Improving Learning and Memory in Rats under Stress Using Gene Therapy

Have you ever wished that there was a drug you could take during stressful situations to maintain your intellectual accuracy and awareness? Well now, according to several Stanford University neuroscientists, this idea may not be as far-fetched as originally assumed. In a recent article published on the Science Daily website entitled “Scientists use Gene Therapy to Improve Memory and Learning in Animals”
(http://www.sciencedaily.com/releases/2006/11/061108122235.htm), a specific gene was inserted into rat test subjects that proved to successfully improve both their learning and memory when faced with the negative hormonal impacts resulting from stress.

Throughout this study, the neuroendocrinologist, Robert Sapolsky, and his partners examined the effect of stress on the hippocampus, which is the part of the brain designated to learning and memory. The nerve cells that make up this part of the brain have receptors that are sensitive to particular types of steroid hormones, called glucocorticoids. When a male or female becomes stressed, these hormones are released into the bloodstream and become attached to the receptors in the hippocampus, contributing to the gradual destruction of its nerve cells. As a result, both memory and learning become weakened. Estrogen, however, is a known hormone that actually promotes memory in humans and is therefore believed by many scientists to counteract the negative impact that corticoids have on the brain.

In order to verify the beneficial impacts of estrogen on the brain during times of stress, the scientists in this article performed gene therapy on numerous laboratory rats. By artificially creating a strand of DNA composed of both a glucocorticoid-receptor gene from a rat and an estrogen-receptor gene from a human, the scientists were then able to inject the man-made gene, or “chimera”, into the hippocampus of the rat to observe its effects. As originally hoped, the gene proved to create new protein receptors that immediately transformed glucocorticoids (which promote stress) into estrogen signals (which protect the brain’s memory against stress). Having proved that gene therapy is successful at the molecular level, the scientists then wanted to see how the artificial gene would impact the behaviors of the rats during times of stress.

To determine this question, the scientists used a Morris Water Maze set-up, which is composed of a circular pool that is five feet wide and filled with two feet of water. Below the surface, there is a hidden platform exiting the water, which the rats are trained to find with repeated exposure. Once they have been trained to find it, the scientists will then remove the platform to measure how many times the rats will continue to swim over its previous location. This is a measure of the rats’ persistence. The goal of the scientists for this particular experiment was to see if the rats treated with the chimeric gene, mentioned previously, would perform differently than rats not treated with gene therapy when exposed to stress. The rats were subjected to such factors as cold temperatures in order to reach a stressful state and were given stress tests both before and after the experiment. As it turned out, the rats that were given the estrogen-induced gene swam to the area where the platform used to be faster, and donated more time looking for it than rats without the gene did.

The findings from this experiment are drastic. Not only do they imply that this form of gene therapy can successfully counteract the negative impacts of glucocorticoids on the brain, but they also show that it can improve spatial memory and learning in rats, even during times of stress. The scientists involved in this experiment are already focusing their findings on future implications. They hope that with further testing, similar forms of gene therapy can be used to promote brain activity in patients suffering from such diseases as multiple sclerosis, who must take large doses of corticoids, which in turn alter their learning and memory abilities drastically. Sapolsky and his partners are optimistic that one day, the negative cognitive side effects of stress can be prevented all together.

Additional Comments: In regards to certain comments made on this blog, I would like to add that no additional effects were noted by the researchers when observing the rats' behaviors. The males did not take on any evident feminine qualities as a result of the estrogen, even though this was not specifically tested for. Further research is being done by scientists to develop the findings of this experiment.

Posted by EJM (11)