Researchers have found that inflamed, senescent microglia excessively prune synapses in the hippocampus, which can lead to cognitive decline, but a senolytic compound has shown promise in mitigating this process.

The study used Black 6 mice exposed to lipopolysaccharides (LPS) to induce neuroinflammation, resulting in significant changes in gene expression related to phagocytosis and senescence in microglia.

This neuroinflammation caused cognitive deficits in the mice, evidenced by their reduced ability to navigate a Y maze and decreased interest in novel objects.

Remarkably, ABT-737 reversed cognitive decline in the LPS-treated mice, restoring their abilities to levels comparable to healthy controls, despite no significant changes in inflammatory biomarkers.

While these findings are promising, they were observed in young mice with induced inflammation, highlighting the need for further research to determine if senolytics can address age-related cognitive decline.

Normally, microglia prune unnecessary synapses during brain development, which is beneficial, but in disease states such as inflammation caused by conditions like blood sepsis, this process can become damaging.

Treatment with the senolytic drug ABT-737 reduced markers of microglial senescence, decreased excessive synapse pruning, and partially restored neuroplasticity, leading to improved cognitive performance.

Analysis revealed that several upregulated genes were involved in debris clearing and phagocytosis, with increased activity in microglia after LPS treatment, indicating heightened microglial activation.