Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Delhi, India.
Department of Anatomy, All India Institute of Medical Sciences, Delhi, India.
Brain Res Bull. 2019 Apr;147:47-57. doi: 10.1016/j.brainresbull.2019.02.006. Epub 2019 Feb 13.
Hearing loss and cognitive decline are commonly associated with aging and morbidity. Present clinical interest lies in whether peripheral hearing loss promotes cognitive decline and if prophylaxis with selective adenosine receptor agonist CGS21680 effectively mitigates the adverse effects. In the current study, male Sprague Dawley rats weighing 200-250 g m were randomly allocated into three groups: Group 1) rats exposed to 100 dB SPL white noise, 2 h a day for 15 consecutive days, 2) rats supplemented with an adenosine receptor agonist, CGS21680 at 100 μg/kg/day prior to noise exposure and 3) unexposed control rats. Baseline hearing and cognition assessed by auditory brainstem response (ABR) and water maze respectively was undertaken for all the groups. Phalloidin stain and synaptic ribbons count in cochlea, and, Ki67, DCX and NeuN in hippocampus were observed by immunohistochemistry. It was inferred that noise exposed rats showed elevated thresholds of ABR and poorer performances in spatial working memory when compared with controls. On the contrary, CGS21680 administered group exhibited improved ABR and cognitive functions with shorter mean latency and path-length to reach the platform, significant reduction in the noise induced loss of synaptic ribbons count and increased number of Ki67 and doublecortin (DCX) positive cells compared to their noise exposed counterparts. Pharmacologic intervention with selective A receptor agonist CGS21680 provided adequate protection from noise by effectively maintaining hearing threshold levels, cell viability in cochlea and hippocampus & functional/intact reference memory.
听力损失和认知能力下降通常与衰老和发病有关。目前的临床关注点在于外周听力损失是否会促进认知能力下降，以及选择性腺苷受体激动剂 CGS21680 的预防是否能有效减轻不良影响。在目前的研究中，体重为 200-250g 的雄性 Sprague Dawley 大鼠随机分为三组：1）暴露于 100dB SPL 白噪声组，每天 2 小时，连续 15 天；2）在噪声暴露前给予腺苷受体激动剂 CGS21680 100μg/kg/天的补充组；3）未暴露于噪声的对照组。所有组均进行听觉脑干反应（ABR）和水迷宫评估的基线听力和认知测试。用免疫组织化学观察耳蜗中的鬼笔环肽染色和突触带计数，以及海马中的 Ki67、DCX 和 NeuN。推断与对照组相比，暴露于噪声的大鼠的 ABR 阈值升高，空间工作记忆表现更差。相反，给予 CGS21680 的组表现出改善的 ABR 和认知功能，潜伏期和到达平台的路径长度更短，与噪声暴露组相比，突触带计数的噪声诱导损失显著减少，Ki67 和双皮质素（DCX）阳性细胞数量增加。选择性 A 受体激动剂 CGS21680 的药物干预通过有效维持听力阈值水平、耳蜗和海马中的细胞活力以及功能/完整的参考记忆，为听力提供了充分的保护。
