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耳蜗背核中的梭形细胞会随着年龄改变其内在电生理特性并在形态上重塑其基底树突。

Fusiform Cells in the Dorsal Cochlear Nucleus Change Intrinsic Electrophysiological Properties and Morphologically Remodel Their Basal Dendrites with Age.

作者信息

Edwards Reginald J, Kasten Michael R, Hutson Kendall A, Lutz Malcolm P, Manis Paul B

机构信息

Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina, United States.

Department of Otolaryngology-Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina, United States.

出版信息

bioRxiv. 2025 Jul 21:2025.07.16.665173. doi: 10.1101/2025.07.16.665173.

Abstract

Age-related hearing loss (ARHL) is the most common cause of sensorineural hearing loss. The cochlear nucleus, the first central auditory structure to receive input from the cochlea, has been shown to be disrupted by ARHL. Fusiform cells (FC), the principal output cell of the dorsal part of the cochlear nucleus (DCN), mature physiologically during hearing onset. Specifically, FCs increase in rate of action potential (AP) rise and decay, stabilizing by postnatal day 14 (P14) in mice. However, whether FC intrinsic electrophysiological properties and morphological characteristics continue to change throughout the life of mice, and how they change due to ARHL, is unknown. We characterized electrophysiological and morphological properties of FCs from CBA/CaJ mice at five stages of age: preweaning (P15-20), pubescent (P21-49), young adult (P50-179), mature adult (P180-364), and old adult (P550-578). Our old adult mice had smaller auditory brainstem evoked response amplitudes and loss of some hair cells, indicative of ARHL onset. We observed no change in FC membrane properties with age. FCs from the old adult group had elevated firing rates, faster repolarization rates, and shorter AP half-widths. Morphologically, there was no change in FC soma shape or size. However, a significant decrease in basal dendritic arborization occurred between preweaning and pubescent ages, followed by an increase in our old adult group, suggesting age-dependent remodeling of the basal dendritic tree at the onset of ARHL. Together, these results suggest that FC physiology and morphology are relatively stable post weaning and become altered during the onset of ARHL.

摘要

年龄相关性听力损失(ARHL)是感音神经性听力损失最常见的原因。耳蜗核是第一个接收来自耳蜗输入的中枢听觉结构,已被证明会因ARHL而受到破坏。梭形细胞(FC)是耳蜗核背侧部分(DCN)的主要输出细胞,在听力开始时生理上成熟。具体而言,FC的动作电位(AP)上升和衰减速率增加,在小鼠出生后第14天(P14)稳定下来。然而,FC的内在电生理特性和形态特征在小鼠的整个生命过程中是否会继续变化,以及它们如何因ARHL而变化,尚不清楚。我们在五个年龄阶段对CBA/CaJ小鼠的FC的电生理和形态特性进行了表征:断奶前(P15 - 20)、青春期(P21 - 49)、年轻成年期(P50 - 179)、成熟成年期(P180 - 364)和老年成年期(P550 - 578)。我们的老年成年小鼠听觉脑干诱发电位幅度较小,且一些毛细胞丢失,表明ARHL开始。我们观察到FC膜特性随年龄没有变化。老年成年组的FC放电率升高、复极化速率更快且AP半宽度更短。在形态上,FC的胞体形状或大小没有变化。然而,断奶前和青春期之间基底树突分支显著减少,随后在我们的老年成年组中增加,这表明在ARHL开始时基底树突存在年龄依赖性重塑。总之,这些结果表明,FC生理和形态在断奶后相对稳定,并在ARHL开始时发生改变。

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