Dysfunction of inflammation-resolving pathways is associated with postoperative cognitive decline in elderly mice

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Postoperative cognitive dysfunction (POCD) is a reversible mental disorder increasing mortality risk in elderly patients.
• The cholinergic anti-inflammatory pathway (CAP) is crucial for managing neuroinflammation and cognitive decline after sterile trauma.
• This study investigates the link between POCD in elderly mice and CAP dysfunction.

Purpose of the Study:

• To determine if POCD in elderly mice is associated with cholinergic anti-inflammatory pathway (CAP) dysfunction.
• To evaluate the impact of aging on cognitive function and inflammatory responses post-surgery.
• To assess the efficacy of alpha7 nicotinic acetylcholine receptor agonists in reversing POCD and inflammation.

Main Methods:

• Elderly and adult mice underwent sham surgery or surgical procedures.
• Cognitive function was assessed 24 hours post-surgery.
• Pro-inflammatory cytokines (TNF-α, IL-6, IL-10), M2 macrophages in the hippocampus, and CD11b/c+α7 nAChR+ cells in spleens were measured.

Main Results:

• Elderly mice exhibited significantly higher POCD compared to adult mice 24 hours post-surgery.
• Elevated pro-inflammatory cytokines (TNF-α, IL-6) and reduced anti-inflammatory cytokine (IL-10) and M2 macrophages were observed in elderly mice.
• A reduced population of CD11b/c+α7 nAChR+ splenocytes was found in elderly mice post-surgery.

Conclusions:

• Dysfunction of the cholinergic anti-inflammatory pathway (CAP) is associated with exaggerated cognitive decline and inflammation in elderly mice post-surgery.
• Alpha7 nicotinic acetylcholine receptor agonists effectively reversed the cognitive and inflammatory deficits in elderly mice.
• Targeting the CAP may offer a therapeutic strategy for preventing and treating POCD in the elderly.