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 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

A simple method to determine phase preference of proteins on live cell membranes
Journal News

A simple method to determine phase preference of proteins on live cell membranes

May 22, 2022

“The phase preference of molecules used to be difficult and time-consuming to establish. This new method, detected by chance, provides results in at most 15 minutes on live cells,” Thorsten Wohland said.

Study of Alzheimer’s marker prompts warning about serine supplements
News

Study of Alzheimer’s marker prompts warning about serine supplements

May 20, 2022

They have been advertised to improve memory and cognitive function.

Why is the 100-year-old BCG vaccine so broadly protective in newborns?
News

Why is the 100-year-old BCG vaccine so broadly protective in newborns?

May 19, 2022

Study finds changes in metabolite and lipid profiles, providing clues for designing future vaccines for newborns.

How genome organization influences cell fate
News

How genome organization influences cell fate

May 17, 2022

UC Riverside-led study identifies how blood stem cells maintain their fate.

Corals and sea anemones turn sunscreen into toxins
News

Corals and sea anemones turn sunscreen into toxins

May 14, 2022

Understanding how could help save coral reefs.

The body’s response to allergic asthma also helps protect against COVID-19
News

The body’s response to allergic asthma also helps protect against COVID-19

May 14, 2022

It all comes down to an immune system protein known as interleukin-13