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β-chitosan attenuates hepatic macrophage-driven inflammation and reverses aging-related cognitive impairment

Summary

Researchers found that β-chitosan, a compound extracted from squid parietal bone, can reverse age-related memory and learning problems in mice, zebrafish, and worms. The compound works by reducing excessive inflammation in the liver and lowering inflammatory chemicals in the blood, which in turn reduces brain inflammation. This discovery suggests a direct connection between liver health and brain aging, and β-chitosan may offer a new therapeutic approach for age-related cognitive decline.

Background

Aging is accompanied by chronic inflammation that contributes to cognitive impairment. Recent evidence suggests a link between liver abnormal inflammation and cognitive decline, but the mechanistic pathways remain unclear. The liver contains abundant macrophages (Kupffer cells) that may play a role in peripheral inflammation affecting brain function.

Objective

To investigate the mechanistic link between hepatic macrophage activation and neuroinflammation during aging. To determine if β-chitosan can ameliorate age-related cognitive impairment by reducing liver macrophage-driven inflammation through the liver-brain axis.

Results

β-chitosan administration ameliorated cognitive impairment in aged and LPS-stimulated mice by reducing hepatic macrophage activation and decreasing circulating TNF-α and IL-1β levels. Treatment decreased VCAM1 expression on the blood-brain barrier and suppressed neuroinflammation in the hippocampus. Similar beneficial effects were observed in aged zebrafish and C. elegans, with β-chitosan blocking TLR4-MD-2 complex activation via the NF-κB pathway.

Conclusion

β-chitosan reverses aging-related cognitive impairment by attenuating hepatic macrophage-driven inflammation and reducing peripheral pro-inflammatory cytokines, thereby decreasing neuroinflammation through the liver-brain axis. The compound functions by blocking TLR4-MD-2 complex activation, suggesting potential therapeutic application for age-related cognitive decline.
  • Published in:iScience,
  • Study Type:Experimental Research,
  • Source: PMID: 39280626, DOI: 10.1016/j.isci.2024.110766
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