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High-frequency head impact causes chronic synaptic adaptation and long-term cognitive impairment in mice
Nature Communications ( IF 16.6 ) Pub Date : 2021-05-10 , DOI: 10.1038/s41467-021-22744-6
Stephanie S Sloley 1, 2 , Bevan S Main 2 , Charisse N Winston 1, 2 , Alex C Harvey 2 , Alice Kaganovich 3 , Holly T Korthas 1, 2 , Adam P Caccavano 1, 4 , David N Zapple 2 , Jian-Young Wu 1, 2 , John G Partridge 1, 4 , Mark R Cookson 3 , Stefano Vicini 1, 4 , Mark P Burns 1, 2
Affiliation  

Repeated head impact exposure can cause memory and behavioral impairments. Here, we report that exposure to non-damaging, but high frequency, head impacts can alter brain function in mice through synaptic adaptation. High frequency head impact mice develop chronic cognitive impairments in the absence of traditional brain trauma pathology, and transcriptomic profiling of mouse and human chronic traumatic encephalopathy brain reveal that synapses are strongly affected by head impact. Electrophysiological analysis shows that high frequency head impacts cause chronic modification of the AMPA/NMDA ratio in neurons that underlie the changes to cognition. To demonstrate that synaptic adaptation is caused by head impact-induced glutamate release, we pretreated mice with memantine prior to head impact. Memantine prevents the development of the key transcriptomic and electrophysiological signatures of high frequency head impact, and averts cognitive dysfunction. These data reveal synapses as a target of high frequency head impact in human and mouse brain, and that this physiological adaptation in response to head impact is sufficient to induce chronic cognitive impairment in mice.



中文翻译:

高频头部撞击导致小鼠慢性突触适应和长期认知障碍

反复的头部撞击会导致记忆和行为障碍。在这里,我们报告说,暴露于非破坏性但高频的头部撞击可以通过突触适应改变小鼠的大脑功能。在没有传统脑外伤病理学的情况下,高频头部撞击小鼠会出现慢性认知障碍,小鼠和人类慢性创伤性脑病大脑的转录组学分析表明,突触受到头部撞击的强烈影响。电生理分析表明,高频头部撞击会导致神经元中 AMPA/NMDA 比率的慢性改变,这是认知变化的基础。为了证明突触适应是由头部撞击诱导的谷氨酸释放引起的,我们在头部撞击前用美金刚对小鼠进行预处理。美金刚可防止高频头部撞击的关键转录组学和电生理学特征的发展,并避免认知功能障碍。这些数据表明突触是人类和小鼠大脑中高频头部撞击的目标,并且这种对头部撞击的生理适应足以诱发小鼠的慢性认知障碍。

更新日期:2021-05-10
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