In mice, TIMP2 protein improved the function of brain immune cells — ScienceDaily

Scientists at the Icahn School of Medicine at Mount Sinai found that the TIMP2 protein is associated with maintaining normal microglial function — the brain’s immune cells. Administering TIMP2 to older mice helped these cells more effectively clear tissue of cellular debris and reduced molecular signs of inflammation, ScienceDaily reports.

What happens without TIMP2

The study results were published in the journal Nature Communications. Microglia perform protective and maintenance functions in the brain: they remove cellular waste, support networks of connections between neurons, and respond to tissue damage. With age, these cells may become less effective at their tasks and may also shift into states associated with inflammation.

The researchers analyzed several groups of mice, including genetically modified animals lacking TIMP2 throughout the body, as well as models in which the protein was removed only from microglia or neurons. They used single-nucleus RNA sequencing, imaging, functional tests, and microdialysis in living brain tissue for the analysis.

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In the absence of TIMP2, microglia acquired traits characteristic of aging and brain damage: their ability to clear cellular remnants declined, and molecular signatures of cellular senescence emerged. In the brain’s extracellular environment, the scientists also detected higher levels of proteins associated with inflammation and stress.

Results of administering the protein to older mice

At the next stage, the team administered TIMP2 to older mice by injection so that the protein would circulate in the bloodstream. Afterward, microglia cleared cellular debris more effectively, while markers associated with inflammatory states decreased.

The authors believe that TIMP2 may support the protective functions of microglia and limit their potentially harmful responses. At the same time, the results were obtained in experiments on mice. Whether TIMP2 will have a similar effect in humans and whether the protein itself or related biological pathways can be used to treat age-related brain changes still requires separate research.