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在老年APP/PS1小鼠中,海马体效应免疫细胞浸润增加,同时脑室体积扩大。

Heightened effector immune cell infiltration of the hippocampus concurrently with brain ventricular volume expansion in aged APP/PS1 mice.

作者信息

Maynes Mark A, Owens Carley A, Anani-Wolf Delaney M, Tritz Zachariah P, Jin Fang, Hansen Michael J, Seady Marina, Johnson Aaron J

机构信息

Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA.

Department of Immunology, Mayo Clinic, Rochester, MN, USA.

出版信息

J Neuroimmunol. 2025 Sep 15;406:578646. doi: 10.1016/j.jneuroim.2025.578646. Epub 2025 May 26.

DOI:10.1016/j.jneuroim.2025.578646
PMID:40449343
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12286741/
Abstract

Alzheimer's disease (AD) is the most common form of dementia for which the role of neuroinflammation is becoming more realized. Recent studies have shown that immune cells infiltrate the hippocampus and the cortex of AD patients as well as mouse models of the disease. In this study, we employed T2-weighted magnetic resonance imaging (MRI) to view changes in ventricular volume in addition to spectral flow cytometric assessment of the hippocampus infiltrating immune profile in the aged APP/PS1 mice. Aged APP/PS1 mice present with increased size of lateral, dorsal, and ventral ventricles plus increased numbers of hippocampus infiltrating effector immune cell subsets, including CD8 T cells expressing IFNγ, granzyme B, and perforin along with other cell types such as γδ T cells, neutrophils, and NK cells. The concurrent increase in effector cell types with ventricular enlargement expands the putative mechanism of brain atrophy in the APP/PS1 mouse model to include cytolytic functions of these aforementioned immune cell subsets.

摘要

阿尔茨海默病(AD)是最常见的痴呆形式,神经炎症在其中的作用正日益受到重视。最近的研究表明,免疫细胞会浸润AD患者以及该疾病小鼠模型的海马体和皮质。在本研究中,我们采用T2加权磁共振成像(MRI)来观察脑室容积的变化,并通过光谱流式细胞术评估老年APP/PS1小鼠海马体浸润免疫谱。老年APP/PS1小鼠的侧脑室、背侧脑室和腹侧脑室增大,海马体浸润效应免疫细胞亚群数量增加,包括表达IFNγ、颗粒酶B和穿孔素的CD8 T细胞以及其他细胞类型,如γδ T细胞、中性粒细胞和NK细胞。效应细胞类型与脑室扩大同时增加,将APP/PS1小鼠模型中脑萎缩的假定机制扩展到包括上述免疫细胞亚群的细胞溶解功能。

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本文引用的文献

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Brain resident memory T cells rapidly expand and initiate neuroinflammatory responses following CNS viral infection.脑内驻留记忆 T 细胞在中枢神经系统病毒感染后迅速扩增并引发神经炎症反应。
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Immune cell counts in cerebrospinal fluid predict cognitive function in aging and neurodegenerative disease.脑脊液中的免疫细胞计数可预测衰老和神经退行性疾病中的认知功能。
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Inhibition of Perforin-Mediated Neurotoxicity Attenuates Neurological Deficits After Ischemic Stroke.抑制穿孔素介导的神经毒性可减轻缺血性中风后的神经功能缺损。
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