Millions of chemical reactions occur in our brains every second, unnoticed until their delicate balance is disrupted.
Metabolome is the complete set of all small molecules in an organism, organ, or individual cell. If we imagine our body as a huge chemical plant, then the metabolome is all the intermediate products and final output of this plant. This includes amino acids, sugars, organic acids, lipids, and many other compounds with a molecular weight of less than 1 kDa .
For many years, it was believed that the brain feeds exclusively on glucose. Indeed, glucose remains the main energy substrate for the brain, and its transport across the blood-brain barrier is ensured by special transporter proteins GLUT1 and GLUT3 2 . However, modern research has shown that the picture is much more complex.
Primary energy source
Process glucose
Energy for neurons
One of the most striking discoveries in recent years has been the discovery of a close connection between metabolic processes and cognitive functions. Research by Tingley and colleagues, published in Nature in 2021, showed that sharp wave ripples in the hippocampus - a region of the brain critical for memory - are accompanied by a decrease in blood glucose levels approximately 10 minutes after their occurrence 7 .
Sharp wave ripples in the hippocampus are associated with memory consolidation.
Blood glucose levels decrease following hippocampal activity, showing brain-body communication.
This discovery testifies to the existence of a complex feedback system that allows the brain not only to consume energy but also to actively participate in regulating its distribution in the body. Thus, the brain metabolome acts as a connecting link between thought processes and the body's overall energy metabolism.
Aging brings significant changes to the brain metabolome. A 2021 study in which scientists analyzed 1547 metabolites in ten regions of the brains of mice of different ages revealed the following patterns 6 :
Differences in the metabolome between different brain regions decrease with age.
Sphingolipids increase in the adult brain and decrease in old age, leading to myelin loss.
Concentration of key neurotransmitters decreases in the aging brain.
| Type of Compounds | Nature of Changes | Consequences for Brain Function |
|---|---|---|
| Sphingolipids | Decrease in quantity and structural changes | Impairment of nerve impulse transmission |
| Neurotransmitters | Decrease in concentration | Worsening communication between neurons |
| Proteins and Amino Acids | Activation of breakdown | Loss of neuronal mass |
| Energy Substrates | Reduced utilization efficiency | Worsening energy supply to neurons |
Research shows that disturbances in the brain metabolome underlie many neurological and mental illnesses.
In vascular brain diseases, ischemia triggers a cascade of pathological reactions leading to severe disturbances in neuronal metabolism. Interestingly, these disorders have different features in middle-aged and elderly patients: in younger patients, hemodynamic changes predominate, while in the elderly - metabolic changes 1 .
In mild and moderate cognitive impairments, organic brain damage is often not detected, but significant changes in neurometabolism are revealed. These changes can manifest as a shift in the acid-base balance towards acidosis or alkalosis, which accordingly requires different therapeutic approaches 4 .
| Pathological Condition | Key Metabolic Markers | Detection Methods |
|---|---|---|
| Acute Stroke Period | Increased lactate, decreased N-acetylaspartate | Magnetic Resonance Spectroscopy |
| Cognitive Disorders | Shift in acid-base balance, decreased energy metabolism | Neuroenergocartography |
| Neurodegenerative Diseases | Impaired glucose utilization, oxidative stress | PET, Mass Spectrometry |
Modern science has a powerful arsenal for studying the brain metabolome:
A highly sensitive method that allows registering hundreds or even thousands of metabolites in a single measurement .
A less sensitive but more reliable quantitative method, ideal for measuring absolute concentrations of compounds .
Used in clinical practice to assess the content of key metabolites in various brain regions 1 .
| Metabolite | Normal Function | Changes in Pathology |
|---|---|---|
| N-acetylaspartate | Marker of healthy neurons | Decrease in neurodegeneration and ischemia |
| Choline | Component of cell membranes | Increase in gliosis and enhanced membrane breakdown |
| Lactate | Product of anaerobic glycolysis | Increase in ischemia and hypoxia |
| Creatine | Buffer of energy metabolism | Decrease in impaired energy metabolism |
Studying the brain metabolome opens new horizons in the diagnosis and treatment of neurological diseases. Today, metabolomic analysis already allows:
Identify diseases when structural changes have not yet occurred but metabolic shifts are already evident.
Develop personalized treatment regimens based on individual metabolic profiles.
Create new neuroprotective strategies aimed at correcting specific metabolic disorders.
Understand the deepest mechanisms of our brain's work and find keys to treating currently incurable diseases.
The brain metabolome represents a dynamic reflection of the most complex biochemical processes underlying our ability to think, feel, and remember.
From energy metabolism providing the basic needs of neurons to the fine-tuning of neurotransmitter systems - all aspects of brain function are reflected in its metabolome.
Studying this "chemical soul" of the brain not only expands our fundamental knowledge but also opens new paths for solving practical medical problems - from early diagnosis to the development of fundamentally new treatment methods.