德国马克斯·普朗克精神病学研究所Elisabeth B. Binder等研究人员合作发现，对人类眶额皮层进行的单核转录组学分析揭示衰老和精神疾病的趋同效应。2024年9月3日，《自然—神经科学》杂志在线发表了这项成果。

研究人员通过对87名有精神疾病诊断和无精神疾病诊断的个体的眶额皮层中约80万个细胞核进行转录组学分析，表征了与年龄相关的大脑转录组变化，并在一个包括32名个体的独立队列中重复了这些发现。衰老影响所有细胞类型，其中LAMP5⁺LHX6⁺中间神经元（在灵长类动物中丰富）受到的影响最大。

突触传递的破坏被发现是衰老组织中受影响的一个共同路径。年龄相关的转录组变化与阿尔茨海默病中的变化在多种细胞类型中存在重叠。研究人员发现精神疾病个体的转录组衰老加速的证据，并展示了衰老与精神病理学在多个细胞类型中的趋同特征。该研究揭示了年龄相关变化和精神病诊断驱动效应的细胞类型特异性影响及其生物学路径。

据介绍，衰老是一个复杂的生物学过程，并且是神经退行性疾病的最大风险因素。精神疾病患者的神经退行性疾病风险也增加。

附：英文原文

Title: Single-nucleus transcriptomic profiling of human orbitofrontal cortex reveals convergent effects of aging and psychiatric disease

Author: Frhlich, Anna S., Gerstner, Nathalie, Gagliardi, Miriam, Kdel, Maik, Yusupov, Natan, Matosin, Natalie, Czamara, Darina, Sauer, Susann, Roeh, Simone, Murek, Vanessa, Chatzinakos, Chris, Daskalakis, Nikolaos P., Knauer-Arloth, Janine, Ziller, Michael J., Binder, Elisabeth B.

Issue&Volume: 2024-09-03

Abstract: Aging is a complex biological process and represents the largest risk factor for neurodegenerative disorders. The risk for neurodegenerative disorders is also increased in individuals with psychiatric disorders. Here, we characterized age-related transcriptomic changes in the brain by profiling ~800,000 nuclei from the orbitofrontal cortex from 87 individuals with and without psychiatric diagnoses and replicated findings in an independent cohort with 32 individuals. Aging affects all cell types, with LAMP5+LHX6+ interneurons, a cell-type abundant in primates, by far the most affected. Disrupted synaptic transmission emerged as a convergently affected pathway in aged tissue. Age-related transcriptomic changes overlapped with changes observed in Alzheimer’s disease across multiple cell types. We find evidence for accelerated transcriptomic aging in individuals with psychiatric disorders and demonstrate a converging signature of aging and psychopathology across multiple cell types. Our findings shed light on cell-type-specific effects and biological pathways underlying age-related changes and their convergence with effects driven by psychiatric diagnosis. Single-cell profiling in the human cortex reveals aging-associated transcriptomic changes across all brain cell types, which overlap with effects with Alzheimer’s disease and show a convergent signature with psychopathology across multiple cell types.

DOI: 10.1038/s41593-024-01742-z

Source: https://www.nature.com/articles/s41593-024-01742-z