Boosting Cognition in Down Syndrome
By Greg
Miller
ScienceNOW Daily News
18 November 2009
Boosting the
level of a brain chemical reverses learning impairments in a mouse model of
Down syndrome, researchers report. The work adds to emerging evidence that
cognition-enhancing drugs may one day help humans with Down syndrome lead more
independent lives.
Down
syndrome is the most common cause of mental retardation, affecting
approximately one in 800 babies at birth. People with the disorder have an
extra copy of chromosome 21, giving them additional copies of hundreds of
genes. This somehow alters brain development and causes mild to severe learning
disabilities.
To
investigate what goes wrong in the brain of someone who has Down syndrome,
researchers led by neurobiologist Ahmad Salehi of Stanford University in Palo
Alto, California, turned to a genetically modified strain of mice that has
three copies of more than 100 of the genes found on human chromosome 21. These
so-called Ts65Dn mice exhibit learning and memory deficiencies and other
symptoms of Down syndrome. When Salehi and colleagues examined the brains of
Ts65Dn mice under a microscope, they discovered degeneration in a region near
the base of the brain called the locus coeruleus. This region contains neurons
that extend armlike axons all the way to the hippocampus, a key memory center
tucked deep inside the temporal lobes. These neurons release the
neurotransmitter norepinephrine, which promotes learning and memory in the
hippocampus.
Reasoning
that the loss of the locus coeruleus neurons might undermine learning and
memory by causing a deficit of norepinephrine in the hippocampus, the
researchers gave Ts65Dn mice drugs that boost levels of this neurotransmitter
throughout the brain. A few hours after delivering the drugs, the researchers
tested how well mice were able to learn and remember an enclosure in which
they'd received a mild electric shock. Without the drug, Ts65Dn mice performed
miserably on this memory test, but with the drug they were as good as normal
mice, the researchers report today in Science Translational
Medicine.
Because
this type of learning depends on the hippocampus, the findings suggest that's
where the norepinephrine boost exerts its beneficial effect, Salehi says.
Several drugs that enhance norepinephrine are already approved or are in
advanced clinical trials for treating low blood pressure and other disorders in
humans, which should make it easier to launch a trial in people with Down
syndrome if additional animal studies support that approach, Salehi says.
"It's
a very positive development," says Roger Reeves, a geneticist at