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终点小鼠模型中的表型、行为和全身特征。

Phenotypical, Behavioral, and Systemic Hallmarks in End-Point Mouse Scenarios.

作者信息

Castillo-Mariqueo Lidia, Alveal-Mellado Daniel, Giménez-Llort Lydia

机构信息

Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain.

Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193 Barcelona, Spain.

出版信息

Animals (Basel). 2025 Feb 12;15(4):521. doi: 10.3390/ani15040521.

DOI:10.3390/ani15040521
PMID:40003003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11851987/
Abstract

The state of frailty is a clinical-biological syndrome that affects the older population with a higher risk of functional dependence. Animal models can provide a tool to study this complex scenario. In the present work, we analyzed the physical and behavioral hallmarks of end-point status in 16-month-old mice (C57BL/6J) according to animal welfare regulations compared to age-matched counterparts with normal aging. A group of 6-month-old mice was added to control for age bias. First, we identified 'structural kyphosis' (visible and unmodifiable deformation in locomotion) correlated with piloerection as the hallmarks of the physical frailty phenotype compared to the 'postural kyphosis' (adjustment to counteract increased visceral volume but attenuated during locomotion) of old mice with normal aging. Alopecia (barbering) was presented in both old groups. Normal levels of exploratory activity in the corner test for neophobia and triceps surae muscle weight but an increased latency of rearing indicated the poorest emotional phenotype, with a possible contribution of structural kyphosis. The presence of hepatomegaly and splenomegaly counteracted the significant WAT loss commonly associated with end-of-life traits, which should have a normal body weight but preserved muscle mass.

摘要

衰弱状态是一种临床生物学综合征,影响老年人群,使其功能依赖风险更高。动物模型可为研究这一复杂情况提供工具。在本研究中,根据动物福利规定,我们分析了16月龄小鼠(C57BL/6J)与年龄匹配的正常衰老对照小鼠相比,终点状态的身体和行为特征。添加了一组6月龄小鼠以控制年龄偏差。首先,我们确定与竖毛相关的“结构性脊柱后凸”(运动中可见且不可改变的变形)是身体衰弱表型的特征,而正常衰老的老年小鼠的“姿势性脊柱后凸”(为抵消内脏体积增加而进行的调整,但在运动中减弱)则不是。两组老年小鼠均出现脱毛(拔毛)现象。在新物体恐惧的角落试验中探索活动水平正常,腓肠肌重量正常,但站立潜伏期增加表明情绪表型最差,结构性脊柱后凸可能起了作用。肝肿大和脾肿大的存在抵消了通常与生命末期特征相关的显著白色脂肪组织损失,这些小鼠体重应正常但肌肉质量得以保留。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d53/11851987/1e918570d549/animals-15-00521-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d53/11851987/b9d22d408ebb/animals-15-00521-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d53/11851987/81493df8ec53/animals-15-00521-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d53/11851987/1e918570d549/animals-15-00521-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d53/11851987/b9d22d408ebb/animals-15-00521-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d53/11851987/81493df8ec53/animals-15-00521-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d53/11851987/1e918570d549/animals-15-00521-g003.jpg

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本文引用的文献

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Glomerular Hypertrophy and Splenic Red Pulp Degeneration Concurrent with Oxidative Stress in 3xTg-AD Mice Model for Alzheimer's Disease and Its Exacerbation with Sex and Social Isolation.阿尔茨海默病 3xTg-AD 小鼠模型中氧化应激时肾小球肥大和脾红髓变性及其加剧与性别和社会隔离的关系。
Int J Mol Sci. 2024 Jun 1;25(11):6112. doi: 10.3390/ijms25116112.
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Hepatic Oxi-Inflammation and Neophobia as Potential Liver-Brain Axis Targets for Alzheimer's Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity.肝氧化-炎症和新恐惧症作为阿尔茨海默病和衰老的潜在肝脑轴靶点,对性别、隔离和肥胖具有高度敏感性。
Cells. 2023 May 30;12(11):1517. doi: 10.3390/cells12111517.
3
Translational Modeling of Psychomotor Function in Normal and AD-Pathological Aging With Special Concerns on the Effects of Social Isolation.
正常及阿尔茨海默病病理衰老中精神运动功能的转化模型:特别关注社会隔离的影响
Front Aging. 2021 Mar 19;2:648567. doi: 10.3389/fragi.2021.648567. eCollection 2021.
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Modeling Functional Limitations, Gait Impairments, and Muscle Pathology in Alzheimer's Disease: Studies in the 3xTg-AD Mice.阿尔茨海默病中功能限制、步态障碍和肌肉病理学建模:3xTg-AD小鼠研究
Biomedicines. 2021 Oct 1;9(10):1365. doi: 10.3390/biomedicines9101365.
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Kyphosis and bizarre patterns impair spontaneous gait performance in end-of-life mice with Alzheimer's disease pathology while gait is preserved in normal aging.在阿尔茨海默病病理的生命末期小鼠中,后凸和奇异模式会损害自发步态表现,而在正常衰老中步态则得以保留。
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Digging Signatures in 13-Month-Old 3xTg-AD Mice for Alzheimer's Disease and Its Disruption by Isolation Despite Social Life Since They Were Born.挖掘13月龄3xTg-AD小鼠中阿尔茨海默病的特征及其自出生以来虽有社交生活但被隔离所破坏的情况。
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