Age-Dependent Auditory Processing Deficits after Cochlear Synaptopathy Depend on Auditory Nerve Latency and the Ability of the Brain to Recruit LTP/BDNF.
Age-Dependent Auditory Processing Deficits after Cochlear Synaptopathy Depend on Auditory Nerve Latency and the Ability of the Brain to Recruit LTP/BDNF.
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DOI：
10.3390/brainsci10100710
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发表时间：
2020-10-06
期刊：
影响因子：
3.3
通讯作者：
Singer W
中科院分区：
文献类型：
--
作者：
Marchetta P;Savitska D;Kübler A;Asola G;Manthey M;Möhrle D;Schimmang T;Rüttiger L;Knipper M;Singer W
听觉神经纤维与毛细胞的分离（耳蜗突触病）与时间处理缺陷和言语识别能力受损有关。两者之间的联系是难以捉摸的。我们以前已经证明，耳蜗突触病，如果通过增强的输入/输出功能（神经增益）集中补偿，可以防止年龄依赖性的时间辨别力丧失。研究还发现，声损伤后的中枢神经增益与海马长时程增强（LTP）和脑源性神经营养因子（BDNF）的上调有关。使用中年和老年BDNF活外显子可视化（BLEV）报告小鼠，我们分析了特定的招聘LTP和活动依赖性使用的BDNF外显子IV和VI启动子相对于耳蜗突触病和中央（颞叶）处理。对于这两个群体，标本具有较高或较低的能力，中央补偿减少听觉神经activity. Statistically，低补偿小鼠组不同，从高补偿延长听觉神经潜伏期。此外，低补偿器表现出衰减的幅度调制音的反应，并减少海马LTP和BDNF转录水平相比，高补偿器。这些结果表明，听觉神经处理的潜伏期，海马LTP的招聘，和BDNF转录，是年龄依赖性听觉处理缺陷的关键因素，而不是耳蜗突触病或老化本身。
Age-related decoupling of auditory nerve fibers from hair cells (cochlear synaptopathy) has been linked to temporal processing deficits and impaired speech recognition performance. The link between both is elusive. We have previously demonstrated that cochlear synaptopathy, if centrally compensated through enhanced input/output function (neural gain), can prevent age-dependent temporal discrimination loss. It was also found that central neural gain after acoustic trauma was linked to hippocampal long-term potentiation (LTP) and upregulation of brain-derived neurotrophic factor (BDNF). Using middle-aged and old BDNF-live-exon-visualization (BLEV) reporter mice we analyzed the specific recruitment of LTP and the activity-dependent usage of Bdnf exon-IV and -VI promoters relative to cochlear synaptopathy and central (temporal) processing. For both groups, specimens with higher or lower ability to centrally compensate diminished auditory nerve activity were found. Strikingly, low compensating mouse groups differed from high compensators by prolonged auditory nerve latency. Moreover, low compensators exhibited attenuated responses to amplitude-modulated tones, and a reduction of hippocampal LTP and Bdnf transcript levels in comparison to high compensators. These results suggest that latency of auditory nerve processing, recruitment of hippocampal LTP, and Bdnf transcription, are key factors for age-dependent auditory processing deficits, rather than cochlear synaptopathy or aging per se.
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影响因子：
3
作者：
Bharadwaj HM;Verhulst S;Shaheen L;Liberman MC;Shinn-Cunningham BG
通讯作者：
Shinn-Cunningham BG
影响因子：
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