Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY, 14214, USA.
Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY, 14214, USA.
Hear Res. 2020 Sep 15;395:108022. doi: 10.1016/j.heares.2020.108022. Epub 2020 Jul 8.
Acoustic information transduced by cochlear hair cells is continuously relayed from the auditory pathway to other sensory, motor, emotional and cognitive centers in the central nervous system. Human epidemiological studies have suggested that hearing loss is a risk factor for dementia and cognitive decline, but the mechanisms contributing to these memory and cognitive impairments are poorly understood. To explore these issues in a controlled experimental setting, we exposed adult rats to a series of intense blast wave exposures that significantly reduced the neural output of the cochlea. Several weeks later, we used the Morris Water Maze test, a hippocampal-dependent memory task, to assess the ability of Blast Wave and Control rats to learn a spatial navigation task (memory acquisition) and to remember what they had learned (spatial memory retention) several weeks earlier. The elevated plus maze and open field arena were used to test for anxiety-like behaviors. Afterwards, hippocampal cell proliferation and neurogenesis were evaluated using bromodeoxyuridine (BrdU), doublecortin (DCX), and Neuronal Nuclei (NeuN) immunolabeling. The Blast Wave and Control rats learned the spatial navigation task equally well and showed no differences on tests of anxiety. However, the Blast Wave rats performed significantly worse on the spatial memory retention task, i.e., remembering where they had been two weeks earlier. Deficits on the spatial memory retention task were associated with significant decreases in hippocampal cell proliferation and neurogenesis. Our blast wave results are consistent with other experimental manipulations that link spatial memory retention deficits (long term memory) with decreased cell proliferation and neurogenesis in the hippocampus. These results add to the growing body of knowledge linking blast-induced cochlear hearing loss with the cognitive deficits often seen in combat personnel and provide mechanistic insights into these extra auditory disorders that could lead to therapeutic interventions.
耳蜗毛细胞转导的声信息不断从听觉通路中继到中枢神经系统的其他感觉、运动、情感和认知中心。人类流行病学研究表明，听力损失是痴呆和认知能力下降的一个危险因素，但导致这些记忆和认知障碍的机制尚不清楚。为了在受控的实验环境中探讨这些问题，我们使成年大鼠暴露于一系列强烈的爆炸波中，这些爆炸波显著降低了耳蜗的神经输出。几周后，我们使用 Morris 水迷宫测试，一种海马依赖的记忆任务，来评估 Blast Wave 和 Control 大鼠学习空间导航任务（记忆获取）的能力，以及在数周前记住所学内容（空间记忆保留）的能力。高架十字迷宫和开阔场竞技场用于测试焦虑样行为。之后，使用溴脱氧尿苷（BrdU）、双皮质素（DCX）和神经元核（NeuN）免疫标记评估海马细胞增殖和神经发生。Blast Wave 和 Control 大鼠同样很好地学习了空间导航任务，在焦虑测试中没有差异。然而，Blast Wave 大鼠在空间记忆保留任务中的表现明显较差，即，无法记住两周前的位置。空间记忆保留任务的缺陷与海马细胞增殖和神经发生的显著减少有关。我们的爆炸波结果与其他实验操作一致，这些操作将空间记忆保留缺陷（长期记忆）与海马中的细胞增殖和神经发生减少联系起来。这些结果增加了与爆炸引起的耳蜗听力损失与战斗人员中经常出现的认知缺陷相关的知识体系，并为这些额外的听觉障碍提供了机制上的见解，这些障碍可能导致治疗干预。
