Blood from a baby’s umbilical cord revs up learning and memory ability in older mice, according to a study that holds implications for mind-boosting therapies in humans.
Researchers from the Stanford University School of Medicine identified a specific protein in the plasma of umbilical cord blood that increased cognitive functioning in animal studies. The protein, known as tissue inhibitor of metalloproteases 2, or TIMP2, is abundant in umbilical cord blood but decreases in human blood with age.
Previous studies have investigated TIMP2 but that work has barely scratched the surface of its potential as a cognitive treatment for humans, say researchers.
“Neuroscientists have ignored it and are still ignoring it, but to me it’s remarkable that something in your blood can influence the way you think,” said senior author Dr. Tony Wyss-Coray, professor of Neurology and Neurological Sciences with Stanford University School of Medicine and a senior research career scientist at the Veterans Affairs Palo Alto Health Care System.
For the current study, researchers injected umbilical-cord blood plasma into older mice and tested the animals’ cognitive functioning using a Barnes maze, a test that assesses spatial memory. After two weeks of regular blood infusions, older mice that received umbilical cord blood showed significant performance improvements over mice that received only saline injections.
When the scientists looked closer, they discovered that activity in the hippocampus of the mice that received the blood infusions was spiking, essentially returning to neurological levels seen at a younger age. Despite being critical to learning and memory, the hippocampus is a part of the brain that can develop wear and tear.
“The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation,” report the study authors in the journal Nature.
In other words, “with advancing age, the hippocampus degenerates, loses nerve cells and shrinks,” said Wyss-Coray.
With that shrinking comes a decrease in one’s ability to learn new things and store memories. By improving hippocampal functioning in older mice, the researchers staved off normal signs of aging and returned the brain to previous levels of learning capacity.
A key development in the latest study is the isolation of TIMP2, which the researchers also tested on memory processing in mice. Directly injecting the TIMP2 protein into older mice had the same effect as infusing the blood plasma — it restored early-life cognitive functioning.
“TIMP2’s effects in the brain have been studied a little, but not much and not in aging,” said Dr. Joseph Castellano, an instructor of Neurology and Neurological Sciences. “In our study, it mimicked the memory and learning effects we were getting with cord plasma. And it appeared to do that by improving hippocampal function.”
During the study, the researchers compared the composition of blood plasma among different age groups, including newborns, 19- to 24-year-olds and 61- to 82-year-olds. They found that levels of TIMP2 decrease naturally with age.
As a signal that TIMP2 may hold future therapy promise, Stanford has filed for patents related to the research, and a biotechnology company called Alkahest, which both Castellano and Wyss-Coray are involved in, has already licensed rights.