自体促肾上腺皮质激素和溶血磷脂酸缺乏症对长期暴露于不可预测的轻度应激的小鼠抑郁样行为的影响

IF 4.3 2区 医学 Q1 NEUROSCIENCES Neurobiology of Stress Pub Date : 2024-04-04 DOI:10.1016/j.ynstr.2024.100632
Chao Wang , Ningyuan Li , Yuqi Feng , Siqi Sun , Jingtong Rong , Xin-hui Xie , Shuxian Xu , Zhongchun Liu
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引用次数: 0

摘要

脂质参与抑郁症的机理引发了广泛的讨论。早期的研究发现,抑郁症患者体内溶血磷脂酸(LPA)和自体免疫球蛋白(ATX)的水平降低。然而,这一现象对抑郁症的确切意义仍无定论。本研究试图探索这些观察结果的深层含义。我们评估了对照组和慢性不可预测轻度应激(CUMS)模型组中 ATX 和 LPA 的变化。此外,我们还通过对暴露于 CUMS 的小鼠进行行为测试,验证了向海马注射 ATX 腺相关病毒(AAV-ATX)的影响。此外,我们还探究了LPA对HT22细胞和小鼠海马内突触相关蛋白的影响。我们还进一步研究了 LPA 触发蛋白质表达变化的机制。用 ATX 增强海马组织,以评估其通过调节突触相关蛋白来减轻抑郁样行为的潜力。我们的研究结果表明,ATX和LPA水平的降低会改变体外和体内与突触可塑性相关的蛋白质的表达,如突触素I(SYN)、突触素(SYP)和脑源性神经营养因子(BDNF)。此外,我们还发现ERK/CREB 信号通路在介导 ATX 和 LPA 的作用方面发挥了作用。重要的是,战略性地补充 ATX 能有效缓解抑郁样行为。这项研究表明,ATX-LPA通路可能通过调节CUMS暴露小鼠大脑的突触可塑性来影响抑郁样行为。这些见解加深了我们对脂质代谢背景下抑郁症潜在致病机制的理解,并为改善这种疾病提出了有前景的治疗策略。
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Effects of autotaxin and lysophosphatidic acid deficiencies on depression-like behaviors in mice exposed to chronic unpredictable mild stress

The involvement of lipids in the mechanism of depression has triggered extensive discussions. Earlier studies have identified diminished levels of lysophosphatidic acid (LPA) and autotaxin (ATX) in individuals experiencing depression. However, the exact significance of this phenomenon in relation to depression remains inconclusive. This study seeks to explore the deeper implications of these observations. We assessed alterations in ATX and LPA in both the control group and the chronic unpredictable mild stress (CUMS) model group. Additionally, the impact of ATX adeno-associated virus (AAV-ATX) injection into the hippocampus was validated through behavioral tests in CUMS-exposed mice. Furthermore, we probed the effects of LPA on synapse-associated proteins both in HT22 cells and within the mouse hippocampus. The mechanisms underpinning the LPA-triggered shifts in protein expression were further scrutinized. Hippocampal tissues were augmented with ATX to assess its potential to alleviate depression-like behavior by modulating synaptic-related proteins. Our findings suggest that the decrement in ATX and LPA levels alters the expression of proteins associated with synaptic plasticity in vitro and in vivo, such as synapsin-I (SYN), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Moreover, we discerned a role for the ERK/CREB signaling pathway in mediating the effects of ATX and LPA. Importantly, strategic supplementation of ATX effectively mitigated depression-like behaviors. This study indicates that the ATX-LPA pathway may influence depression-like behaviors by modulating synaptic plasticity in the brains of CUMS-exposed mice. These insights augment our understanding of depression's potential pathogenic mechanism in the context of lipid metabolism and propose promising therapeutic strategies for ameliorating the disease.

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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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