Is Old Age Memory Decline Reversible?

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Scientific American

January 31, 2008

 

Is Old Age Memory Decline Reversible?

New research suggests that triggering new nerve cell production in

adult brains could stave off short-term forgetfulness

By Nikhil Swaminathan

 

Scientists have found that a lessened supply of new nerve cells in

the adult brain apparently triggers short-term memory loss typically

associated with aging, setting the stage for one day developing

therapies designed to maintain a steady supply of fresh neurons to

keep the mind sharp.

 

" Neurogenesis (nerve-cell production) goes down with age … it's known

that with old age there's a decrease in short- term memory, " says

Ronald Evans, a genetics professor at the Salk Institute for

Biological Studies in La Jolla, Calif. " We know that if we can

increase the process, we know what the consequence could be in the

brain, which would be to increase short-term learning and memory. "

 

" New experiences, new memories [and] new learning [are] greatly

facilitated by neurogenesis, " he adds. " Neurogenesis is in fact a

fundamental feature of learning and memory. … Neurogenesis goes down

with age; and, it's known that with old age there's a decrease in

short-term memory. "

 

Evans is co-author of a study published in Nature that shows impaired

short-term memory and learning in adult mice, in which scientists

blocked the process of neurogenesis. They did this by engineering

mice that lacked one copy of the gene responsible for the production

of Tlx, a protein that the team had previously determined was crucial

to maintaining and renewing the arsenal of neural stem cells.

 

" The other allele (gene copy) is normal, but it is susceptible to

knockout upon ingestion of [the] orally active estrogen antagonist "

tamoxifen, Evans says. " It's a very effective knockdown. " After being

given tamoxifen (perhaps best known as a breast cancer drug) for

eight days, an otherwise normally developing mouse had more than 80

percent fewer new neural stem cells in its hippocampus (a structure

in the brain's frontal region linked to short-term memory).

 

The genetically altered mice performed as well as normal peers did in

experiments based on learning out of fear, such as associating a

sound or light flash with a shock to a paw. They failed, however, to

perform up to speed on a spatial memory task: It took days for the

mice lacking new nerve cells to lessen the time it took for them to

find a platform floating in a pool of opaque liquid on which they

could stand.

 

Normal mice took about three days to make the connection, but Evans

says the knockout mice were still on " a learning curve " six days into

the experiment. " They eventually learn, " he says, " but it takes them

much longer. "

 

Martin Wojtowicz, a physiologist at the University of Toronto,

downplayed the finding, noting that it contradicts his own research

on rats, which found a link between neurogenesis and fear, but not

memory. " They see a very subtle effect in the water maze, " he

says, " but other than that, nothing. "

 

Evans, however, sticks by the team's conclusions, pointing out that

Nature required several additional tests be conducted to verify the

data. He also notes that in previous studies, researchers irradiated

parts of the animals' brains or injected them with cancer drugs that

destroyed more than targeted nerve cells, making it difficult to

determine whether it was the suspect cells or other damaged areas

that were to blame for certain behaviors. In contrast, he says, his

team explicitly links neurogenesis to short-term memory, which in the

future could lead to a drug designed to stimulate nerve cell

production and potentially counter memory loss in older adults.