Inhibition of STAT3 signal pathway recovers postsynaptic plasticity to improve cognitive impairment caused by chronic intermittent hypoxia.
Sleep Breath
; 27(3): 893-902, 2023 06.
Article
en En
| MEDLINE
| ID: mdl-35871214
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Apnea Obstructiva del Sueño
/
Factor de Transcripción STAT3
/
Disfunción Cognitiva
Límite:
Animals
Idioma:
En
Revista:
Sleep Breath
Asunto de la revista:
NEUROLOGIA
/
OTORRINOLARINGOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China