Brain atlas reveals 539 chemical regions mapped by fats

Scientists have produced the most detailed map yet of how fats are arranged in the brain, revealing 539 chemically distinct regions, some of which had never been seen before.

Lipids, the fatty molecules that make up cell membranes and the insulating myelin around nerve fibres, are fundamental to how the brain works. But they have been hard to map, because conventional imaging struggles to tell individual lipid molecules apart.

How the map was made

A team at EPFL, the Swiss Federal Institute of Technology in Lausanne, led by Giovanni D'Angelo, Luca Fusar Bassini and Gioele La Manno, used mass spectrometry imaging, in which a laser scans thin slices of brain tissue point by point to identify the molecules present.

They studied 172 different lipids in 109 brain slices from 11 mice, generating about seven million measurements, and used machine learning tools developed for the project to build a three-dimensional reconstruction. The work is published in Nature.

"Lipids work like postal codes"

The resulting Lipid Brain Atlas revealed 539 territories, which the team called "lipizones", each with its own chemical signature. The patterns are so distinctive that the researchers could tell where a sample came from just by looking at its lipids.

Many lipizones matched known brain structures. Others revealed links between groups of nerve cells and the distant regions connected to them by their fibres, links that maps based on gene activity often miss. "In effect, lipids work like postal codes, giving distant but related parts of the brain the same chemical address," Professor D'Angelo said.

The atlas also found surprising variety in white matter, the tissue made of nerve fibres, which had been thought to be chemically uniform. "This shows that the cells which make myelin are far more varied in their chemistry than their genes alone would suggest," said Dr Fusar Bassini.

Changes in pregnancy

In pregnant mice, the researchers found big shifts in lipid make-up across many brain regions, larger than the usual differences between males and females. Levels of a key myelin component rose sharply in white matter. "These shifts suggest the brain retunes its own wiring to meet the demands of pregnancy," said Dr La Manno.

Why it matters

Changes in brain lipids have been increasingly linked to conditions including depression and Alzheimer's disease. The atlas, which is freely available online, gives scientists a reference for a healthy brain against which to compare disease.

The mouse map cannot be applied directly to people, but the researchers say the method could reveal similar patterns in the human brain. "What transfers to humans isn't the map, it's the method, and the fact that we now know that a healthy brain has a very organised lipid map at all," Dr Fusar Bassini said.

The brain is nearly 60% fat by dry weight, more than any other organ, which is one reason scientists have long suspected lipids play a much bigger role in brain health than they have been able to measure.