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Inhibition of STAT3 signal pathway recovers postsynaptic plasticity to improve cognitive impairment caused by chronic intermittent hypoxia

  • Sleep Breathing Physiology and Disorders • Original Article
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Abstract

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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This research was supported by the National Natural Science Foundation of China (81660194). The present study was also supported by the Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China, 563003. We thank all the partners and staff who helped us in the process of this study.

Funding

The National Natural Science Foundation of China provided financial support in the form of grant funding (Grant No: 81660194). The sponsor had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou, 563003, China

    Jin Wang, Zucai Xu, Ling Xu & Ping Xu

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  1. Jin Wang
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  2. Zucai Xu
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  3. Ling Xu
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Correspondence to Ping Xu.

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Wang, J., Xu, Z., Xu, L. et al. Inhibition of STAT3 signal pathway recovers postsynaptic plasticity to improve cognitive impairment caused by chronic intermittent hypoxia. Sleep Breath 27, 893–902 (2023). https://doi.org/10.1007/s11325-022-02671-6

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  • DOI: https://doi.org/10.1007/s11325-022-02671-6

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