Fernández Del Campo I S, de la Fuente A J, Díaz I, Plaza I, Merchán M A
Lab.4 Auditory Neuroplasticity, Institute for Neuroscience of Castilla y León, University of Salamanca, Salamanca, Spain.
Brain Struct Funct. 2025 Apr 25;230(4):56. doi: 10.1007/s00429-025-02912-w.
Presbycusis or age-related hearing loss (ARHL) affects millions of people worldwide, increasing their risk of cognitive decline and poor quality of life. However, ARHL remains an irreversible condition due to our inability to induce inner-ear hair cell regeneration. Nevertheless, multisession epidural stimulation of the auditory cortex (AC) at the onset of ARHL prevents hearing threshold elevation in naturally aging Wistar rats. Accordingly, we hypothesized that anodal direct current (DC) stimulation of the AC may also compensate for age-related maladaptive, activity-dependent changes. Here, we examined immunocytochemical markers in the AC, including early genes (c-fos and Arc), AMPA receptors (GluR2/3), parvalbumin (PV), and GAD67, along with auditory-evoked potentials (CAEPs) recorded in both auditory and visual (VC) cortices. When comparing 6 and 18.13-month-old rats without AC simulation, we observed loss of c-fos and Arc-positive neurons and decreased GluR2/3 expression, confirming altered AC neuronal network plasticity and activation. In addition, we noted changes in PV and decreased GAD67 immunoreactivity suggesting disrupted inhibition and significantly increased wave amplitudes in CAEPs, altered AC latencies, and decreased VC responses. By contrast, electrically stimulated rats showed no significant variations in early gene markers, GluR2/3, PV, or GAD67 with age, and the amplitudes and latencies of CAEPs recorded in their AC and VC resembled those of young rat. These findings indicate that anodal DC stimulation at the onset of ARHL delays AC aging by minimizing the loss of inhibition and preventing increases in cortical excitability in Wistar rats.
老年性聋或年龄相关性听力损失（ARHL）影响着全球数百万人，增加了他们认知能力下降和生活质量低下的风险。然而，由于我们无法诱导内耳毛细胞再生，ARHL仍然是一种不可逆的病症。尽管如此，在ARHL开始时对听觉皮层（AC）进行多疗程硬膜外刺激可防止自然衰老的Wistar大鼠听力阈值升高。因此，我们推测对AC进行阳极直流电（DC）刺激也可能补偿与年龄相关的适应性不良、依赖活动的变化。在这里，我们检查了AC中的免疫细胞化学标志物，包括早期基因（c-fos和Arc）、AMPA受体（GluR2/3）、小白蛋白（PV）和GAD67，以及在听觉和视觉（VC）皮层中记录的听觉诱发电位（CAEPs）。在比较未进行AC模拟的6个月和18.13个月大的大鼠时，我们观察到c-fos和Arc阳性神经元的丢失以及GluR2/3表达的降低，证实了AC神经元网络可塑性和激活的改变。此外，我们注意到PV的变化和GAD67免疫反应性的降低，表明抑制作用受到破坏，并且CAEPs中的波幅显著增加、AC潜伏期改变以及VC反应降低。相比之下，电刺激的大鼠在早期基因标志物、GluR2/3、PV或GAD67方面没有随年龄出现显著变化，并且在它们的AC和VC中记录的CAEPs的波幅和潜伏期与年轻大鼠相似。这些发现表明，在ARHL开始时进行阳极DC刺激可通过最小化抑制作用的丧失并防止Wistar大鼠皮层兴奋性增加来延缓AC衰老。
