A protein found in high levels in umbilical cord plasma may hold a secret to improving memory and mental activity among aging populations, according to new research.
A team of neuroscientists at Stanford University found that injecting old mice with human umbilical cord plasma significantly improved their memory and testing performance.
While previous studies had shown a positive effect from plasma from young mice injected into old mice, this study is the first to show that human plasma may have the same effect. The implication, according to the study authors, is that such a treatment could have a similar effect on aging humans.
“The big promise is that we’re just now starting to appreciate the untapped potential of what’s circulating throughout the blood supply,” said Joseph Castellano, a neuroscientist at Stanford and lead author of the study.
In their most recent study, a group of older mice received human umbilical cord plasma — the non-cell portion of the blood — every fourth day for two weeks. The injections substantially improved hippocampal function and their performance on memory-based tests, such as the Barnes maze. Another group of older mice receiving plasma injections from older people, by contrast, saw no improvement.
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The addition of young human plasma to the older mice was, in effect, making their brains act younger. To understand why, Castellano and colleagues observed different proteins in the blood that they believed could be playing a role. Comparing blood plasma from umbilical cords, 19- to 24-year-olds, and 61- to 82-year-olds, researchers found age-related changes in a number of proteins.
The same process was true in mice, though researchers were able to identify a single protein, TIMP2, present in both species, which appeared to be undergoing the same aging process. To test the effect of this isolated protein, researchers separated it from the plasma and injected it into old mice in the same manner. The results indicated they were onto something.
“In our study, [TIMP2] mimicked the memory and learning effects we were getting with cord plasma — and it appeared to do that by improving hippocampal function,” Castellano said in a statement.
Injecting TIMP2 by itself into elderly mice multiplied the positive effects seen by the umbilical cord plasma. Among other improvements, researchers observed that TIMP2 injections restored so-called “nesting” instincts lost in old age — the ability of mice to build nests using available materials. Older mice that received TIMP2-depleted plasma showed no learning or memory benefits.
Castellano said that while their team has not examined changes on the cellular level, it might be that the TIMP2 protein remodels the structure — “the scaffolding,” he said — between cells and synapses, increasing the plasticity of the synapses.
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The preliminary results, published in Nature, suggest an important new line of research into the role played by individual molecules in the aging of the hippocampus, part of the brain considered essential to the conversion of experience to long-term memory and especially spatial information, such as where to find your parked car in a multistory building.
“For largely unknown reasons, the hippocampus is especially vulnerable to normal aging,” Tony Wyss-Coray, Stanford neuroscientist and the study’s senior author, said in a statement. "The capacity to learn and remember falters in lockstep.”
The deterioration of the hippocampus is an early manifestation of Alzheimer’s disease, which currently affects an estimated 5.4 million Americans, according to the US Centers for Disease Control and Prevention. While its too early to be sure, better understanding the process that leads to Alzheimer’s, according to Castellano, is another big promise of their research.
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