Word: receptor
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Dates: during 1990-1999
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...that's just what Tsien & Co. did, focusing not just on the NMDA receptor but on a particular component of it. Called NR2B, it's very active in young animals (which happen to be good at learning), less active in adults (who aren't), and is found mostly in the forebrain and hippocampus (where explicit, long-term memories are formed). The researchers spliced the gene that creates NR2B into the DNA of ordinary mouse embryos to create the strain they called Doogie. Then they ran the mice through a series of standardized tests--sort of a rodent...
...altered mice grow up looking and acting just like ordinary mice, with no evidence of seizures or convulsions, according to Tsien. That's critical. The NMDA receptor shows up throughout the brain, and though calcium is crucial to learning and memory, too much of it can lead to cell death. That's what happens during a stroke: when brain cells are deprived of oxygen, they release huge amounts of glutamate, which overstimulates nearby NMDA receptors and kills their host cells. Nature may have designed NR2B-based receptors to taper off in adult brains for a reason. Some scientists fear that...
Premature cell death isn't the only possible complication. Stanford's Robert Malenka has shown that the NMDA receptor is involved in sensitizing the brain to drugs like cocaine, heroin and amphetamines, and others are investigating its role in triggering chronic pain--two more indications that it may not be wise to try to fool Mother Nature...
...will be a while before such dangers arise, though, and--as cancer researchers have discovered all too often--it isn't even certain that what works in mice will work in people. Tsien and his colleagues believe it's not unreasonable to think it will. "The NMDA receptor in humans is nearly identical to the receptor in mice, rats, cats and other animals," he says. "We believe it's highly likely that it plays a similar role in humans...
...ranging from estrogen replacement (which may promote the growth of some neurons) to entirely new drugs are at various stages of development. In the near future, two new cholinesterase inhibitors, ENA 713 (Exelon) and metrifonate, are expected to become available. Memory researchers have also been looking at the NMDA receptor, target of the Princeton experiment. But tests of possible drugs to enhance memory have been inconclusive. Says Bill Thies, vice president for medical and scientific affairs at the Alzheimer's Association: "I think in a 10-year window we'll see some revolutionary stuff to prevent the disease...