Motor, Cognitive, and Behavioral Impairment in TLR3 and TLR9 Deficient Male Mice: Insights into the Non-Immunological Roles of Toll-Like Receptors

IF 4.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Archives of Medical Research Pub Date : 2024-03-22 DOI:10.1016/j.arcmed.2024.102985
Héctor Vargas-Calderón , Emmanuel Ortega-Robles , Luisa Rocha , Philipp Yu , Oscar Arias-Carrión
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Abstract

Background

Toll-like receptors (TLRs) play a critical role in initiating the innate immune response to infection or injury. Recent studies have uncovered their intriguing functions as moonlighting proteins involved in various biological processes, including development, learning, and memory. However, the specific functions of individual TLRs are still largely unknown.

Aims

We investigated the effects of TLR3 and TLR9 receptor deficiency on motor, cognitive, and behavioral functions during development using genetically modified male mice of different ages.

Methods

We evaluated the motor coordination, anxiety-like behavior, spatial learning, and working memory of male mice lacking the TLR3 and TLR9 genes at different ages (two, four, six, and eight months) using the rotarod, open field, water maze, and T-maze tests.

Results

We observed that the deletion of either TLR3 or TLR9 resulted in impaired motor performance. Furthermore, young TLR3-deficient mice exhibited reduced anxiety-like behavior and spatial learning deficits; however, their working memory was unaffected. In contrast, young TLR9-knockout mice showed hyperactivity and a tendency toward decreased working memory.

Conclusions

These findings provide valuable insights into the broader roles of the TLR system beyond the innate immune response, revealing its involvement in pathways associated with the central nervous system. Importantly, our results establish a strong association between the endosomal receptors TLR3 and TLR9 and the performance of motor, cognitive, and behavioral tasks that change over time. This study contributes to the growing body of research on the multifaceted functions of TLRs and enhances our understanding of their participation in non-immune-related processes.

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TLR3和TLR9缺陷雄性小鼠的运动、认知和行为障碍:对Toll-Like受体非免疫学作用的见解
背景类托尔受体(TLRs)在启动对感染或损伤的先天性免疫反应中起着至关重要的作用。最近的研究揭示了它们作为月光蛋白参与发育、学习和记忆等各种生物过程的有趣功能。目的我们利用不同年龄的转基因雄性小鼠研究了 TLR3 和 TLR9 受体缺乏对发育过程中运动、认知和行为功能的影响。结果我们发现,TLR3 或 TLR9 基因缺失会导致小鼠运动能力受损。此外,TLR3缺失的幼鼠表现出焦虑样行为减少和空间学习障碍,但它们的工作记忆不受影响。与此相反,TLR9 基因敲除的年轻小鼠表现出多动和工作记忆减退的趋势。 结论:这些发现为了解 TLR 系统在先天性免疫反应之外的更广泛作用提供了宝贵的见解,揭示了它参与中枢神经系统相关途径的情况。重要的是,我们的研究结果确定了内体受体 TLR3 和 TLR9 与运动、认知和行为任务表现之间的密切联系,而且这种联系会随着时间的推移而发生变化。这项研究为有关 TLRs 多方面功能的日益增多的研究做出了贡献,并加深了我们对 TLRs 参与非免疫相关过程的理解。
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来源期刊
Archives of Medical Research
Archives of Medical Research 医学-医学:研究与实验
CiteScore
12.50
自引率
0.00%
发文量
84
审稿时长
28 days
期刊介绍: Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.
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