More Commentary on the Role of PF4 in Reducing Brain Inflammation

Platelets in the blood are not just involved in clotting. Near every aspect of our biology has evolved many different functions, and the complexity of our biochemistry is still far from fully explored. Increased platelet factor 4 (PF4) shows up as a feature in a number of different interventions known to reduce inflammation in the aging brain. Researchers are now moving in the direction of developing therapies for neurodegenerative conditions based on the upregulation of PF4 or the delivery of recombinant PF4.

Platelets are a component of blood best known for their role in clotting, but research in recent years has illuminated other functions beyond the traditional part they play in healing wounds. Each platelet contains more than 1,000 bioactive molecules, known as platelet factors, that get released in different combinations when platelets are activated.

Several years ago, researchers discovered some of the first hints that one of those hundreds of molecules, PF4, might be particularly important. The group was trying to explain why exercise increases neurogenesis in the hippocampus, a brain region important for learning and memory. Hypothesizing that something happens in the blood after exercise that affects the brain, researchers first screened the blood of adult mice after they started running on running wheels placed in their cages. They found about 80 factors whose abundance in the blood changed significantly after exercise, and PF4 was among those that rose the most.

When the researchers injected PF4 into the bloodstream of older mice through their tails on a schedule of one injection every third day for 24 days, the old mice behaved much more like young mice in the avoidance task and other memory tests. The findings echoed the cognitive benefits researchers have seen with exercise, which included increased neurogenesis in the brains of the older mice treated with PF4.

While this group was conducting its research linking exercise to PF4 and PF4 to cognition, another team of researchers was trying to identify individual components in young blood that might explain its rejuvenating effects. Inflammation is known to increase with age. In the brain, inflammation activates a type of immune cells called microglia, ultimately leading to neuronal dysfunction and neurodegeneration. Previous studies have shown that injecting old blood into young mice increases inflammation in the young hippocampus. The new study was the first to show that young blood attenuates neuroinflammation and, in turn, reduces the activity of microglia. The injection of platelets alone was enough to have these effects. And the most common protein in the platelet solution, analysis showed, was PF4.

Although PF4 didn't appear to cross the blood-brain barrier, data showed that PF4 affects the peripheral immune system, reducing the number of pro-aging immune factors in circulation, decreasing neuroinflammation and enhancing cognitive function. That sequence of events suggests that both circulating immune factors and the peripheral immune system could be targets of future therapeutics.



Maybe downregulating this could be an treatment after stroke.

Posted by: Renata at March 27th, 2024 9:20 AM
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