Journal News

JLR: A close-up of the lipids in Niemann–Pick disease

Laurel Oldach
Dec. 1, 2018

Researchers at the University of Illinois at Chicago have used mass spectrometry imaging to map lipid accumulation in Niemann–Pick disease with unprecedented detail. Their results were published in a recent issue of the Journal of Lipid Research.

There are three major forms of Niemann–Pick disease. All are genetic and rare. Type C, or NPC, results in accumulation of cholesterol and complex lipids known as gangliosides in the endosomes and lysosomes of cells. This accumulation leads to neurodegeneration, killing patients when they are young. Many die before they’re 10. It’s rare for one to live to 40.

Cerebellum imageThis image of a cerebellum from a mouse with Niemann–Pick C was generated using fluorescence immunolabeling, which is an effective technique for determining protein distribution but cannot capture the location of gangliosides and other lipids that accumulate and cause the disease.Williams/NICHD
Based on the way movement and cognition problems emerge in NPC, it seems that different brain regions degenerate at varying stages of the disease. To understand this staging better, it would be useful to visualize lipid accumulation in specific brain regions. This isn’t easy to do with traditional methods, because antibodies against gangliosides are not very specific, so most studies of lipid accumulation in Niemann–Pick disease use homogenized tissue samples from mice with the disease and measure bulk lipids by mass spectrometry.

To achieve greater spatial accuracy, researchers in Stephanie Cologna’s lab used mass spectrometry imaging to look closely at lipids in specific regions of the cerebellum in mice with early-stage NPC. Mass spectrometry imaging, which does not require antibodies or chemical labeling, works by representing small areas of a tissue sample as pixels. The researcher coats a tissue sample in a matrix that helps it to ionize and then collects mass spectra from many tiny areas within that sample.

Each spectrum from one pixel includes information about the abundance of many lipid species. The team used the information about different molecules to make images representing the distribution of lipids across the cerebellum.

Mindful of variations in the intensity of matrix-assisted laser desorption/ionization spectra that can arise from uneven application of the matrix or variability among samples, the team, led by graduate student Fernando Tobias, also devised an algorithm to evaluate the most abundant signals. The algorithm let them filter out noise and compare measurements of wild-type and NPC brain samples more reliably with many replicates.

Once they compared lipid distributions across the cerebellum, the team made the interesting observation that, while two types of ganglioside (GM2 and GM3) are drastically higher in the NPC mouse’s cerebellum, GM1 seems to go up throughout the brain. Also, GM2 elevation is very tightly localized in a part of the cerebellum called lobule X, but it’s not yet clear what that might mean.

The researchers intend to continue using mass spectrometry imaging to get a more granular picture of the disease course.

 

Laurel Oldach

Laurel Oldach is a science writer for the ASBMB.

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

A balancing game with implications for neurodegenerative disease
Journal News

A balancing game with implications for neurodegenerative disease

June 8, 2021

The relationship between two proteins, one essential to mitochondrial fission and the other found in Alzheimer’s tissue, might hold the key to how disease alters the fission–fusion balance.

Can people vaccinated against COVID-19 still spread the coronavirus?
News

Can people vaccinated against COVID-19 still spread the coronavirus?

June 6, 2021

Preliminary evidence seems to suggest that someone who’s vaccinated is less likely transmit the virus, but the proof is not yet ironclad.

Addgene expands its collection into antibodies
News

Addgene expands its collection into antibodies

June 4, 2021

The reagent repository Addgene, known for distribution and quality control of plasmids for open science, is expanding into recombinant antibodies and nanobodies in partnership with NeuroMab.

Study reveals experimental targets for lymphoma research
Journal News

Study reveals experimental targets for lymphoma research

June 3, 2021

An enzyme previously linked to lymphoma development may have more functions than previously thought.

Exploring underappreciated molecules and new cities
Interview

Exploring underappreciated molecules and new cities

June 2, 2021

Neurochemist Xianlin Han has been an associate editor for the Journal of Lipid Research since 2019.

Researchers target cell membrane for cancer research
Journal News

Researchers target cell membrane for cancer research

June 1, 2021

“The central idea is that if you alter the composition of the cell membrane, you can potentially alter the functionality of the proteins within the membrane and thus the disease overall.”