and demonstrate the use of patient derived induced-pluripotent stem cells for studying synaptic plasticity in vitro. Lastly, we discuss current advances and future technologies for bridging basic science research of synaptic dysfunction with clinical and translational research that can be used to predict treatment response and develop novel therapeutics.
认知障碍是精神分裂症功能结局的最强预测因子，其被假设是由于突触功能障碍所致。然而，针对患者的突触可塑性和认知缺陷仍然是一个重大的临床挑战。在疾病背景下全面了解突触可塑性以及学习和记忆的分子基础，可以为开发针对精神分裂症认知障碍的新型治疗方法提供特定靶点。在这里，我们描述了突触可塑性在认知中的作用，总结了精神分裂症中突触功能障碍的证据，并展示了使用患者来源的诱导多能干细胞在体外研究突触可塑性的方法。最后，我们讨论了将突触功能障碍的基础科学研究与可用于预测治疗反应和开发新型治疗方法的临床和转化研究联系起来的当前进展和未来技术。
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