'Young blood reverses age-related brain impairments in old mice'

Date: May-06-2014New research finds infusing aging mice with the blood of young mice appears

to recharge the brain so it functions more like a younger one. Led by Stanford School of Medicine

in California, the study introduces the idea that age-related decline is reversible, pointing the

way to potential new treatments for Alzheimer's disease and other dementias.

In the journal Nature Medicine, senior author Tony Wyss-Coray and colleagues describe how they infused plasma (blood

stripped of cells) from young mice into older mice and found they performed better in spatial

memory tests than older mice that had received plasma from other older mice, or none at all.

The main purpose of the study was to use sophisticated methods to test a number of important

molecular and biological changes that occur in the brains of older mice when they share the blood

of younger mice.

But the team decided to include an extra test on memory performance, and this is how they made

their discovery, as Prof. Wyss-Coray, who is also senior research career scientist at the Veterans

Affairs Palo Alto Health Care System, explains:

"This could have been done 20 years ago. You don't need to know anything about how the brain

works. You just give an old mouse young blood and see if the animal is smarter than before. It's

just that nobody did it."

Study examined pairs of mice with shared blood supply

The study involved examining pairs of mice whose circulation systems were surgically conjoined.

So-called parabiotic mice share a pooled blood supply. The experiments involved two kinds of

pairs: a young mouse paired with an old mouse, and two old mice paired together.

The team has published work on the effect of blood on aging using parabiotic mice before. For

instance, in a study reported in Nature in 2011 they concluded blood factors appear to cause aging in

brains of mice.

In that study, they showed how more new cells grew in key parts of the brain of older mice

paired with young mice than in old mice paired with other old mice. And conversely, they also

found exposing young mice to blood from old mice had the opposite result on nerve cell production,

and the young mice were less able to find their way around their environments.

But what the team had not done previously was measure the effect of young blood on the brains

of the older mice in simple memory tests. In this latest study, they did both - they looked for

changes in brain circuits and cells, and they tested changes in learning and memory.

Researchers focused on changes to the hippocampus

When infused with plasma from younger mice, the older mice performed much better in spatial memory tests.

The researchers were particularly interested in examining what happened to the hippocampus in

the brains of the parabiotic mice. The hippocampus is important for recalling and recognizing

spatial patterns, both in mice and humans.

This part of the brain. Prof. Wyss-Coray explains, is the part you use when you are trying "to

find your car in a parking lot or navigate around a city without using your GPS system."

The hippocampus can change depending on brain activity. For instance, one study found brain changes in London cab

drivers. Trainees who after 3 or 4 years passed the exam called "The Knowledge," showed

an increase in grey matter at the back of the hippocampus compared to the ones who did not pass

the exam.

The hippocampus is also very vulnerable to aging. Its function erodes in all brains as they

age, but it occurs faster in people with dementia like Alzheimer's disease, who eventually cannot

form new memories.

When they looked at the variously paired parabiotic mice, the researchers found consistent

differences in the way the hippocampus behaved biochemically, and electrically, as well as what it

looked like.

Hippocampus was 'younger looking' in older mice infused with young blood

The hippocampi of older mice were more similar to those of younger mice when they were paired

with younger mice than with older mice. Also, when paired with younger mice, the hippocampi of

older mice made more chemicals linked to learning, than those of older mice paired with other

older mice.

The nerve cells in older mice paired with younger mice were also more able to stronger connections to other nerve cells, compared with the nerve cells in the older pairs. These connections are an important feature for making new memories and learning.

Prof. Wyss-Coray says it was "as if these old brains were recharged by young blood."

As well as examining these various changes in the brains of the mice, the team put differently

aged mice through tests where they had to quickly orient themselves in new and challenging situations

- using memory cues from their surroundings.

The older mice, as expected, tended to perform worse than the younger mice, as they did when

infused with plasma from other older mice.

But, when infused with plasma from younger mice, the older mice performed much better.

However, improvement in performance disappeared if the plasma was heated to a high temperature

before being given to the mice. Heat can alter proteins, suggesting proteins in the young blood

infused into the old mice could be responsible for the changes in their cognitive performance.

The team is now trying to discover what these proteins might be, and which tissues they come

from.

Prof. Wyss-Coray is co-founder of Alkahest, a biotechnology company that is exploring the

therapeutic potential of the study. He says they do not yet know if what they found will work in

humans, but is hoping they can set up a trial sooner rather than later.

The US Department of Veteran Affairs, the California Institute for Regenerative Medicine and

the National Institute of Aging helped fund the study.

Written by Catharine Paddock PhD

View all articles written by Catharine, or follow Catharine on:

Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.