Katchur Nicole J, Notterman Daniel A
Department of Molecular Biology, Princeton University, Princeton, NJ, United States.
Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, United States.
Front Neurol. 2024 Mar 19;15:1378620. doi: 10.3389/fneur.2024.1378620. eCollection 2024.
Traumatic brain injury (TBI) is a major global health concern and is increasingly recognized as a risk factor for neurodegenerative diseases including Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Repetitive TBIs (rTBIs), commonly observed in contact sports, military service, and intimate partner violence (IPV), pose a significant risk for long-term sequelae. To study the long-term consequences of TBI and rTBI, researchers have typically used mammalian models to recapitulate brain injury and neurodegenerative phenotypes. However, there are several limitations to these models, including: (1) lengthy observation periods, (2) high cost, (3) difficult genetic manipulations, and (4) ethical concerns regarding prolonged and repeated injury of a large number of mammals. Aquatic vertebrate model organisms, including (sea lampreys), zebrafish (), (), and (), are emerging as valuable tools for investigating the mechanisms of rTBI and tauopathy. These non-mammalian models offer unique advantages, including genetic tractability, simpler nervous systems, cost-effectiveness, and quick discovery-based approaches and high-throughput screens for therapeutics, which facilitate the study of rTBI-induced neurodegeneration and tau-related pathology. Here, we explore the use of non-vertebrate and aquatic vertebrate models to study TBI and neurodegeneration. , in particular, provides an opportunity to explore the longitudinal effects of mild rTBI and its impact on endogenous tau, thereby offering valuable insights into the complex interplay between rTBI, tauopathy, and neurodegeneration. These models provide a platform for mechanistic studies and therapeutic interventions, ultimately advancing our understanding of the long-term consequences associated with rTBI and potential avenues for intervention.
创伤性脑损伤（TBI）是一个重大的全球健康问题，并且越来越被认为是包括阿尔茨海默病（AD）和慢性创伤性脑病（CTE）在内的神经退行性疾病的一个风险因素。重复性创伤性脑损伤（rTBI）常见于接触性运动、军事服役和亲密伴侣暴力（IPV）中，会带来长期后遗症的重大风险。为了研究TBI和rTBI的长期后果，研究人员通常使用哺乳动物模型来重现脑损伤和神经退行性表型。然而，这些模型存在若干局限性，包括：（1）观察期长，（2）成本高，（3）基因操作困难，以及（4）对大量哺乳动物进行长期和反复损伤所涉及的伦理问题。包括七鳃鳗（海七鳃鳗）、斑马鱼（斑马鱼）、非洲爪蟾（非洲爪蟾）和非洲青鳉（青鳉）在内的水生脊椎动物模型正成为研究rTBI和tau蛋白病机制的有价值工具。这些非哺乳动物模型具有独特的优势，包括遗传易处理性、更简单的神经系统、成本效益、基于快速发现的方法以及用于治疗学的高通量筛选，这有助于研究rTBI诱导的神经退行性变和tau相关病理。在这里，我们探讨使用非脊椎动物和水生脊椎动物模型来研究TBI和神经退行性变。特别是青鳉，它提供了一个机会来探索轻度rTBI的纵向影响及其对内源性tau的影响，从而为rTBI、tau蛋白病和神经退行性变之间的复杂相互作用提供有价值的见解。这些模型为机制研究和治疗干预提供了一个平台，最终增进我们对与rTBI相关的长期后果以及潜在干预途径的理解。
