Gene therapy: a new method of improving the ability to remember and learn.

Stanford University neuroscientists have created a gene capable of strengthening memory and the ability of animals to learn while undergoing stress.

In the article published in the November issue of the Journal of Neuroscience, the scientists said that the experimental technique could one day help create new forms of gene therapy that could diminish. Serious side effects of steroids, a drug prescribed by doctors for millions of patients with arthritis, asthma and other illnesses.

Morris Water Labyrinth Experiment
(Photo: ScienceDaily)

' Steroids can' disturb 'a part of the brain that functions in relation to judgment and perception ,' said Robert Sapolsky, a neurologist, one of the scientists involved in this study. know. ' In the worst cases, it is called steroid dementia. It is ideal to safely inject this new gene into your body, as it will protect you from some cognitive side effects while still allowing steroids to make good effects. most of the tasks it has to do with other parts of the body. '

Hormone-induced reactions.

In this research paper published in the Journal of Neuroscience, Mr. Sapolsky and his colleagues focused on the effects of stress on the hippocampus, the cortical region with selection and determination functions. , evaluate problems, so it is important for learning and for memorization.

Neurons in the hippocampus have many receptors and these receptors will respond to a group of steroid hormones called glucocorticoids, a substance secreted from the adrenal glands of male and female mice. times they are stressed.

When this large amount of corticosteroids bind to the receptors in the hippocampus, they can cause a series of harmful biochemical reactions, causing damage to nerve cells in the hippocampus brain area and eventually weakening memory and ability to learn.

But not all hormones are harmful. Estrogen, the most important female hormone, helps strengthen memory and therefore can prevent the negative effects of corticosteroids on awareness.

'Hormone Estrogen protects memory against stress,' said Andrea Nicholas, Stanford University postdoctoral fellow, a scientist who led the study. ' In women, the hormone estrogen in the brain has long-term protective effects for them. As people get older, women are generally healthier than men in terms of cognition, partly because they have the protection of hormones estrogen. "

Hippocampus (Photo: memorylossonline.)

In a 2004 study, Mr. Sapolsky and colleagues demonstrated that gene therapy can be used to neutralize the harmful effects of stress on laboratory mice. The goal behind gene therapy is to eventually cure the disease or cure the wound by injecting a useful gene into the patient's DNA. In the experiment, Mr. Sapolsky and his team created what geneticists call chimera - an experimental DNA strand made of two linked genes that in this experiment was a Gene glucocorticoid receptors from mice combined with estrogen receptor genes from humans.

When the new chimera gene was injected into the hippocampus region of the mouse, the results were impressive. This new gene produces new receptors that can quickly turn stress-induced glucocorticoids into beneficial estrogen signals.

Nicholas said: ' That experiment shows that gene therapy is effective at the molecular level. Later, we wanted to know whether the chimera gene actually changes the behavioral effects that we know are due to stress hormones caused by living mice. '

Water maze

To find out, Mrs. Nicholas and her colleagues set up a Morris Water Labyrinth experiment, an experiment widely used by neuroscientists to test the ability to remember space in mice. The maze of water consists of a circular lake about 5 feet wide and contains about 2 feet of water. A platform is placed just below the water surface. When an untrained mouse will swim around to find the exit until it discovers the platform and crawls out of the maze.

'When the mice were dropped into the labyrinth for the first time, they felt quite disoriented, ' said Nicholas. 'Usually they take about a minute to identify the platform, but over time, they are very adept at finding the platform. Once they know where it is, they will swim directly to that platform in about 5 to 10 seconds. After that, we took the platform back out of the labyrinth and watched what they did then. '

Steroid (Photo: answers.com)

A very important part of the water labyrinth experiment is counting the number of times a mouse swims around where the podium was first placed. ' That's how to measure their perseverance ,' explains Nicholas. ' If they knew the platform very well, they would just swim around where the platform was, as if to tell themselves,' Oh, I know the platform must be here. '

Stress test

The purpose of this study was to know whether mice treated with gene therapy were different from normal mice during the water labyrinth experiment after they underwent stress. To produce gene therapy, the scientists numbed the rodent, ' inserted ' the syringe into its hippocampu area and injected a genetically modified virus with DNA containing the chimera gene.

Once injected, the individual ' copies ' of the virus will attack the hippocampus neurons, thus ' delivering ' the chimera gene and activating it in the rat's brain. This new gene then converts harmful corticoids into beneficial estrogens - a process that could theoretically prevent the negative behavioral reactions of mice when stressed.

To ensure that natural estrogen is not an impact factor, this experiment was only performed on male rats. Each mouse is trained to find the hidden platform. To increase the amount of corticosteroids in their blood, scientists give mice a lot of stress, such as not allowing them to budge or to force them to take cold temperatures and then release them into the water, where they The scientist will calculate how much they swim to the area where the platform is hidden at a fast rate and how often.

Stress tests were performed before the mice were trained, right after training and 24 hours later. ' This takes advantage of three different areas and three different time periods - the impact of stress on learning, the accumulation of memory learning information and recalling those memorizing information, ' Mr. Sapolsky explained. And the results are clear: When mice undergo stress 24 hours after training, mice with chimera genes swim to the hidden podium area and take less time to find the platform. are normal mice.

Glucocorticoid (Photo: faculty.smu.edu)

Nicholas said: ' These results are quite amazing. They showed that this gene therapy not only prevented the harmful effects of glucocorticoids but also really strengthened the ability to remember space and learn through controlled situations of estrogen, even in presence. of stress . '

Gene therapy

Sapolsky said these findings also show the potential value of gene therapy for people who suffer severe cognitive side effects because of a large dose of corticosteroids to treat the disease. multiple sclerosis, rheumatoid arthritis and other diseases.

He explained: 'There is a high probability that gene therapy can be used to protect the brain when you have to go through a series of problems with a certain disease. Users who take high doses of these steroids may be clinically depressed. As a rule, you can also use gene therapy to protect those people. '

However, however, it was only until scientists determined how to safely inject the chimera gene into humans that the gene could be used in medicine. He also noted that this treatment should only be used to prevent neurological side effects caused by pharmaceuticals and should not be used by people who merely want to reinforce short-term memory ability (likely ability to remember things that happened briefly before) and their study skills. ' You can't' drill 'someone's head and inject a virus just because he or she is going to an important contest .'

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