Russian scientists have created a model of the biochemical process that occurs in brain cells at the initial stages of the development of senile dementia. The experiment confirmed the theory that the cause of age-related disorders is the action of free radicals in nerve cells. Developments will make it possible to diagnose such pathologies as Alzheimer’s and Parkinson’s diseases at an early stage. It is already possible to test drugs for age-related brain diseases on the proposed model. The results of research supported by grants from the Russian Science Foundation (RSF) are published in the journal Redox Biology.
Approximately 50 million people worldwide suffer from senile dementia. In 1% of cases, doctors note a hereditary predisposition to the disease. But it is still unknown what exactly triggers the process of destruction of nerve cells in the vast majority of cases and why some people are more susceptible to it than others. In addition, age-related mental disorders are usually diagnosed after the age of 65, and it is difficult to recognize the development of dementia at an earlier age. At the same time, scientists have long discovered that the first signs of the disease, such as a decrease in memory and learning ability, are accompanied by oxidative stress in brain cells. It occurs when the amount of antioxidant enzymes decreases in an aging organism and an excess of free radicals is formed – reactive oxygen species that react with the molecules of a living cell, destroying it. Until now, it has remained unclear whether this is the cause of diseases, their symptom or comorbidity. The study of the issue was hampered by the impossibility of directly observing and controlling the chemical processes occurring in the living brain.
A group of scientists at the Institute of Bioorganic Chemistry named after M.M. Shemyakin and Yu.A. Ovchinnikova of the Russian Academy of Sciences (Moscow) recreated controlled oxidative stress in individual mouse brain cells. For this, an artificial virus was created, which acts as a carrier of a special genetic construct. It provides neurons with a program written in DNA, thanks to which the enzyme D-amino acid oxidase is produced in viruses. On artificially grown neurons infected with the virus, scientists tested that adding D-norvaline to them causes the release of hydrogen peroxide, the longest-lived reactive oxygen species molecule in the cell. The virus was then injected into the hippocampus of laboratory mice using a microsyringe to find out what changes oxidative stress causes in the living brain.
Two weeks later, brain sections 300 µm thick were taken from virus-infected animals. Analysis of the samples included microscopic examination and electrophysiological experiments: the scientists induced oxidative stress in a particular neuron and recorded the electrical activity of that neuron. In all cases, there was a decrease in synaptic plasticity – the ability of nerve cells to strengthen or weaken the connection between neurons and regulate the rate of transmission of nerve impulses. Scientists associate this property of cells with the ability of mammals to learn and remember.
The model of the development of dementia at the cell level was built by scientists for the first time and allows you to determine the signs of the disease at an early stage. In the future, this will help diagnose mental degeneration at the very beginning, when the patient has not yet manifested cognitive impairment.
“What we have done on brain slices is a ready-made platform for testing drugs that would improve the function of nerve cells under conditions of oxidative stress. The next step is to obtain evidence that this process in brain cells leads to the development of Alzheimer’s disease. To do this, we will observe animals to understand how their cognitive functions change after exposure to our instrument,” says Oleg Podgorny, Candidate of Biological Sciences, Senior Researcher at the Institute of Bioorganic Chemistry, Russian Academy of Sciences.
