Scientists uncover a hidden map of the brain with 539 distinct regions
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Researchers at EPFL have created what ScienceDaily described as a detailed map showing how lipids are distributed throughout the mouse brain, identifying 539 chemically distinct territories that the team named “lipizones.” The findings, which reveal what the outlet called a hidden layer of organization in the brain, were published in Nature, ScienceDaily reported.
Lipids — the fatty molecules that make up the membranes surrounding neurons, contribute to the myelin insulation that protects nerve fibers, and play important roles in communication between brain cells — have received far less attention than the brain’s cells, connections, genes and proteins, ScienceDaily said. Conventional imaging techniques cannot easily distinguish individual lipid molecules, leaving a major gap in understanding of the brain’s chemical organization.
“So scientists have had only a blurry picture of how lipids differ from one part of the brain to another,” Giovanni D’Angelo, professor at The Kristian Gerhard Jebsen Foundation Chair in Nutrition and Metabolism at EPFL, told ScienceDaily. “That gap matters, because changes in brain lipids are increasingly linked to conditions from depression to Alzheimer’s disease.”
A team led by D’Angelo, Luca Fusar Bassini and Gioele La Manno built the atlas using mass spectrometry imaging, a technique in which a laser scans thin sections of brain tissue one location at a time, producing detailed information about which lipids are present and where they are found, ScienceDaily reported. The researchers examined 172 different lipids in 109 brain slices collected from 11 mice, generating approximately 7 million measurements that were combined into a comprehensive 3D reconstruction using machine-learning tools developed specifically for the project, according to ScienceDaily.
The resulting atlas revealed 539 territories, each with a characteristic combination of lipids that creates a recognizable chemical signature, ScienceDaily reported. Many correspond to established brain structures and cell types, while others expose chemical boundaries that previous approaches had overlooked, including unexpected relationships between groups of nerve cell bodies and distant regions connected by their fibers — connections that have often been difficult to detect using maps based on gene activity. The patterns are so distinctive that researchers could identify where a brain tissue sample originated simply by examining its lipid composition, ScienceDaily said. “In effect, lipids work like postal codes, giving distant but related parts of the brain the same chemical address,” D’Angelo said.
The atlas also uncovered surprising differences within parts of the brain previously considered relatively uniform. White matter, the tissue containing the nerve fibers that connect brain regions, contains numerous distinct lipid zones rather than a largely consistent chemical composition. “This shows that the cells which make myelin are far more varied in their chemistry than their genes alone would suggest,” Fusar Bassini said, according to ScienceDaily. The team also detected previously unrecognized chemical boundaries in the choroid plexus, the structure that produces cerebrospinal fluid, and in the tissues lining the brain’s internal cavities.
Beyond the brain’s structure, the atlas offered insight into how that structure changes during pregnancy. When the researchers examined pregnant mice, they found substantial shifts in lipid composition across numerous brain regions — changes more pronounced than the typical lipid differences between male and female mice, ScienceDaily reported. The cortex, the brain’s outer layer, showed particularly extensive changes, and levels of galactosyl ceramide, an important component of myelin, increased sharply through much of the brain’s white matter. “Together, these shifts suggest the brain retunes its own wiring to meet the demands of pregnancy,” La Manno said, according to ScienceDaily.
The Lipid Brain Atlas is freely available online and establishes a detailed reference for healthy mouse brain tissue, allowing scientists to investigate how disruptions in lipid distribution might contribute to brain development, aging and disorders such as Alzheimer’s disease and depression, ScienceDaily said. The specific mouse brain map cannot be applied directly to humans, but the approach used to create it could help researchers uncover comparable patterns in the human brain, ScienceDaily added.