May 1, 2001 COLLEGE STATION - Texas A&M University biologists are studying the genetics of learning and memory in humans, which could help understand aging and help find cures for neurodegenerative diseases such as Parkinson's and Alzheimer's diseases.
Efthimios M. Skoulakis, who specializes in the molecular biology of learning and memory, is studying how oncogenes, the genes usually responsible for cancer, can also participate in normal learning processes. His work has been supported by grants from the National Science Foundation and the National Institute of Mental Health.
"Biologists usually thought that oncogenes are used either in the initial development of an individual, or are activated later, causing cancer in adults," Skoulakis says. "Now these oncogenes may also be active in the brain during normal adult life.
"One of the ways drug companies are combating cancer is to simply block the action of specific oncogenes to kill the tumors," he adds. "So if these genes have a good function in the brain, are we also going to stop certain brain functions?"
Skoulakis, an assistant professor of biology at Texas A&M, noticed that when some kinds of genes, the 14-3-3 genes, are turned off, flies have learning deficiencies, suggesting that 14-3-3 genes may regulate the oncogene activity of learning.
Flies have two different 14-3-3 genes, while nine of them have been identified in humans.
"We would like to understand why humans have so many 14-3-3 genes, how each of them function differently, or perhaps find out that they all function in the same way," Skoulakis says.
Scientists already know that most - but not all - of human 14-3-3 genes are expressed in the human brain. Skoulakis and his collaborators now want to know whether and which of these genes are involved in human learning.
To find out, the scientists used flies stripped of their own 14-3-3 genes, and they inserted one of the human 14-3-3 genes in the flies.
The flies are clones of each other and are raised in the same environment, so the only difference between a normal fly and a fly with a human 14-3-3 gene is that single gene, Skoulakis explains.
The gene can be turned on and off with heat shocks. It is activated between 25 and 27 degrees Celsius and deactivated below 25 degrees Celsius.
To compare fly learning abilities when the human 14-3-3 gene is either activated or deactivated, flies are asked to perform two different tasks.
In the first task, flies are asked to recognize two smells. One smell is associated with an electric shock, the other not. While moving in a maze, a fly chooses its way according to what it smells. It needs to remember the smell not associated with the electric shock to follow the right path through the maze.
The second task is based on fly mating behaviors.
Female flies mate only once because they store enough sperm to use it for nearly all the rest of their life. After they have mated, female fruit flies chase away any male that tries to court them, and males learn not to court females that have chased them once. But males with impaired learning abilities keep courting females on and on.
The electric shock task measures whether a fly remembers the odor associated with the shock, while the courtship task looks at how males remember being rejected by females.
"We have studied one type of 14-3-3 genes, and shown that when we turn it on, flies recover their learning abilities," says Skoulakis. "We would like to pursue these experiments by inserting the other human 14-3-3 genes in the flies and see if these genes differ from each other."
Skoulakis says that his work could help understand the decline of learning capabilities of aging humans, and elaborate models on the role of 14-3-3 genes in neurodegenerative diseases.
"We are interested in the effects of pathological proteins in humans, such as those found in Alzheimer's or Parkinson's brains," he says. "We would like to see if these proteins have similar effects in the fly's brain, and if they do, to use the fly as a model to study the mechanisms of neurodegenerative diseases."
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