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.

 

Enjoy reading ASBMB Today?

Become a member to receive the print edition monthly and the digital edition weekly.

Learn more
Laurel Oldach

Laurel Oldach is a former science writer for the ASBMB.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Evolutionary constraints on disordered proteins
Feature

Evolutionary constraints on disordered proteins

Dec. 5, 2022

Best of BMB 2022: “There’s evidence that there must be conservation of function — so how does this happen, if the sequence changes so much?”

COVID-19, preprints and journalists
Science Communication

COVID-19, preprints and journalists

Dec. 3, 2022

Researchers find that news stories often fail to mention when studies haven’t been peer reviewed.

From the journals: MCP
Journal News

From the journals: MCP

Dec. 2, 2022

Muscling in on a signaling pathway. Probing weaknesses in the T cell surface. Improving single-cell proteomics two ways. Read about papers on these topics recently published in the journal Molecular & Cellular Proteomics.

Unconventional phosphoinositide synthesis
Lipid News

Unconventional phosphoinositide synthesis

Nov. 29, 2022

Researchers uncover a clue to how disease-causing bacteria synthesize the tiny lipids known as 3-phosphoinositides to hijack host cells.

From the journals: JLR
Journal News

From the journals: JLR

Nov. 25, 2022

A new way to measure lipoprotein(a). A new source of metabolized cholesterol. A new way to count ceramides. Read about articles on these topics recently published in the Journal of Lipid Research.

How proteolysis controls the Legionnaires’ pathogen
Journal News

How proteolysis controls the Legionnaires’ pathogen

Nov. 24, 2022

The bacterium that causes this severe pneumonia has a biphasic life cycle that depends on regulation of protein homeostasis.