NLRP3-GSDMD-dependent IL-1ß Secretion from Microglia Mediates Learning and Memory Impairment in a Chronic Intermittent Hypoxia-induced Mouse Model.
Neuroscience
; 539: 51-65, 2024 Feb 16.
Article
en En
| MEDLINE
| ID: mdl-38154620
ABSTRACT
Hypoxia/reoxygenation caused by chronic intermittent hypoxia (CIH) plays an important role in cognitive deficits in patients with obstructive sleep apnea. However, the precise underlying mechanism remains unclear. This study investigated whether the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is involved in CIH-induced spatial learning and memory impairment in mice, and the possible underlying upstream and downstream mechanisms. The C57BL/6 male mice were exposed to CIH (21% O2-6% O2, 4 min/cycle, 8 h/day) for 9 weeks to investigate the role of NLRP3 in CIH-induced spatial learning and memory impairment in mice. BV2 cells were exposed to intermittent hypoxia (21% O2-1% O2, 90 min/cycle) for 48 h to investigate the possible mechanisms in vitro. We found that 1) inhibition of NLRP3 inflammasome activation improved CIH-induced spatial learning and memory impairment in mice. 2) CIH damaged hippocampal neurons but increased the number of microglia in mice hippocampi; CIH activated microglia-specific NLRP3 inflammasome, leading to upregulation of matured IL-1ß and N-GSDMD. 3) intermittent hypoxia activated NLRP3 inflammasome via the ROS-NF-κB signaling pathway to promote the release of matured IL-1ß from microglia in a GSDMD-dependent manner without pyroptosis. 4) The IL-1ß released from microglia might impair the synaptic plasticity of hippocampal CA3-CA1 synapses by acting on IL-1 receptors in hippocampal neurons. Our findings reveal that ROS-NF-κB-NLRP3 inflammasome-GSDMD dependent IL-1ß release from microglia may participate in CIH-induced spatial learning and memory impairment by acting on hippocampal neuronal IL-1 receptor, leading to synaptic plasticity impairment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inflamasomas
/
Proteína con Dominio Pirina 3 de la Familia NLR
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos