TLR2 deficiency attenuated chronic intermittent hypoxia-induced neurocognitive deficits
TLR2 deficiency attenuated chronic intermittent hypoxia-induced neurocognitive deficits
复制标题
TLR2 缺乏可减轻慢性间歇性缺氧引起的神经认知缺陷
DOI：
10.1016/j.intimp.2020.106284
复制
发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Han, Fang
中科院分区：
文献类型：
--
作者：
Li, Wanting;Yu, Yan;Han, Fang
慢性间歇性缺氧（CIH）是阻塞性睡眠呼吸暂停综合征（OSAS）的主要症状，并通过神经炎症引起神经损伤和认知功能障碍。Toll样受体（TLR），特别是TLR 2，在神经炎症中起重要作用。然而，TLR 2参与CIH诱导的认知障碍的机制仍不清楚。在这项研究中，野生型（WT）和TLR 2基因敲除（KO）小鼠暴露于CIH 8周，其社会新奇辨别，空间学习和记忆严重受损。此外，在海马的CA 1和齿状回（DG）区域观察到严重受损的神经元和异常激活的胶质细胞。从机制上讲，敲除TLR 2基因显著减轻了这些病理变化，并改善了行为表现。总之，这些发现表明TLR 2-MyD 88信号通路可能在CIH诱导的认知缺陷中发挥重要作用。
Chronic intermittent hypoxia (CIH) is the main symptom of obstructive sleep apnea syndrome (OSAS) and causes neural damage and cognitive deficits via neuroinflammation. Toll-like receptors (TLRs), especially TLR2, play an important role in neuroinflammation. However, the mechanisms by which TLR2 participates in CIH-induced cognitive deficits remain unclear. In this study, wild-type (WT) and TLR2 knock out (KO) mice were exposed to CIH for 8 weeks, and their social novelty discrimination, spatial learning and memory were severely compromised. Additionally, seriously damaged neurons and abnormally activated glia were observed in the CAl and dentate gyrus (DG) areas of the hippocampus. Mechanistically, knocking out the TLR2 gene significantly alleviated these pathological changes and improved the behavioral performance. Together, these findings demonstrate that the TLR2-MyD88 signaling pathway might play an important role in CIH-induced cognitive deficits.