Monocyte NLRP3-IL-1β Hyperactivation Mediates Neuronal and Synaptic Dysfunction in Perioperative Neurocognitive Disorder.

ABSTRACT: Perioperative neurocognitive disorder may develop in vulnerable patients following major operation. While neuroinflammation is linked to the cognitive effects of surgery, how surgery and immune signaling modulate neuronal circuits, leading to learning and memory impairment remains unknown. Using in vivo two-photon microscopy, Ca²⁺ activity and postsynaptic dendritic spines of layer 5 pyramidal neurons in the primary motor cortex of a mouse model of thoracic surgery are imaged. It is found that surgery causes neuronal hypoactivity, impairments in learning-dependent dendritic spine formation, and deficits in multiple learning tasks. These neuronal and synaptic alterations in the cortex are mediated by peripheral monocytes through the NLRP3 inflammasome-dependent IL-1β production.

SUBMITTER: Chen K 

PROVIDER: S-EPMC9165480 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature