单核RNA测序揭示了重度抑郁症患者前额皮质代谢失调。

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Xiang-Yao Li, Yingbo Rao, Guo-Hao Li, Luxi He, Yaohan Wang, Wenli He, Ping Fang, Chenyu Pei, Lun Xi, Haiyan Xie, Yun-Rong Lu
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引用次数: 0

摘要

重度抑郁症(MDD)是一种广泛存在的精神疾病,被认为是2008年全球疾病负担的第三大原因。在MDD的背景下,前额叶皮层(PFC)突触传递的改变与PFC失活有关,PFC失活是认知功能和情绪调节的关键因素。鉴于中枢神经系统的高能量需求,这些突触变化提示MDD患者PFC内的代谢不平衡。然而,这种代谢失调的细胞机制仍未完全阐明。本研究采用单核RNA测序(snRNA-seq)数据预测MDD患者背外侧PFC (DLPFC)的代谢改变。我们的分析揭示了细胞类型特异性代谢模式,特别是MDD患者DLPFC中氧化磷酸化和碳水化合物代谢的破坏。基于人类表型本体论的基因集富集分析预测了MDD患者血清乳酸水平的改变,与47名年龄匹配的健康对照(hc)相比,MDD患者乳酸水平的降低证实了这一点。这项转录分析为与MDD相关的代谢紊乱和DLPFC失活背后的能量动力学提供了新的见解。这些发现有助于理解重度抑郁症的病理生理学,并可能指导创新治疗策略的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-nucleus RNA sequencing uncovers metabolic dysregulation in the prefrontal cortex of major depressive disorder patients.

Major depressive disorder (MDD) is a widespread psychiatric condition, recognized as the third leading cause of global disease burden in 2008. In the context of MDD, alterations in synaptic transmission within the prefrontal cortex (PFC) are associated with PFC hypoactivation, a key factor in cognitive function and mood regulation. Given the high energy demands of the central nervous system, these synaptic changes suggest a metabolic imbalance within the PFC of MDD patients. However, the cellular mechanisms underlying this metabolic dysregulation remain not fully elucidated. This study employs single-nucleus RNA sequencing (snRNA-seq) data to predict metabolic alterations in the dorsolateral PFC (DLPFC) of MDD patients. Our analysis revealed cell type-specific metabolic patterns, notably the disruption of oxidative phosphorylation and carbohydrate metabolism in the DLPFC of MDD patients. Gene set enrichment analysis based on human phenotype ontology predicted alterations in serum lactate levels in MDD patients, corroborated by the observed decrease in lactate levels in MDD patients compared to 47 age-matched healthy controls (HCs). This transcriptional analysis offers novel insights into the metabolic disturbances associated with MDD and the energy dynamics underlying DLPFC hypoactivation. These findings are instrumental for comprehending the pathophysiology of MDD and may guide the development of innovative therapeutic strategies.

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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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