Protein in umbilical cord blood may restore the aging brain

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The promise of young-blood injections to keep us sharp has captivated Silicon Valley, but the studies have all been with mice blood - until now. Researchers from the University of Stanford have discovered that proteins taken from umbilical cord blood and then injected into the brain rejuvenate elderly mice.

The discovery started with an experiment dating back to 2014, when Tony Wyss-Coray, a professor of neurology at Stanford, and colleagues found that transfusing blood from young mice into old mice perked up the older mice, boosting both muscle strength and memory.

When the older mice received human umbilical-cord blood plasma every fourth day for two weeks, many measures of hippocampal function improved notably. The lead author of the study was Joseph Castellano, Ph.D., an instructor of neurology and neurological sciences.

The new study demonstrates that human plasma can also improve the memory and learning of older mice.

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Researchers found that a specific change in the number of proteins found in plasma could be identified between groups ranging from 19 to 24 years of age and 61 to 82 year-olds. Harvard neuroscientist Lee Rubin, a coauthor of some of the GDF11 work, told Science that the new data suggests that "it isn't just one thing". The lower the age at which the plasma is collected, the higher are its benefits. And the researcher found that blocking TIMP2 in young mice seemed to prematurely age their memories.

Next, the scientists used a device called a protein micro-ray to analyze the amounts of different proteins in the blood. Those proteins, in turn, have the task of "chopping up" yet more proteins that exist in the matrix surrounding body cells.

This indicates that blood from the younger population may be more effective in repairing memory.

The hippocampus is a brain region that converts experiences into long-term memories and plays a particularly important role in spatial memory, which helps a person remember information such as where they parked their vehicle in a multi-storey auto park or what they ate for breakfast. First, the mice with destroyed immune systems are so sick to begin with that the good results might not be very representative. More studies are needed if the findings of the study could be applied to people with dementia. The lesson from Alzheimer's research on mice is that nearly everything works in the animals, and so far nothing works in humans, said Rob Howard, professor of old age psychiatry at University College London.

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A classic laboratory test of a mouse's spatial memory is called the Barnes maze. Numerous earlier studies relied on a process called parabiosis, in which pairs of young and old mice had their veins and blood supplies connected. And administering TIMP2-neutralizing antibodies to young normal mice, who ordinarily perform well on memory tests, obliterated their prowess.

For example, they watched how long it took the mice to escape from a maze the mice had done before, using visual cues to choose an exit that would lead to safety.

Still, injections of donated cord blood plasma may not be the wonder-drug they sound like. Afterwards, the researchers compared those mice with those in three other groups: those that got blood plasma from young adults, those that got plasma from older people, and those in a control group that only got saline. Or, maybe TIMP2 from cord blood doesn't make it to the brain, or maybe a different protein is the right one.

What's more, antibodies against TIMP2 suppressed LTP in hippocampal slices from wild-type mice, and worsened their performance in an object-recognition task.

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