Lymphatic dysfunction correlates with inflammation in a mouse model of amyotrophic lateral sclerosis.

IF 3.3 3区 医学 Q2 CELL BIOLOGY
Disease Models & Mechanisms Pub Date : 2025-07-01 Epub Date: 2025-07-16 DOI:10.1242/dmm.052148
Akshaya Narayanan, Bonnie L Seaberg, Andrew Buxton, Alexandra Vernino, Victoria E Williams, Anthony Matarazzo, Jeet Kekre, Bhuvaneshwaran Subramanian, Wei Wang, Joseph M Rutkowski, Michelle Hook, Dylan A McCreedy, Mariappan Muthuchamy, Mendell Rimer
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引用次数: 0

Abstract

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, ultimately fatal neurodegenerative disease, without effective modifying treatments. It affects both lower and upper motor neurons, causing skeletal muscle denervation and paralysis. Regardless of the mechanisms that initiate and drive ALS, chronic neuroinflammation and systemic immune system activation play key roles in disease progression. The lymphatic system is a network of vessels and organs essential for immune surveillance, tissue fluid balance and lipid absorption, critical for the resolution and progression of inflammation in the periphery. Its recent rediscovery in the central nervous system raises the possibility of it playing similar roles in neurological and neurodegenerative diseases featuring prominent neuroinflammation, such as ALS. We hypothesized that the structure and function of lymphatics are compromised in the most widely used murine model of ALS, the SOD1-G93A mouse. We found that these mice exhibit lymph transport dysfunction, diminished intrinsic lymphatic vessel tonic and phasic contractions, and an association between inflammation and lymphatic marker upregulation, despite absence of major structural changes in lymphatic network coverage in key affected tissues in the disease, skeletal muscle and spinal cord.

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SOD1-G93A肌萎缩性侧索硬化症小鼠模型淋巴功能障碍与炎症相关。
肌萎缩性侧索硬化症(ALS)是一种快速进展,最终致命的神经退行性疾病,没有有效的治疗方法。它影响上下运动神经元,引起骨骼肌失神经支配和瘫痪。无论启动和驱动ALS的机制如何,慢性神经炎症和全身免疫系统激活在疾病进展中起着关键作用。淋巴系统是一个由血管和器官组成的网络,对免疫监视、组织液平衡和脂质吸收至关重要,对周围炎症的消退和进展至关重要。它最近在中枢神经系统中的重新发现,提出了它在神经和神经退行性疾病中发挥类似作用的可能性,这些疾病以突出的神经炎症为特征,如ALS。我们假设在最广泛使用的ALS小鼠模型SOD1-G93A小鼠中淋巴的结构和功能受到损害。我们发现这些小鼠表现出淋巴运输功能障碍,固有淋巴管强直和阶段性收缩减弱,炎症和淋巴标记物上调之间存在关联,尽管在疾病的关键受影响组织,骨骼肌和脊髓中淋巴网络覆盖没有主要的结构变化。
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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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