DISAMPING KANAN INI.............
PLEASE USE ........ "TRANSLATE MACHINE" .. GOOGLE TRANSLATE BESIDE RIGHT THIS
..................
Infusion
of young blood recharges brains of old mice
Date:
May 5, 2014
Source:
Stanford University Medical Center
Summary:
Something -- or some things -- in the blood of young
mice has the ability to restore mental capabilities in old mice, a new study
has found. If the same goes for humans, it could spell a new paradigm for
recharging our aging brains, and it might mean new therapeutic approaches for
treating dementias such as Alzheimer's disease.
............................
Something -- or some things -- in the blood of young mice
has the ability to restore mental capabilities in old mice, a new study by
Stanford University School of Medicine investigators has found.
If the same
goes for humans, it could spell a new paradigm for recharging our aging brains,
and it might mean new therapeutic approaches for treating dementias such as
Alzheimer's disease.
In the
study, to be published online May 4 in Nature Medicine, the researchers
used sophisticated techniques to pin down numerous important molecular, neuroanatomical
and neurophysiological changes in the brains of old mice that shared the blood
of young mice.
But they
also conducted a critical experiment that was far from sophisticated, said Tony
Wyss-Coray, PhD, the senior author of the study and a professor of neurology
and neurological sciences. The scientists simply compared older mice's
performance on standard laboratory tests of spatial memory after these mice had
received infusions of plasma (the cell-free part of blood) from young versus
old mice, or no plasma at all.
"This
could have been done 20 years ago," said Wyss-Coray, who is also senior
research career scientist at the Veterans Affairs Palo Alto Health Care System.
"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."
Wyss-Coray
has co-founded a biotechnology company, Alkahest, to explore the therapeutic
implications of the new study's findings. He serves as the director of Alkahest's
scientific advisory board.
The study's
lead author, Saul Villeda, PhD, now has an active lab of his own as a faculty
fellow in anatomy at the University of California-San Francisco. Villeda was a
graduate student at Stanford and, briefly, a postdoctoral scholar under
Wyss-Coray's direction when the bulk of the work was performed.
"We've
shown that at least some age-related impairments in brain function are
reversible. They're not final," Villeda said.
Previous
experiments by Wyss-Coray, Villeda and their colleagues, described in a paper
published in 2011 in Nature, had revealed that key regions in the brains
of old mice exposed to blood from young mice produced more new nerve cells than
did the brains of old mice similarly exposed to blood from old mice.
Conversely, exposing young mice to blood from old mice had the opposite effect
with respect to new nerve-cell production, and also reduced the young mice's
ability to navigate their environments.
But that
earlier work didn't directly assess the impact of young mouse blood on older
mice's behavior. This time, the researchers checked both for changes within
nerve circuits and individual nerve cells and for demonstrable improvements in
learning and memory. First, they examined pairs of mice whose circulatory
systems had been surgically conjoined. Members of such pairs, known as
parabiotic mice, share a pooled blood supply.
Wyss-Coray's
group paid special attention, in these parabiotic mice, to a brain structure
called the hippocampus. In both mice and humans, this structure is critical for
forming certain types of memories, notably the recollection and recognition of
spatial patterns. "That's what you need to use when, for example, you try
to find your car in a parking lot or navigate around a city without using your
GPS system," Wyss-Coray said.
Experience
alters hippocampal activity and anatomy. Studies have found, for instance, that
a veteran London cabdriver's hippocampus is larger than it was when the driver
was first hired, and larger than the average person's. The hippocampus is also
extremely vulnerable to the normal aging process, showing early erosion in
function as people grow older. In dementias such as Alzheimer's disease, this
hippocampal deterioration is accelerated, leading to an inability to form new
memories.
"We
know that detrimental anatomical and functional changes occur in the
hippocampus as mice and people get older," said Villeda. "This is
just from natural aging. We're all heading in that direction."
When the
investigators compared hippocampi from old mice whose circulatory systems had
been conjoined with those of young mice to hippocampi from old mice that had
been paired with other old mice, they found consistent differences in a number
of biochemical, anatomical and electrophysiological measures known to be
important to nerve-cell circuits' encoding of new experiences for retention in
the cerebral cortex.
The
hippocampi of older mice that had been conjoined to younger mice more closely
resembled those of younger mice than did the hippocampi of older mice similarly
paired with old mice. The old mice paired with young mice made greater amounts
of certain substances that hippocampal cells are known to produce when learning
is taking place, for example. Hippocampal nerve cells from older members of
old-young parabiotic pairs also showed an enhanced ability to strengthen the
connections between one nerve cell and another -- essential to learning and
memory.
"It was
as if these old brains were recharged by young blood," Wyss-Coray said.
Villeda,
Wyss-Coray and their associates next subjected regular older mice to a test in
which the mice were trained to quickly locate a submerged platform in a
water-filled container. The mice had to speedily orient themselves using memory
cues provided by their surroundings. The investigators injected old mice
intravenously with plasma from young or old mice and ran them through the test.
Typically, untreated older mice did poorly compared to young mice, as they did
when injected with plasma from old mice. But if they were infused with young
mice's plasma they did much better.
This was
likewise the case on another test in which mice were trained to freeze in fear
when plunked into a particular environment. The better they recognized that
environment, the longer they would freeze. Older mice typically freeze for a
shorter period of time than younger ones do. Again, "freezing" times
for older mice given young plasma, but not old plasma, increased significantly.
In both
tests, the improvement vanished if the plasma provided to the old mice had
first been subjected to high temperatures. Heat treatment can denature
proteins, so this hints that a blood-borne protein, or group of them, may be
responsible for the cognitive improvements seen in old mice given young mouse
plasma.
"There
are factors present in blood from young mice that can recharge an old mouse's
brain so that it functions more like a younger one," Wyss-Coray said.
"We're working intensively to find out what those factors might be and
from exactly which tissues they originate."
"We
don't know yet if this will work in humans," he said, adding that he hopes
to find out sooner rather than later. A near-term goal of his company is to
test this proposition through a clinical trial.
Story
Source:
The above
story is based on materials
provided by Stanford
University Medical Center. Note: Materials may be edited for content
and length.
Journal
Reference:
- Saul A Villeda, Kristopher E Plambeck, Jinte Middeldorp, Joseph M Castellano, Kira I Mosher, Jian Luo, Lucas K Smith, Gregor Bieri, Karin Lin, Daniela Berdnik, Rafael Wabl, Joe Udeochu, Elizabeth G Wheatley, Bende Zou, Danielle A Simmons, Xinmin S Xie, Frank M Longo, Tony Wyss-Coray. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature Medicine, 2014; DOI: 10.1038/nm.3569
Cite This
Page:
Stanford University Medical Center.
"Infusion of young blood recharges brains of old mice." ScienceDaily.
ScienceDaily, 5 May 2014. <www.sciencedaily.com/releases/2014/05/140505094906.htm>.