Fat itself: a lipid map will help scientists in the fight against brain diseases

Russian scientists have developed a map of the fat content of the human brain, indicating the concentration of lipids in its different areas. In the future, it will make it possible to more accurately select therapies for the treatment of mental illnesses, such as schizophrenia or Alzheimer's disease. Izvestia got acquainted with the interim research results and scientific plans.

Cards on the table

Maria Osetrova, a research engineer at the Vladimir Zelman Center for Neurobiology and Neurorehabilitation, and her colleagues have found a way to fix and indicate the location of lipids, organic fats, a structural part of the cell membranes of the central nervous system (CNS).

— In total, more than 400 different lipids were found. We noticed that almost all of them, that is, more than 90%, were distributed unevenly between parts of the human brain. High cholesterol levels were recorded in the part of the brain responsible for movement and in the visual cortex, but in the prefrontal cortex, located in the frontal lobe and providing decision—making, cholesterol was lower, says Maria Osetrova.

Photo: IZVESTIA/Pavel Volkov

The human brain contains a lot of lipids, and their functions are extensive. For example, they supply energy to cellular processes, form cell membranes, and participate in intercellular and intracellular communication. Myelin is especially rich in lipids, a substance that surrounds the axons of nerve cells, protects them from external influences and increases the speed of electrical impulses along the axon. Due to myelin and lipids, the axon looks like an insulated electrical wire and quickly transmits electrical impulses through synaptic channels (the distance between neural networks).

Photo: Global Look Press/Vadim Akhmetov

Lipids are involved in both neurogenesis and impulse transmission. Each variety has its own function, lipid metabolism in the brain is closely related to energy processes in it, oxidative stress, neuroinflammation and aging, scientists explain.

— For example, cholesterol in the brain is mainly contained in the myelin sheaths, the need for it appears to restore the processes of neurons after nerve damage. Fatty acids can enter the brain and undergo oxidative degradation, and when there is a shortage of nutrients, the cellular energy source switches from glucose metabolism to fatty acid oxidation, says MD, Professor at the Volga Region Research Medical University (PIMU) Irina Mukhina.

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The cause of schizophrenia?

The functions of lipids and, most importantly, their effect on neurogenesis have not yet been thoroughly studied. However, scientists believe that impaired lipid metabolism in the brain may underlie a wide range of diseases of the brain and the nervous system, such as schizophrenia and autism or bipolar disorder. In schizophrenia, the concentration of certain lipids and myelin in the brain is lowered, and in autism, on the contrary, it can be increased. These deviations can lead to impaired conduction between brain regions and imbalance of information processing by neural networks, pathology of the functions of the white matter of the brain, scientists believe.

— The metabolism of lipids in the brain must be balanced for its active functioning and our cognitive longevity. Excessive stress, leading to excessive activation of neurons, lipid peroxidation, will disrupt the lipid balance, which can lead to excessive accumulation of lipid droplets in the brain and trigger pathological processes leading to dementia and early aging, says Dr. M.N., Professor of the Volga Research Medical University (PIMU) Irina Mukhina.

Photo: IZVESTIA/Andrey Erstrem

To determine the relationship between brain morbidity and lipid concentration and to reproduce aspects of various human neurological and psychiatric diseases in animals, Russian scientists from the Laboratory of Cognitive Dysfunctions of the Federal State Budgetary Institution of the Russian Academy of Sciences and the Department of Normal Physiology at Sechenov University are conducting laboratory research on genetically modified mice. Their genes, scientists say, are already known for their role in various human diseases. In the laboratory, they are artificially removed from the genome in a complex and multi-step procedure.

— A gene is removed from the cells of a healthy mouse, and such a cell is implanted by artificial insemination. If everything goes well, then the descendants of this animal have signs of a disease that needs to be studied. These signs are different. For example, if scientists reproduce Alzheimer's disease, then we are talking about the formation of amyloid plaques and memory impairment. If they simulate human symptoms of depression, they observe in mice a decrease in sensitivity to pleasure, for example, a decrease in pleasure from sweets. When mice get regular water and slightly sweetened water to choose from after stress, in case of stress resistance, animals will prefer sweet water, and if there are signs of depression, then we see a decrease in interest in sweet water. The ultimate goal of our work is to deepen understanding of the nature of human neurological and psychiatric diseases in order to optimize their treatment," says Tatiana Strekalova, Head of the NIOPP Cognitive Dysfunction Laboratory, Professor at the Department of Normal Physiology at Sechenov University.

Photo: Global Look Press/Friso Gentsch

Lipids and boundaries

The map of lipids in the brain is an intermediate result of basic research. So far, scientists cannot answer exactly how to select a therapy for the treatment of brain diseases — this will take years of research. After all, the brain is a very autonomous system that protects its habitual working mechanisms. In particular, when choosing therapy for a particular disease, it will be necessary to take into account the presence of a blood—brain barrier - a border of a very dense layer of impenetrable endothelial cells that supports the homeostasis of the brain and protects it from ingestion of toxic substances from the blood and new drugs.

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— Following the creation of the lipid map, we plan to observe the genetic influence of certain proteins on lipids, as well as on brain diseases, so that the picture of the study would be more voluminous. So the main experiments are still ahead. We will study how much the lipid composition of the brain differs between healthy people and people with different diagnoses, which regions accumulate the most differences, and which compounds behave most contrastingly," sums up Maria Osetrova.