跨物种分析发现海马线粒体应激反应是小鼠早期生活压力和人类抑郁症的共同机制

IF 4.3 2区 医学 Q1 NEUROSCIENCES Neurobiology of Stress Pub Date : 2024-05-14 DOI:10.1016/j.ynstr.2024.100643
Bente M. Hofstra , Emmy E. Hoeksema , Martien JH. Kas , Dineke S. Verbeek
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引用次数: 0

摘要

抑郁症或重度抑郁障碍给个人和社会都带来了沉重的负担,约有 10.8%的总人口受到抑郁症的影响。这种精神疾病每年导致约 80 万人死亡。遗传和环境因素(如早期生活压力(ELS))的结合增加了人类患抑郁症的风险,海马体在抑郁症的病理生理学中的作用也已得到证实。然而,人们对抑郁症的内在机制仍然知之甚少,因此缺乏有效的治疗方法。为了更好地了解抑郁症发病的核心机制,我们采用了跨物种设计来研究小鼠ELS和人类抑郁症的共同海马病理生理机制。通过母体分离范式对小鼠进行 ELS,然后对成年海马组织进行 RNA 测序分析。结果发现了与线粒体应激反应途径有关的持续转录变化,氧化磷酸化和蛋白质折叠是受母体分离影响的主要机制。值得注意的是,我们观察到的线粒体应激反应通路与从抑郁症患者海马组织中公开获得的 RNAseq 数据有明显的重叠。这种线粒体相关基因表达变化的跨物种一致性表明,线粒体应激可能在抑郁症的发病过程中起着关键作用。我们的研究结果凸显了海马线粒体应激反应作为抑郁症发病核心机制的潜在意义。我们还需要进一步的实验研究来加深对这些机制的理解。
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Cross-species analysis uncovers the mitochondrial stress response in the hippocampus as a shared mechanism in mouse early life stress and human depression

Depression, or major depressive disorder, poses a significant burden for both individuals and society, affecting approximately 10.8% of the general population. This psychiatric disorder leads to approximately 800,000 deaths per year. A combination of genetic and environmental factors such as early life stress (ELS) increase the risk for development of depression in humans, and a clear role for the hippocampus in the pathophysiology of depression has been shown. Nevertheless, the underlying mechanisms of depression remain poorly understood, resulting in a lack of effective treatments. To better understand the core mechanisms underlying the development of depression, we used a cross-species design to investigate shared hippocampal pathophysiological mechanisms in mouse ELS and human depression. Mice were subjected to ELS by a maternal separation paradigm, followed by RNA sequencing analysis of the adult hippocampal tissue. This identified persistent transcriptional changes linked to mitochondrial stress response pathways, with oxidative phosphorylation and protein folding emerging as the main mechanisms affected by maternal separation. Remarkably, there was a significant overlap between the pathways involved in mitochondrial stress response we observed and publicly available RNAseq data from hippocampal tissue of depressive patients. This cross-species conservation of changes in gene expression of mitochondria-related genes suggests that mitochondrial stress may play a pivotal role in the development of depression. Our findings highlight the potential significance of the hippocampal mitochondrial stress response as a core mechanism underlying the development of depression. Further experimental investigations are required to expand our understanding of these mechanisms.

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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
期刊最新文献
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