A pill for blood pressure... and senile senility

Each of us is periodically surprised to find an unfinished cup of coffee in the kitchen, from which he was distracted by a story broadcast on TV or a phone call. With age, such cases of forgetfulness become more frequent due to the deterioration of the ability to hold a thought in memory under the influence of distracting factors.

Researchers at Yale University, working under the leadership of Amy Arnsten, not only deciphered the molecular mechanisms underlying the aggravation of this type of forgetfulness in monkeys, but were also able to prevent its development by introducing a certain chemical compound into the animal brain. Moreover, clinical studies of a drug with the described effect are already being conducted at the university.

As part of their work, the scientists recorded the electrical activity of neurons in the prefrontal cortex, a region of the brain in which signs of aging are most clearly manifested in both humans and monkeys. This region is responsible for the most complex manifestations of cognitive function: short-term memory, the ability to perform several tasks simultaneously and suppress distracting stimuli.

Earlier studies have shown that the special organization of the neural circuits of this region ensures the maintenance of a constant level of activity necessary for the formation of short-term memory. In other words, through mutual excitation, the neurons of the prefrontal cortex retain information in memory that no longer comes from the outside.

An analysis of the activity of neurons in the prefrontal cortex of young, middle-aged and elderly monkeys showed that the rate of formation of nerve impulses by cells of this region decreases over time. At the same time, other neurons, including those responsible for registering environmental stimuli, do not decrease the rate of pulse emission with age.

Researchers believe that the reason for this is a violation of the course of stress reactions. Under the influence of stress in the cells of the prefrontal cortex, including young animals, the concentration of the signaling compound cyclic adenosine monophosphate (cAMP) significantly increases, suppressing their activity by blocking potassium channels. (Arnsten suggested that this is a mechanism of evolutionary adaptation that allows the brain under stress to quickly transfer control from the "slow and thoughtful" prefrontal cortex to more primitive regions.) Under normal conditions, enzymes suppress the stress response and the brain returns to normal operation. However, apparently, the process of normal aging is accompanied by disturbances in the regulation of stress reactions.

The introduction of a drug blocking potassium channels into the brain tissue increased the rate of formation of nerve impulses by cells of the prefrontal cortex of old monkeys to the level of young animals.

Currently, Yale University is conducting clinical studies of the drug guanfacine, originally intended for the treatment of hypertension, the primary results of which indicate that its systemic administration helps to reduce the symptoms of age-related disorders of short-term memory. Therefore, the results obtained in animal experiments were not unexpected for researchers.

Understanding the mechanism of action of the drug will allow us to develop more effective and causing fewer adverse reactions analogues. Guanfacine can have a sedative effect and, in order to avoid this effect, patients have to undergo a slow process of getting used to the drug by gradually increasing the dose.

To date, it is unclear whether the effect of guanfacine extends to more serious memory and brain changes associated with Alzheimer's disease and other types of dementia. (Monkeys do not have Alzheimer's disease, so the analyzed memory disorders are obviously manifestations of the normal aging process.) However, researchers believe that the changes they observe occurring at the cellular level may increase the risk of developing Alzheimer's disease. Currently, they have already started work, the purpose of which is to study the feasibility of using the mechanisms they discovered in the early stages of this disease.

Article by Min Wang et al. The neuronal basis of age-related working memory decline was published on July 27 in the preliminary on-line version of the journal Nature.

Evgeniya Ryabtseva
Portal "Eternal youth" www.vechnayamolodost.ru based on Technology Review: Age-Related Memory Loss Reversed in Monkeys.

28.07.2011