Compounds May Help People Remember
By Eva Emerson
The latest work of USC College neuroscientist Michel Baudry tempers
the good with the bad. The bad news, for mice at least, is that mild
memory loss begins earlier in life than previously thought. The good
news is that two experimental compounds Baudry, professor of biological
sciences, has helped to develop can prevent that memory loss. And while
his results apply to mice, not humans, they do support the notion that
in the future drugs may help people halt the memory loss that has been
an unavoidable consequence of aging.
Beyond its implications for those battling the loss of memory, Baudry’s
work gives new support to a leading theory of aging and points to early
middle age as the time when the first cognitive declines begin.
“This was definitely one of our more dramatic results,” says Baudry,
who did the research with then graduate student Ruolan Liu–the paper’s
first author and currently a postdoctoral fellow in Baudry’s lab–as
well as colleagues from USC, UC Irvine and Eukarion, Inc. (a company
co-founded by Baudry). The findings appear in the June 18 issue of the
Proceedings of the National Academy of Sciences.
One popular explanation of aging posits that aging results from
oxidative damage—itself caused by destructive forms of oxygen called
free radicals formed as a by-product of metabolism. Free radicals wreak
havoc on cells by damaging key molecules such as DNA, proteins and
fats. Dependent on oxygen, the body makes its own antioxidants (such as
catalase and superoxide dismutase) designed to capture free radicals
and render them harmless.
In the study, Baudry’s team looked at the effects of two antioxidant
compounds, EUK-189 and EUK-207, on memory in middle-aged mice.
They trained 120 eight-month-old mice to associate a tone with a mild
electric shock. The mice learned to react fearfully (freezing in place)
whenever they heard the tone or were put into the training cage,
whether or not a shock followed. Researchers tested memory by tracking
how long mice froze when placed in the cage or hearing the tone—those
that froze the longest had the sharpest memory.
After three months, the team compared memory function in groups treated
with one of the two compounds to those of an untreated control group.
Memory significantly declined in the untreated mice, while the treated
groups fared much better. Mice treated with EUK-207, for example,
scored three times higher than controls of the same age in the cage
test, with an ability to remember equal to that of younger,
eight-month-old mice.
“We found that these drugs prevent the age-related decline in memory,”
says Richard F. Thompson, the William M. Keck Chair in Biological
Sciences and professor of psychology in the College, who took part in
the research.
In his study, Baudry found strong evidence that the antioxidant
compounds protected the brain from oxidative assaults, preventing
damage and maintaining memory. To measure the drugs’ ability to sop up
reactive oxygen, the team analyzed the brain tissue from the mice,
looking for telltale signs of oxidative damage. Overall, treated mice
showed fewer signs of damage than controls, with cells of the older,
treated mice most closely resembling cells found in younger mice. In
fact, some of the treated 11-month-old mice actually had fewer
oxidative scars than untreated eight-month-olds.
That, Baudry says, suggests that the compounds may not only prevent
damage, but may actually reverse prior damage to brain proteins. For
his next step, Baudry will investigate these and similar compounds in
younger and older mice, investigating how they affect memory, learning
and other brain functions as well as longevity.
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