by Nicolas Posunko,Skolkovo Institute of Science and Technology

Time takes its toll: Without refrigeration, it is only a matter of time before molecules in a dead brain undergo natural transformations obscuring the effects of disease. Credit: AI generators Gemini and Deep Dream Generator

Skoltech researchers have investigated the way the composition of small molecules called lipids and metabolites varies in the brain in the first hours and days after death.

Looking at samples from humans, mice, and rats, the study considered the levels of nearly 1,000small molecules. By showing most of them to be fairly stable over the first 48 hours and documenting the transformations undergone by the rest, the work opens the way for further research that could establish the brain-based molecular footprint ofschizophrenia,major depressive disorder, and other mental and neurological disorders, whose underlying biology remains poorly understood.

This research waspublishedin the journalBiomolecules.

"Consider schizophrenia: We actually don't know as much about its causes, the affected brain regions, and themolecular changesinvolved, with obvious repercussions for both diagnosis and treatment," said the lead author of the study, Marina Zavolskova, a research intern and a Ph.D. student of the Life Sciences program at Skoltech.

"To truly understand this and other disorders, people are looking into the differences, say, inprotein levelsbetween the healthy and the pathological brain."

"Lipids and metabolites, too, could be of use," she goes on. "For example, our colleagues recentlyreportedheadway in measuring thelipidlevels in the blood of patients with schizophrenia and depression, but analyzingbrain tissueis more challenging, because you only get the sample after the death of a patient, and you never know which of the observed effects are due to the disease and which are due to tissue decay. Well, you do know the latter now."

Experiment outline: Brain tissue samples from three species at various stages of degradation between zero hours and 48 hours from death are analyzed via an advanced form of mass spectrometry (UPLC-MS/MS), measuring the distributions of small molecules present in the samples. Credit: Marina Zavolskova et al./Biomolecules

While the study only looks at healthy brains, it establishes a baseline to calibrate the future data from both pathological and healthy brains for their comparison.

The team documented the degradation trends for each of the three species, including humans, for 971 small molecules, whose levels were monitored at death, 48 hours later, and five more times in between.

The abundance levels of 77% of the 867 studied lipids and 25% of the 104 studied metabolites were not significantly affected by the two-day delay without sample refrigeration.

The natural decay of the rest of them can be accounted for in future studies investigating the molecular underpinnings of schizophrenia, major depressive disorder, and other conditions by introducing the appropriate corrections based on the team's findings.

More information: Marina Zavolskova et al, Postmortem Stability Analysis of Lipids and Polar Metabolites in Human, Rat, and Mouse Brains, Biomolecules (2025). DOI: 10.3390/biom15091288

Provided by Skolkovo Institute of Science and Technology