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Brain Viagra - Part 2 (video)
April 21, 2003

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Interviewee: Josh Dubnau, Cold Spring Harbor Laboratory; Dr. Daniel Alkon, Blanchette Rockefeller Neurosciences Institute.

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Scientists Switch Memory Recall On and Off in Fruit Flies - CSHL

Memory enhancement: the search for mechanism-based drugs - Nature

There’s a huge market for substances that claim to boost memory, but when can we expect drugs designed and proven to do that?

As this ScienCentral News video reports, advances in genetics research may be helping to make effective memory drugs a reality.

Shocking Fruit Flies

Most animals have the ability to remember past experiences. So scientists are studying how they learn and remember things, in order to ultimately make drugs that can enhance human memory.

“We now know from the work of many different labs that the genes involved in different aspects of learning and memory are the same genes in fruit flies, in marine invertebrates, in mice and rats, and most certainly in humans,” says Josh Dubnau, assistant professor at Cold Spring Harbor Laboratory.

Dubnau, along with Tim Tully, taught fruit flies, each one genetically engineered to lack a different gene, to associate an odor in a tube with an electric shock. “We give them a little foot shock whenever they smell one odor,” explains Dubnau, “and they can learn that that odor predicts something nasty, a foot shock, and in the future they will avoid that odor if given the opportunity.”

Nearly all 6,000 flies in the experiment learned to avoid that smelly tube. If one of the flies did not learn to avoid the shocking odor, the researchers figured the gene it was missing must be important to memory.
Dubnau also used high-tech “gene chips”—which can quickly determine which genes are active, or “turned on” in an animal while it is performing a certain task—to find more genes that were active in the fruit flies during learning and memory. As Tully and Dubnau reported in the journal Current Biology, all told they were able to find a total of 92 such “memory genes.”

“We can now take each one of these genes that we’ve identified and use the tool box of techniques that is available in order to try and understand how these genes function during memory formation,” says Dubnau.

Rats Studied Too

Daniel Alkon, a biophysics research professor at the Blanchette Rockefeller Neurosciences Institute, studied the memory genes of rats. The rodents were first were trained in the Morris Water Maze wherein the rat has to find a platform submerged in a tub of water. After several trials, the rat learns to find the platform very quickly. Then Alkon used gene chips to analyze the gene activity in tissue samples from the rats, to see which genes among thousands were active during the learning process. Using the gene chips, Alkon found 140 genes that he considered crucial to learning and memory. But there was more.

“Even though we did see many [genes] that changed in different periods,” says Alkon, “we only saw one that changed consistently throughout the entire process. And that was a gene that codes for a protein called the ‘fibroblast growth factor’.”

Since this one protein was changing throughout the rats’ entire learning and memory process, Alkon and his team wanted to see if it had a direct effect on memory. They injected this protein into rats’ brains, and then put them back into the Morris Water Maze. They reported in the Proceedings of the National Academy of Science, that the rats that had been injected with the protein doubled their retention of where the submerged platform was—their memories were twice as sharp as the memories of rats that were not injected with the protein.

“That approach—from gene, to protein, to drug for the protein—represents a kind of paradigm that may be valuable for a variety of cognitive disorders in the 21st century,” says Alkon.

Both Dubnau’s and Alkon’s research offer new avenues to explore in the quest for a memory drug for humans, which would help millions, especially the aging. “There are many types of age-related changes that people don’t like, that affect the way we function, and that people think nothing about doing something about,” says Steven Ferris of the Institute for Aging & Dementia at NYU Medical School. “We have drugs to stop hair loss. Everyone over a certain age wears glasses that allow you to see print close up. Many people when they get older need hearing aids. There are many other treatments for a host of age-associated declines that people experience that we think nothing about doing something about. Why not do the same for memory?”

by Karen Lurie

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