Department of Neuroscience, Division of Auditory Neuroscience, and Cluster of Excellence, Hearing4all, Carl von Ossietzky University, Oldenburg 26129, Germany
Department of Neuroscience, Division of Auditory Neuroscience, and Cluster of Excellence, Hearing4all, Carl von Ossietzky University, Oldenburg 26129, Germany.
eNeuro. 2020 May 8;7(3). doi: 10.1523/ENEURO.0511-19.2020. Print 2020 May/Jun.
Alterations in inhibitory circuits of the primary auditory cortex (pAC) have been shown to be an aspect of aging and age-related hearing loss (AHL). Several studies reported a decline in parvalbumin (PV) immunoreactivity in aged rodent pAC of animals displaying AHL and conclude a relationship between reduced sensitivity and declined PV immunoreactivity. However, it remains elusive whether AHL or a general molecular aging is causative for decreased PV immunoreactivity. In this study, we aimed to disentangle the effects of AHL and general aging on PV immunoreactivity patterns in inhibitory interneurons of mouse pAC. We compared young and old animals of a mouse line with AHL (C57BL/6) and a mutant (C57B6.CAST- ) that is not vulnerable to AHL according to their hearing status by measuring auditory brainstem responses (ABRs) and by an immunohistochemical evaluation of the PV immunoreactivity patterns in two dimensions (rostro-caudal and layer) in the pAC. Although AHL could be confirmed by ABR measurements for the C57BL/6 mice, both aged strains showed a similar reduction of PV positive interneurons in both, number and density. The pattern of reduction across the rostro-caudal axis and across cortical layers was similar for both aged lines. Our results demonstrate that a reduced PV immunoreactivity is a sign of general, molecular aging and not related to AHL.
初级听觉皮层(pAC)抑制回路的改变已被证明是衰老和与年龄相关的听力损失(AHL)的一个方面。几项研究报告称,在表现出 AHL 的老年啮齿动物 pAC 中,钙结合蛋白 1(PV)免疫反应性下降,并得出敏感性降低与 PV 免疫反应性下降之间存在相关性的结论。然而,AHL 或一般分子衰老是否导致 PV 免疫反应性下降仍然难以确定。在这项研究中,我们旨在厘清 AHL 和一般衰老对小鼠 pAC 抑制性中间神经元中 PV 免疫反应性模式的影响。我们通过测量听觉脑干反应(ABR)并通过在 pAC 中进行二维(前后和层)的 PV 免疫反应性模式的免疫组织化学评估,比较了具有 AHL(C57BL/6)和不易受 AHL 影响的突变体(C57B6.CAST- )的年轻和老年动物的听觉状况。尽管 ABL 可以通过 C57BL/6 小鼠的 ABR 测量来证实,但两种老年品系的 PV 阳性中间神经元数量和密度都有类似的减少。两种老年品系在前后轴和皮质层上的减少模式相似。我们的结果表明,PV 免疫反应性降低是一般分子衰老的标志,与 AHL 无关。