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神经丝降解参与了老年大鼠剖腹手术后认知功能障碍的发生。

Neurofilament degradation is involved in laparotomy-induced cognitive dysfunction in aged rats.

机构信息

Department of Anesthesiology, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China.

Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.

出版信息

Aging (Albany NY). 2020 Nov 24;12(24):25643-25657. doi: 10.18632/aging.104172.

DOI:10.18632/aging.104172
PMID:33232265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7803518/
Abstract

Excessive neuroinflammatory responses play important roles in the development of postoperative cognitive dysfunction (POCD). Neurofilaments (NFs) were essential to the structure of axon and nerve conduction; and the abnormal degradation of NFs were always accompanied with degenerative diseases, which were also characterized by excessive neuroinflammatory responses in brain. However, it is still unclear whether the NFs were involved in the POCD. In this study, the LC-MS/MS method was used to explore the neuroinflammatory response and NFs of POCD in aged rats. Moreover, trichostatin A (TSA), an inflammation-related drug, was selected to test whether it could improve the surgery-induced cognitive dysfunction, inflammatory responses and NFs. Evident cognitive dysfunction, excessive microglia activation, neuroinflammatory responses and upregulated NFs in hippocampus were observed in the POCD group. TSA pretreatment could significantly mitigate these changes. The KEGG analysis revealed that nine pathways were enriched in the TSA + surgery group (versus the surgery group). Among them, two signaling pathways were closely related with the changes of NFs proteins. In conclusion, surgery could impair the cognitive function and aggravate neuroinflammation and NFs. The TSA could significantly improve these changes which might be related to the activation of the "focal adhesion" and "ECM-receptor interaction" pathways.

摘要

过度的神经炎症反应在术后认知功能障碍 (POCD) 的发展中起着重要作用。神经丝 (NFs) 对轴突结构和神经传导至关重要；NFs 的异常降解总是伴随着退行性疾病，这些疾病的特征也是大脑中过度的神经炎症反应。然而，NFs 是否参与 POCD 仍不清楚。在这项研究中，使用 LC-MS/MS 方法来探讨老年大鼠 POCD 中的神经炎症反应和 NFs。此外，选择了 Trichostatin A（TSA），一种与炎症相关的药物，来测试它是否可以改善手术引起的认知功能障碍、炎症反应和 NFs。在 POCD 组中观察到明显的认知功能障碍、小胶质细胞过度激活、神经炎症反应和海马 NF 上调。TSA 预处理可显著减轻这些变化。KEGG 分析显示 TSA + 手术组（与手术组相比）中有 9 条通路富集。其中，两条信号通路与 NFs 蛋白的变化密切相关。总之，手术可损害认知功能并加重神经炎症和 NFs。TSA 可显著改善这些变化，这可能与“粘着斑”和“ECM-受体相互作用”途径的激活有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ca/7803518/7f9afdb82887/aging-12-104172-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ca/7803518/0e312d70ddd6/aging-12-104172-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ca/7803518/7f9afdb82887/aging-12-104172-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ca/7803518/aa76153be848/aging-12-104172-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ca/7803518/7da683735cf8/aging-12-104172-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ca/7803518/336c9a6ec22f/aging-12-104172-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ca/7803518/86b7ce9e0f93/aging-12-104172-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ca/7803518/7f9afdb82887/aging-12-104172-g007.jpg

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