Purpose

Chronic intermittent hypoxia (CIH) is a major cause of cognitive dysfunction in people with obstructive sleep apnea syndrome (OSAS), as it damages synapse structure, and function. This study aimed to investigate the potential mechanisms resulting in cognitive impairment caused by CIH in patients with OSAS.

Methods

Healthy adult SD male rats (n = 36) were randomly divided into four groups: control, CIH, WP1066, and dimethyl sulfoxide (DMSO). The CIH, WP1066, and DMSO groups were exposed to intermittent hypoxic environments for 8 h per day for 28 d. The WP1066 group received intraperitoneal injection of WP1066, a selective signal transducer and activator of transcription-3 (STAT3) inhibitor. All the experimental rats were subjected to the Morris water maze. Hippocampal tissue samples (n = 6 per group) were used for western blot analysis, and brain tissue samples (n = 3 per group) were used for immunohistochemistry and hematoxylin and eosin staining.

Results

The cognition of rats exposed to prolonged CIH was impaired. P-STAT3 expression was found to be higher in CIH rats than in control rats. Postsynaptic density95 (PSD95) expression was significantly reduced in rats with CIH-induced learning and memory impairment, but it significantly increased after the STAT3 signaling pathway was blocked, which improved learning and memory ability. However, inhibition of the STAT3 signaling pathway failed to improve the decline of synaptophysin (SYP) protein caused by CIH.

Conclusions

When rats are exposed to CIH, STAT3 in the brain is activated, PSD95 and SYP levels decrease, and cognition is impaired. Inhibition of the STAT3 signaling pathway increases PSD95 to recover postsynaptic plasticity, thereby improving cognitive dysfunction.

中文翻译：

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抑制STAT3信号通路恢复突触后可塑性改善慢性间歇性缺氧引起的认知障碍

目的

慢性间歇性缺氧 (CIH) 是阻塞性睡眠呼吸暂停综合征 (OSAS) 患者认知功能障碍的主要原因，因为它会损害突触结构和功能。本研究旨在探讨 CIH 导致 OSAS 患者认知障碍的潜在机制。

方法

健康成年 SD 雄性大鼠 ( n  = 36) 随机分为四组：对照组、CIH、WP1066 和二甲基亚砜 (DMSO)。CIH、WP1066 和 DMSO 组暴露于间歇性低氧环境，每天 8 小时，持续 28 天。WP1066 组接受腹腔注射 WP1066，一种选择性信号转导和转录激活因子 3 (STAT3) 抑制剂。所有实验大鼠均进行 Morris 水迷宫。海马组织样本（每组n  = 6）用于蛋白质印迹分析，脑组织样本（每组n  = 3）用于免疫组织化学和苏木精和伊红染色。

结果

暴露于长时间 CIH 的大鼠的认知受损。发现 CIH 大鼠的 P-STAT3 表达高于对照大鼠。CIH诱导的学习记忆障碍大鼠突触后密度95（PSD95）表达显着降低，但在阻断STAT3信号通路后显着升高，从而提高学习记忆能力。然而，抑制STAT3信号通路未能改善由CIH引起的突触素（SYP）蛋白的下降。

结论

当大鼠暴露于 CIH 时，大脑中的 STAT3 被激活，PSD95 和 SYP 水平降低，认知受损。抑制 STAT3 信号通路可增加 PSD95 以恢复突触后可塑性，从而改善认知功能障碍。