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Alzheimer's, Dementia & Mental Health
Drug Fully Reverses Age-Related Memory Loss by
Triggering Natural Mechanism
Study with rats shows ampakines boost brain’s
protein in government financed study
July 27, 2006 - A drug made to enhance memory
appears to trigger a natural mechanism in the brain that fully reverses
age-related memory loss, even after the drug itself has left the body,
according to researchers at UC Irvine. “This is a significant
discovery,” said Christine Gall, professor of anatomy and neurobiology.
“Our results indicate the exciting possibility that ampakines could be
used to treat learning and memory loss associated with normal aging.”
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Professors Gall and Gary Lynch, along with
Associate Researcher Julie Lauterborn, were among a group of scientists
who conducted studies on rats with a class of drugs known as ampakines.
Ampakines were developed in the early 1990s by UC researchers, including
Lynch, to treat age-related memory impairment and may be useful for
treating a number of central nervous system disorders, such as
Alzheimer’s disease and schizophrenia.
In this study, the researchers showed that ampakine
drugs continue to reverse the effects of aging on a brain mechanism
thought to underlie learning and memory even after they are no longer in
the body. They do so by boosting the production of a naturally occurring
protein in the brain necessary for long-term memory formation.
The study appears in the August issue of the
Journal of Neurophysiology.
The researchers treated two groups of middle-aged
rats twice a day for four days with either a solution that contained
ampakines or one that did not. They then studied the hippocampus region
of the rats’ brains, an area critical for memory and learning. They
found that in the ampakine-treated rats, there was a significant
increase in the production of brain-derived neurotrophic factor (BDNF),
a protein known to play a key role in memory formation.
They also found an increase in long-term
potentiation (LTP), the process by which the connection between the
brain cells is enhanced and memory is encoded. This enhancement is
responsible for long-term cognitive function, higher learning and the
ability to reason. With age, deficits in LTP emerge, and learning and
memory loss occurs.
Significantly, restoration of LTP was found in the
middle-aged rats’ brains even after the ampakines had been cleared from
the animals’ bodies. The drug used in the injections has a half-life of
only 15 minutes; the increase in LTP was seen in the rats’ brains more
than 18 hours later.
According to the researchers, this study suggests
that pharmaceutical products based on ampakines can be developed that do
not need to be in the system at all times in order to be effective.
Most drugs used to deal with central nervous system
disorders, such as Parkinson’s disease, are only effective when they are
in the body. Further studies will be needed to determine exactly how
long the effect on LTP will be maintained after the ampakines leave the
system.
The lingering presence of LTP also appears to
contribute to BDNF remaining in the body, researchers said. “Ampakines
work in two important ways to improve learning and memory,” Lauterborn
said.
“They directly stimulate the connection between
nerve cells, which has an immediate effect of boosting LTP. But they
also increase the presence of this important protein, BDNF, that can
stay in the body and keep boosting memory after the drug has worn off.”
Notes:
Collaborators on the study were
Christopher Rex, Ching-Yi Lin, Eniko A. Kramar and Gary Rogers of Cortex
Pharmaceuticals.
The study was funded by grants from
the National Institute of Neurological Disorders and Stroke, the
National Institute on Aging, and from National Institute of Mental
Health. The ampakine drug was provided by Cortex.
About the University of California,
Irvine: The University of California, Irvine is a top-ranked university
dedicated to research, scholarship and community service. Founded in
1965, UCI is among the fastest-growing University of California
campuses, with more than 24,000 undergraduate and graduate students and
about 1,400 faculty members. The second-largest employer in dynamic
Orange County, UCI contributes an annual economic impact of $3.3
billion.
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