CREB and Knockout Mice
A memory trace is solidified if there is a small gap in time between the pieces of information that need to be remembered. Using this technique, which is called spaced training, scientists engineered a fruit fly to have a photographic memory. In the same fruit fly species, they triggered a master gene called CREB, which has the ability to goad a number of other genes into action. In this manner, the fruit fly with a fabulous memory was born. Ideally, if we could stimulate CREB in the same way in
the human brain, total recall would become the standard for everyone. But there is no known method to turn a gene on or off in the human brain, so even though we all possess CREB, we don’t yet know how to galvanize it into action in people. The goal of these researchers is to see if manipulating CREB in some fashion will make it possible to unlock the full power of human memory.
Other researchers like Eric Kandel approach the same problem from a different angle. He takes mice and removes, or knocks out, a gene or set of genes that are involved in cognitive processes. These “knockout” mice perform horribly in mazes and similar tests of cognitive ability. Drugs are then administered, one by one, to see if they can reverse this glaring memory deficit in the knockout mice. One such promising agent is rolipram, but as yet there are no worthwhile clinical studies with
this compound. Another strategy is to block the synthesis of specific proteins by genetic manipulation, which then leads to memory loss in rats. As with the knockout mice, specific drugs can be given to reverse this process and correct the memory deficit. Kandel, in his dynamic way, has formed his own company to employ these techniques to try and find the magic pill that will reverse memory loss.
Other Novel Strategies
AMPA receptors are present throughout the brain, and are involved in synaptic connections between brain cells. These AMPA receptors play a role in boosting both learning and memory, and ampakines are substances that amplify or enhance these signals. Some investigators are trying to develop drugs that can amplify the AMPA signal, while others believe that this is a waste of time because ampakines share many similarities to caffeine, which improves attention and mental arousal with no direct impact on memory.
In animal models, a number of other substances can amplify long-term potentiation, which is the physiologic property of cells to remain depolarized, or stimulated, for an extended period of time. Kandel and other researchers believe that at the cellular level, long-term potentiation is the method by which a memory trace becomes solidified and is eventually transferred into long-term memory storage. A number of chemicals can amplify the effects of long-term potentiation. These include substances that stimulate dopamine receptors and others that inhibit the enzyme phosphodiesterase. In animal studies, these chemical substances improve transfer of information from short- to longterm storage. But as of yet, there are no clinical studies to back up these intriguing laboratory findings.
Earlier, I referred to Dennis Choi’s work on zinc and memory. Although few other researchers are putting much time and energy into studying metallic elements that are known to be involved in essential enzyme pathways, my guess is that this will change in the future. Sophisticated new technologies will help us to decipher what exactly these trace metals like chromium and selenium are doing in the brain. Future therapies may be based on increasing or decreasing the levels of these
metallic elements in a targeted fashion, taking into account the delicate balance that exists between these metallic elements and a variety of processes in the brain.
The elusive prion, discovered by Nobel laureate Stanley Prusiner, must not be forgotten. These microscopic prions play a role not only in neurological disorders, but possibly in memory loss due to the aging process itself. I suspect that we will hear a lot more about the role of prions in memory loss.
Taken From: The Memory Program How to Prevent Memory Loss
and Enhance Memory Power
