在D-半乳糖模拟衰老模型中，中枢听觉功能衰退先于耳蜗缺陷出现。

文献信息

中文摘要

年龄相关性听力损失反映了外周耳蜗和中枢听觉通路同时发生的退行性改变。由于二者随自然衰老共同衰退，区分其相对贡献一直具有挑战性。本研究检验以下假说：全身性给予D-半乳糖（D-gal）会选择性地加速中枢听觉衰老，同时保留外周耳蜗功能。八只雄性Fischer 344大鼠连续八周每日接受皮下注射D-gal（500 mg/kg）。在两个通道记录听觉诱发电位，包括听性脑干反应（ABR）和包络跟随反应（EFR），时间点有三个：注射前、注射刚结束时（注射后2个月）以及停止注射后12个月。注射后2个月，来自中枢听觉发生器的ABR波幅（IV波和V波）以及对慢调制频率（≤45 Hz）的EFR显著降低，后者反映中脑和皮层发生器。相比之下，此时ABR阈值、来自外周发生器的波幅（I波和III波）以及对快调制速率（>128 Hz）的EFR（反映外周神经活动）均保持不变，表明耳蜗和早期脑干功能得以保留。外周缺陷仅在12个月随访时才出现，表现为阈值升高、外周波幅降低以及快调制速率下的EFR降低，与老年性聋一致。这些发现表明存在明确的时间分离：在D-gal模型中，中枢听觉衰退先于年龄相关的外周耳蜗和神经损失。该范式提供了一个可操作的实验窗口，可在与年龄相关耳蜗病理分离的情况下研究中枢听觉衰老机制，从而弥合老年性聋外周模型与中枢模型之间的重要空白。

英文摘要

Age-related hearing loss reflects a mixture of concurrent peripheral cochlear and central auditory pathway degeneration. Disentangling their relative contributions has remained challenging because both decline together with natural aging. Here, we test the hypothesis that systemic D-galactose (D-gal) administration will selectively accelerate central auditory aging while preserving peripheral cochlear function. Eight male Fischer 344 rats received daily subcutaneous D-gal injections (500 mg/kg) for eight consecutive weeks. Two-channel auditory evoked potentials, including auditory brainstem responses (ABRs) and envelope-following responses (EFRs), were recorded at three time points: pre-injection, immediately following injections (2 months post), and 12 months post-injection cessation. Two months post-injection, there was a significant reduction in ABR wave amplitudes from central auditory generators (Waves IV and V) and EFRs to slow modulation frequencies (≤45 Hz), which reflect midbrain and cortical generators. In contrast, ABR thresholds, wave amplitudes from peripheral generators (Waves I and III), and EFRs to fast modulation rates (>128 Hz), reflecting peripheral neural activity, remained unchanged at this time point, indicating preserved cochlear and early brainstem function. Peripheral deficits emerged only by the 12-month follow-up, with elevated thresholds, reduced peripheral wave amplitudes, and reduced EFRs at fast modulation rates, consistent with presbycusis. These findings demonstrate a clear temporal dissociation in which central auditory decline in the D-gal model precedes age-related peripheral cochlear and neural loss. This paradigm provides a tractable experimental window for studying mechanisms of central auditory aging in isolation from age-related cochlear pathology, bridging an important gap between peripheral and central models of presbycusis.