Neuroscience: Cognitive decline eased by boosting macrophage metabolism

Cognitive decline can be reversed in mice by treating them with a drug that reduces inflammation and boosts the metabolism of immune cells called macrophages, according to a paper published this week in Nature. The study highlights some of the key changes that underpin age-related cognitive decline, and suggests that the condition may not be permanent.

Low-grade inflammation is a key feature of ageing that is thought to contribute to many age-related disorders such as cognitive decline, neurodegeneration and atherosclerosis. The mechanisms that initiate and sustain these changes have been unclear, but Katrin Andreasson and colleagues highlight a potential role for macrophages. The macrophages of ageing mice have a lower metabolic rate than those of younger mice, and show high levels of a pro-inflammatory molecule called prostaglandin E2 (PGE2). The authors demonstrate that when mice are treated with a drug that suppresses PGE2 signalling, cellular metabolism is restored to youthful levels and inflammation is reduced. In addition, inhibiting PGE2 signalling in mice reverses age-related deficits in tests of spatial memory, and restores function and flexibility to the hippocampus—a region of the brain that is important for learning and memory.

The study suggests that age-related cognitive decline does not have to be a static or permanent condition, and that inhibiting PGE2 signalling can reverse cognitive ageing.