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 Easter Island Drug Raises Cognition Throughout Life Span in Mice

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PostSubject: Easter Island Drug Raises Cognition Throughout Life Span in Mice   Sun Jul 01, 2012 2:31 pm

Cognitive skills such as learning and memory diminish with age in
everyone, and the drop-off is steepest in Alzheimer's disease. Texas
scientists seeking a way to prevent this decline reported exciting
results this week with a drug that has Polynesian roots.

The researchers, appointed in the School of Medicine at The
University of Texas Health Science Center San Antonio, added rapamycin
to the diet of healthy mice throughout the rodents' life span.
Rapamycin, a bacterial product first isolated from soil on Easter
Island, enhanced learning and memory in young mice and improved these
faculties in old mice, the study showed.

"We made the young ones learn, and remember what they learned, better
than what is normal," said Veronica Galvan, Ph.D., assistant professor
of physiology at the Barshop Institute for Longevity and Aging Studies,
part of the UT Health Science Center. "Among the older mice, the ones
fed with a diet including rapamycin actually showed an improvement,
negating the normal decline that you see in these functions with age."

The drug also lowered anxiety and depressive-like behavior in the
mice, Dr. Galvan said. Anxiety and depression are factors that impair
human cognitive performance. Lead author Jonathan Halloran conducted
scientifically reliable tests to accurately measure these cognitive
components in the rodents.

Venturing into the open

Mice are burrowers that prefer tunnels with walls. To observe
behavior, Halloran used an elevated maze of tunnels that led to a
catwalk. "All of a sudden the mice are in open space," Halloran said.
"It's pretty far from the floor for their size, sort of like if a person
is hiking and suddenly the trail gets steep. It's pretty far down and
not so comfortable."

Mice with less anxiety were more curious to explore the catwalk. "We
observed that the mice fed with a diet containing rapamycin spent
significantly more time out in the open arms of the catwalk than the
animals fed with a regular diet," Halloran said.

The second test measured depressive-like behavior in the rodents.
Mice do not like to be held by their tails, which is the way they are
moved from cage to cage. Inevitably they struggle to find a way out. "So
we can measure how much and how often they struggle as a measure of the
motivation they have to get out of an uncomfortable situation," Dr.
Galvan said.

Rapamycin acts like an antidepressant

Some mice barely struggle to get free, but if an antidepressant is
administered they struggle a lot more. This behavior is very sensitive
to the action of antidepressants and is a reliable measure of whether a
drug is acting like an antidepressant, Dr. Galvan said.

"We found rapamycin acts like an antidepressant -- it increases the
time the mice are trying to get out of the situation," she said. "They
don't give up; they struggle more."

The reductions of anxiety and depressive-like behavior in
rapamycin-treated mice held true for all ages tested, from 4 months of
age (college age in human years) to 12 months old (the equivalent of
middle age) to 25 months old (advanced age).

Feel-good chemicals elevated

The researchers measured levels of three "happy, feel-good"
neurotransmitters: serotonin, dopamine and norepinephrine. All were
significantly augmented in the midbrains of mice treated with rapamycin.
"This is super-interesting, something we are going to pursue in the
lab," Dr. Galvan said.

Dr. Galvan and her team published research in 2010 showing that
rapamycin rescues learning and memory in mice with Alzheimer's-like
deficits. The elevation of the three neurotransmitters, which are
chemical messengers in the brain, may explain how rapamycin accomplished
this, Dr. Galvan said.

Rapamycin is an antifungal agent administered to transplant patients
to prevent organ rejection. The drug is named for Rapa Nui, the
Polynesian title for Easter Island. This island, 2,000 miles from any
population centers, is the famed site of nearly 900 mysterious
monolithic statues.

This study became available online June 28 as a manuscript in press in the journal Neuroscience.
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