A new study by researchers in Italy and the United States has found 140 genes, located in an area of the brain called the hippocampus, that had significantly altered activity when rats navigate a water maze. By enhancing the protein product of one of those genes, the scientists significantly boosted the rodents' spatial learning ability.
Dr. Daniel Alkon, scientific director of the Blanchette Rockefeller Neurosciences Institute in Rockville, Md., and a co-author of the paper, said the work could one day help treat people with Alzheimer's disease.
"Alzheimer's disease at the beginning is a disease of memory. We expect that these genes [or their human counterparts] will also be important as early targets of Alzheimer's disease," he said.
A report on the findings appears this week in the Proceedings of the National Academy of Sciences.
Alkon and his colleagues used "gene chip" technology to watch the DNA of rat brains after the rodents performed a standardized behavior test called the Morris water maze. This activity is a well-established method of assessing spatial learning and memory, which are housed in the hippocampus.
They also studied rats that swam untested, as well as a group that simply hung around in their cages.
By analyzing cells in the hippocampus at various points in time, Alkon's team was able to compare the rats' gene activity and distill that attributable to learning.
"There are a certain number of genes that change just with physical activity, and they have an overlap with some genes that changed with learning," Alkon said.
The genes made the cut if their activity increased or decreased by at least a factor of two, and if that effect was reproducible, Alkon added. To confirm the results, the scientists also studied the proteins generated by the genes.
The researchers classified the 140 retention genes into six major families, the largest of which regulates signals between cells. One of these signals is mediated by a small protein, or peptide, called fibroblast growth factor (FGF)-18. In another experiment, Alkon's group showed that they could improve spatial learning in rats by injecting them with FGF-18.
Although the size of the effect was hard to quantify, Alkon said treated animals improved their performance in the water maze by about 30 to 40 percent.
"It was not a very small, minor change," he noted.
Michael Fanselow, a psychologist at the University of California at Los Angeles, who studies the biology of behavior, said uncovering gene expression in the brain is key to understanding memory.
But, he added, "people have to get beyond the notion that there's going to be a memory gene."
Instead, the process of building memories is a finely choreographed dance between many genes, some with activity rising and others falling quiet, he said.
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