"What I thought was happening was that our animals were having chronically high levels of GABA because they had lost their circadian rhythm," Ruby said. "So instead of rhythmic GABA, it is just constant GABA output."
To test that idea, Ruby and his colleagues gave the circadian-deficient hamsters a GABA antagonist called pentylenetetrazole, or PTZ, which blocks GABA from binding to synapses, thereby allowing the synapses to continue firing and keeping the brain in a more excited state. It worked. The learning-impaired hamsters caught up with their intact peers to exhibit the same level of learning retention.
Research on people with Down syndrome has shown that one reason they don't perform well on cognitive tests is that they grow up with what amounts to an over-inhibited brain. Studies on mice that exhibit symptoms of Down syndrome have demonstrated that when given PTZ, the mice demonstrate improved learning and memory. That research, conducted by Fabian Fernandez, then a graduate student in the lab of Craig Garner, a professor of psychiatry and behavioral sciences at Stanford, prompted Ruby to investigate whether using PTZ to reduce GABA levels would improve memory function in the hamsters.
Other researchers working with mouse models of Alzheimer's disease have reported similar findings. When those mice were given GABA antagonists, their ability to learn was restored, suggesting a possible link with their circadian system.
Ruby's findings may also have implications for the decline in memory function that older adults in general experience.
"In aging humans, one of the big things that happens is the circadian system starts to degrade and break down," Ruby said. "When you get older, of course, a lot of things break down, but if the circadian system is a player in memory function, it might be that the degradation of circadian rhythms
|Contact: Louis Bergeron|