Memory Decline in Seniors May Be Reversed by New
The drug the researchers tested blocked GABA
receptors, restoring working memory in aged rats to the level of younger
March 8, 2014 - It may seem normal, at least for
senior citizens - as we age, we misplace car keys, or can’t remember a
name we just learned, or a meal we just ordered. But University of
Florida researchers say memory trouble doesn’t have to be inevitable for
seniors, and they’ve found a drug therapy that could potentially reverse
this type of memory decline.
The drug can’t yet be used in humans, but the
researchers are pursuing compounds that could someday help the
population of aging adults who don’t have Alzheimer’s or other dementias
but still have trouble remembering day-to-day items. Their findings were
published in the March 5 issue of the Journal of Neuroscience.
The kind of memory responsible for holding
information in the mind for short periods of time is called “working
memory.” Working memory relies on a balance of chemicals in the brain.
The UF study shows this chemical balance tips in older adults, and
working memory declines. The reason could be because their brains are
producing too much of a chemical that slows neural activity.
“Graduate student Cristina Banuelos’ work suggests
that cells that normally provide the brake on neural activity are in
overdrive in the aged prefrontal cortex,” said researcher Jennifer Bizon,
Ph.D., an associate professor in the department of neuroscience and a
member of UF’s Evelyn F. & William L. McKnight Brain Institute.
This chemical, an inhibitory brain neurotransmitter
called GABA, is essential. Without it, brain cells can become too
active, similar to what happens in the brains of people with
schizophrenia and epilepsy. A normal level of GABA helps maintain the
optimal levels of cell activation, said collaborator Barry Setlow,
Ph.D., an associate professor in UF’s departments of psychiatry and
Working memory underlies many mental abilities and
is sometimes referred to as the brain’s mental sketchpad, Bizon said.
For example, Bizon said, you use your working
memory in many everyday activities such as calculating your final bill
at the end of dining at a restaurant. Most people can calculate a 15
percent tip and add it to the cost of their meal without pencil and
paper. Central to this process is the ability to keep multiple pieces of
information in mind for a short duration — such as remembering the cost
of your dinner while calculating the amount needed for the tip.
“Almost all higher cognitive processes depend on
this fundamental operation,” Bizon said.
To determine the culprit behind working memory
decline, the researchers tested the memory of young and aged rats in a
“Skinner box.” In the Skinner box, rats had to remember the location of
a lever for short periods of up to 30 seconds. The scientists found that
while both young and old rats could remember the location of the lever
for brief periods of time, as those time periods lengthened, old rats
had more difficulty remembering the location of the lever than young
But not all older rats did poorly on the memory
test, just as not all older adults have memory problems. The study shows
the older brains of some people or rats with no memory problems might
compensate for the overactive inhibitory system - they are able to
produce fewer GABA receptors and therefore bind less of the inhibitory
Older rats with memory problems had more GABA
receptors. The drug the researchers tested blocked GABA receptors,
mimicking the lower number of those receptors that some older rats had
naturally and restoring working memory in aged rats to the level of
“Modern medicine has done a terrific job of
keeping us alive for longer, and now we have to keep up and determine
how to maximize the quality of life for seniors,” Bizon said. “A key
aspect of that is going to be developing strategies and therapies that
can maintain and improve cognitive health.”
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