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在基于活动的厌食症模型中,慢性饥饿会导致小胶质细胞耗竭。

Chronic starvation induces microglial cell depletion in an activity-based anorexia model.

作者信息

Verspohl Valerie, van Egmond Miranda, Kneisel Lilly, Reese Friederike, Thelen Anna C, Korten Nele, Neumann Maren, Schaack Lena, Voelz Clara, Käver Larissa, Herpertz-Dahlmann Beate, Beyer Cordian, Seitz Jochen, Trinh Stefanie

机构信息

Institute of Neuroanatomy, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Neuenhofer Weg 21, 52074, Aachen, Germany.

出版信息

Sci Rep. 2025 Apr 23;15(1):14132. doi: 10.1038/s41598-025-98237-z.

DOI:10.1038/s41598-025-98237-z
PMID:40269196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12019532/
Abstract

Anorexia nervosa (AN) is a severe psychiatric disease with a largely unknown pathophysiology. AN leads to reduced brain volume and a disbalance of the gut microbiome suggesting the involvement of the gut-brain-axis. Also, in the activity-based anorexia (ABA) animal model mimicking AN brain volume loss is observed. This study investigated the impact of chronic starvation on brain cell populations and evaluated the potential protective effects of omega-3 fatty acids (FA) and probiotics in rats. We used a chronic ABA model and provided daily oral supplementation of omega-3 FA and probiotics. Immunohistochemistry and qPCR were used to analyze GFAP-positive astrocytes, IBA1-positive microglia, OLIG1/2-positive oligodendrocytes, MAP2-positive neurons and Ki-67-positive proliferating cells in the cerebral cortex and corpus callosum. We found a significant reduction of astrocytes and microglia in all ABA groups, likely due to reduced proliferating cells. Reduced running wheel activity and reduced amount of food needed to sustain body weight were observed in animals with supplementation with omega-3 FA and probiotics but we did not observe alterations in brain cells that could be attributed to these supplementations. Our results indicate that glial cell depletion potentially underlies the diminished brain volume found in ABA rats. Omega-3 FA and probiotics show potential for reducing AN-related symptoms and merit further study as a therapeutic approach.

摘要

神经性厌食症(AN)是一种严重的精神疾病,其病理生理学在很大程度上尚不明确。AN会导致脑容量减少以及肠道微生物群失衡,这表明肠道-脑轴参与其中。此外,在模拟AN的基于活动的厌食症(ABA)动物模型中也观察到了脑容量损失。本研究调查了慢性饥饿对脑细胞群体的影响,并评估了ω-3脂肪酸(FA)和益生菌对大鼠的潜在保护作用。我们使用了慢性ABA模型,并每日口服补充ω-3 FA和益生菌。采用免疫组织化学和qPCR分析大脑皮层和胼胝体中GFAP阳性星形胶质细胞、IBA1阳性小胶质细胞、OLIG1/2阳性少突胶质细胞、MAP2阳性神经元和Ki-67阳性增殖细胞。我们发现所有ABA组中的星形胶质细胞和小胶质细胞均显著减少,这可能是由于增殖细胞减少所致。在补充了ω-3 FA和益生菌的动物中观察到转轮活动减少以及维持体重所需食物量减少,但我们未观察到可归因于这些补充剂的脑细胞变化。我们的结果表明,胶质细胞耗竭可能是ABA大鼠脑容量减小的潜在原因。ω-3 FA和益生菌显示出减轻AN相关症状的潜力,作为一种治疗方法值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/12019532/0050459eea80/41598_2025_98237_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/12019532/c9fe28e0e512/41598_2025_98237_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/12019532/b51cde280f9e/41598_2025_98237_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/12019532/d01fab061e74/41598_2025_98237_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/12019532/0050459eea80/41598_2025_98237_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/12019532/c9fe28e0e512/41598_2025_98237_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/12019532/b51cde280f9e/41598_2025_98237_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/12019532/d01fab061e74/41598_2025_98237_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/12019532/0050459eea80/41598_2025_98237_Fig4_HTML.jpg

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本文引用的文献

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[New aspects in etiology and treatment of adolescent anorexia nervosa-a postulated bio-psycho-social model and the impact of the COVID-19 pandemic].青少年神经性厌食症病因与治疗的新进展——一种假定的生物-心理-社会模型及新冠疫情的影响
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2024 Apr;67(4):400-408. doi: 10.1007/s00103-024-03856-y. Epub 2024 Mar 18.
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Longitudinal analysis of the gut microbiome in adolescent patients with anorexia nervosa: microbiome-related factors associated with clinical outcome.青少年神经性厌食症患者肠道微生物组的纵向分析:与临床结局相关的微生物组相关因素。
Gut Microbes. 2024 Jan-Dec;16(1):2304158. doi: 10.1080/19490976.2024.2304158. Epub 2024 Jan 31.
3
Glial cell changes in the corpus callosum in chronically-starved mice.
长期饥饿小鼠胼胝体中的神经胶质细胞变化。
J Eat Disord. 2023 Dec 18;11(1):227. doi: 10.1186/s40337-023-00948-z.
4
ω-3 Polyunsaturated Fatty Acids Improve the Blood-Brain-Barrier Integrity in Contrast-Induced Blood-Brain-Barrier Injury in Uremic Mice.ω-3 多不饱和脂肪酸可改善尿毒症小鼠对比剂诱导的血脑屏障损伤的血脑屏障完整性。
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Gut Microbiota and Brain Alterations after Refeeding in a Translational Anorexia Nervosa Rat Model.翻译后文本:厌食症神经症大鼠模型再喂养后肠道菌群和大脑的变化。
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Psychoneuroendocrinology. 2023 Jan;147:105959. doi: 10.1016/j.psyneuen.2022.105959. Epub 2022 Oct 21.
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Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.神经性厌食症急性体重过轻及部分体重恢复个体的脑结构:“ENIGMA饮食失调工作组”的协同分析
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