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鱼类内耳和侧线的年龄相关性变化。

Age-related changes in the zebrafish and killifish inner ear and lateral line.

机构信息

College of Arts and Sciences, Washington State University Vancouver, Vancouver, WA, 98686, USA.

Department of Integrative Physiology and Neuroscience, Washington State University Vancouver, Vancouver, WA, 98686, USA.

出版信息

Sci Rep. 2024 Mar 20;14(1):6670. doi: 10.1038/s41598-024-57182-z.

Abstract

Age-related hearing loss (ARHL) is a debilitating disorder for millions worldwide. While there are multiple underlying causes of ARHL, one common factor is loss of sensory hair cells. In mammals, new hair cells are not produced postnatally and do not regenerate after damage, leading to permanent hearing impairment. By contrast, fish produce hair cells throughout life and robustly regenerate these cells after toxic insult. Despite these regenerative abilities, zebrafish show features of ARHL. Here, we show that aged zebrafish of both sexes exhibited significant hair cell loss and decreased cell proliferation in all inner ear epithelia (saccule, lagena, utricle). Ears from aged zebrafish had increased expression of pro-inflammatory genes and significantly more macrophages than ears from young adult animals. Aged zebrafish also had fewer lateral line hair cells and less cell proliferation than young animals, although lateral line hair cells still robustly regenerated following damage. Unlike zebrafish, African turquoise killifish (an emerging aging model) only showed hair cell loss in the saccule of aged males, but both sexes exhibit age-related changes in the lateral line. Our work demonstrates that zebrafish exhibit key features of auditory aging, including hair cell loss and increased inflammation. Further, our finding that aged zebrafish have fewer lateral line hair cells yet retain regenerative capacity, suggests a decoupling of homeostatic hair cell addition from regeneration following acute trauma. Finally, zebrafish and killifish show species-specific strategies for lateral line homeostasis that may inform further comparative research on aging in mechanosensory systems.

摘要

年龄相关性听力损失(ARHL)是全球数百万人的一种致残性疾病。虽然 ARHL 有多种潜在原因,但一个共同的因素是感觉毛细胞的丧失。在哺乳动物中,出生后不会产生新的毛细胞,并且在受损后不会再生,导致永久性听力损伤。相比之下,鱼类一生中都会产生毛细胞,并在受到毒性损伤后强烈再生这些细胞。尽管具有这些再生能力,但斑马鱼仍表现出 ARHL 的特征。在这里,我们表明,雌雄两性的老年斑马鱼都表现出内耳上皮(球囊、听小骨、椭圆囊)中明显的毛细胞丧失和细胞增殖减少。与年轻成年动物相比,老年斑马鱼的耳朵中促炎基因的表达增加,巨噬细胞明显更多。老年斑马鱼的侧线毛细胞也比年轻动物少,细胞增殖也少,尽管侧线毛细胞在受到损伤后仍能强烈再生。与斑马鱼不同,非洲蓝珍珠脂鱼(一种新兴的衰老模型)仅在雄性老年鱼的球囊中表现出毛细胞丧失,但两性都表现出侧线的年龄相关变化。我们的工作表明,斑马鱼表现出听觉衰老的关键特征,包括毛细胞丧失和炎症增加。此外,我们发现老年斑马鱼的侧线毛细胞较少,但仍保留再生能力,这表明在急性创伤后,毛细胞的稳态添加与再生之间存在解耦。最后,斑马鱼和脂鱼表现出侧线稳态的物种特异性策略,这可能为机械感觉系统衰老的进一步比较研究提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cca/10954678/bab6c0e5c0ff/41598_2024_57182_Fig1_HTML.jpg

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