Zavolskova Marina, Senko Dmitry, Bukato Olga, Troshin Sergey, Stekolshchikova Elena, Kachanovski Mark, Akulova Anna, Afonina Maria, Efimova Olga, Petrova Daria, Osetrova Maria, Khaitovich Philipp
Skolkovo Institute of Brain-Inspired Technologies, Bolshoy Boulevard, 30, Bld. 1, Moscow 121205, Russia.
Institute of Clinical Morphology and Digital Pathology, I.M. Sechenov First Moscow State Medical University, Abrikosovsky Lane, 1, Moscow 119435, Russia.
Biomolecules. 2025 Sep 5;15(9):1288. doi: 10.3390/biom15091288.
Lipids and polar metabolites are emerging as promising indicators of the brain's molecular phenotype in both clinical and fundamental research. However, the impact of postmortem delay on these compounds, unavoidable in human brain studies, remains insufficiently understood. In this study, we examined the postmortem stability of lipids and polar metabolites over a 48-h interval in the brains of three species: humans, rats, and mice. We show that the abundance levels of 23% of the 867 studied lipids and 75% of the 104 studied polar metabolites were affected significantly by postmortem delay in at least one species. The postmortem effects correlated positively and significantly among the species, while showing an approximately tenfold slower rate in humans compared to rodents. The only exception to the postmortem rates deceleration was a group of oxidized fatty acids, which accumulated at similar speed in both humans and rodents. These findings provide valuable insights for improving reproducibility and refining the interpretation of human and rodent brain lipidome and metabolome data in future studies.
在临床和基础研究中，脂质和极性代谢物正成为大脑分子表型的有前景的指标。然而，在人脑研究中不可避免的死后延迟对这些化合物的影响仍未得到充分理解。在本研究中，我们在人类、大鼠和小鼠三种物种的大脑中，于48小时的时间间隔内检测了脂质和极性代谢物的死后稳定性。我们发现，在至少一个物种中，所研究的867种脂质中的23%以及104种所研究的极性代谢物中的75%的丰度水平受到死后延迟的显著影响。物种之间的死后效应呈显著正相关，而与啮齿动物相比，人类的死后效应速率慢约十倍。死后速率减速的唯一例外是一组氧化脂肪酸，其在人类和啮齿动物中以相似的速度积累。这些发现为提高未来研究中人类和啮齿动物脑脂质组和代谢组数据的可重复性及完善其解释提供了有价值的见解。
