欧米伽-3 可缓解压力诱发的青少年抑郁症小鼠模型的行为和分子变化

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Tatyana Strekalova , Daniel Radford-Smith , Isobel K. Dunstan , Anna Gorlova , Evgeniy Svirin , Elisaveta Sheveleva , Alisa Burova , Sergey Morozov , Aleksey Lyundup , Gregor Berger , Daniel C. Anthony , Susanne Walitza
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引用次数: 0

摘要

导言:越来越多的青少年被诊断出患有抑郁症,因此需要采取特殊的预防和治疗方法。然而,目前还缺乏模拟青少年抑郁症的动物模型。本研究利用超声波(US)应激在幼年小鼠中探索了一种新的模型。方法我们在一个月大的C57/BL6小鼠中采用了US应激模型,将它们暴露于交替的超声波频率(20-25 kHz和25-45 kHz)中,持续三周。这些频率与啮齿动物的负面和中性情绪状态相对应,可诱发类似抑郁症的综合征。与此同时,小鼠接受含有二十碳五烯酸(EPA;0.55 毫克/千克/天)和二十二碳六烯酸(DHA;0.55 毫克/千克/天)的欧米加-3 食物补充剂(FS)或药物。应激后,我们评估了小鼠的焦虑和抑郁样行为、血液中皮质酮的水平、大脑中促炎细胞因子的表达,并对大脑、肝脏和血浆进行了代谢组分析。相比之下,US-FS 小鼠没有出现这些变化。补充 Omega-3 还能减少非应激小鼠的焦虑样行为。代谢组分析显示,US诱导了大脑能量代谢的变化,FS增加了大脑鞘磷脂。肝脏代谢同时受到 US 和 FS 的影响,而血浆代谢组的变化则是 FS 独有的。脑葡萄糖水平与焦虑测试中的活动呈正相关。这些效果可能源于补充剂的抗炎特性,表明它在青少年抑郁症方面具有潜在的治疗用途。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Omega-3 alleviates behavioral and molecular changes in a mouse model of stress-induced juvenile depression

Introduction

Depression is increasingly diagnosed in adolescence, necessitating specific prevention and treatment methods. However, there is a lack of animal models mimicking juvenile depression. This study explores a novel model using ultrasound (US) stress in juvenile mice.

Methods

We employed the US stress model in one-month-old C57/BL6 mice, exposing them to alternating ultrasound frequencies (20–25 kHz and 25–45 kHz) for three weeks. These frequencies correspond to negative and neutral emotional states in rodents and can induce a depressive-like syndrome. Concurrently, mice received either an omega-3 food supplement (FS) containing eicosapentaenoic acid (EPA; 0.55 mg/kg/day) and docosahexaenoic acid (DHA; 0.55 mg/kg/day) or a vehicle. Post-stress, we evaluated anxiety- and depressive-like behaviors, blood corticosterone levels, brain expression of pro-inflammatory cytokines, and conducted metabolome analysis of brain, liver and blood plasma.

Results

US-exposed mice treated with vehicle exhibited decreased sucrose preference, a sign of anhedonia, a key feature of depression, increased anxiety-like behavior, elevated corticosterone levels, and enhanced TNF and IL-1β gene expression in the brain. In contrast, US-FS mice did not display these changes. Omega-3 supplementation also reduced anxiety-like behavior in non-stressed mice. Metabolomic analysis revealed US-induced changes in brain energy metabolism, with FS increasing brain sphingomyelin. Liver metabolism was affected by both US and FS, while plasma metabolome changes were exclusive to FS. Brain glucose levels correlated positively with activity in anxiety tests.

Conclusion

Chronic omega-3 intake counteracted depressive- and anxiety-like behaviors in a US model of juvenile depression in mice. These effects likely stem from the anti-inflammatory properties of the supplement, suggesting potential therapeutic applications in juvenile depression.

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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.
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