Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism

Proceedings of the National Academy of Sciences of the United States of America
Eylan YutucWilliam J Griffiths

Abstract

Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatization in combination with microliquid extraction for surface analysis and liquid chromatography-mass spectrometry to locate sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400-µm spot diameter with a limit of quantification of 0.01 ng/mm2 It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low-abundance and difficult-to-ionize sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild-type and cholesterol 24S-hydroxylase knockout mouse brain. The technology described provides a powerful tool for future studies of ...Continue Reading

References

Feb 7, 1997·The Journal of Biological Chemistry·J M LehmannT M Willson
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·E G LundD W Russell
Jan 5, 2000·Physiological Reviews·G J Schroepfer
Oct 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ling WangJan-Ake Gustafsson
Apr 11, 2003·The Journal of Biological Chemistry·Erik G LundDavid W Russell
Jun 12, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Ying Yong LinSeymour Lieberman
Mar 3, 2005·Journal of Lipid Research·Maura HeverinIngemar Björkhem
Aug 30, 2005·The Journal of Clinical Investigation·Luigi PuglielliAshley I Bush
Mar 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Tiina J KottiDavid W Russell
Dec 8, 2006·Nature·Ed S LeinAllan R Jones
Jan 4, 2007·The Journal of Biological Chemistry·Jennifer R DwyerFarhad Parhami
Apr 13, 2007·Proceedings of the National Academy of Sciences of the United States of America·Arun RadhakrishnanJoseph L Goldstein
Feb 21, 2008·The Journal of Biological Chemistry·Robert C Murphy, Kyle M Johnson
Jun 6, 2009·Annual Review of Biochemistry·David W RussellTiina Kotti
Dec 10, 2009·The Journal of Biological Chemistry·Michael OgundareWilliam J Griffiths
Apr 27, 2011·Journal of Cellular Physiology·Yen-Feng ChiangMeng-Chun Hu
Sep 29, 2011·Chemical Reviews·Karin A Zemski BerryRobert C Murphy
Sep 29, 2011·Journal of the American Society for Mass Spectrometry·Joseph A HankinRobert C Murphy
Jan 11, 2012·Nature Chemical Biology·Sigrid NachtergaeleRajat Rohatgi
Mar 20, 2012·Journal of the American Society for Mass Spectrometry·Abraham K Badu-TawiahR Graham Cooks
Nov 1, 2012·Biochimie·Ingemar Björkhem
Jan 8, 2013·Nature Chemical Biology·Spyridon TheofilopoulosErnest Arenas
Apr 24, 2013·The Journal of Biological Chemistry·Jessica F FriszMary L Kraft
Jun 26, 2013·Developmental Disabilities Research Reviews·Shibani KanungoRobert D Steiner
Jul 9, 2013·Nature Chemical Biology·Daniel NedelcuAdrian Salic
Oct 19, 2013·Analytical Chemistry·Diego F CobiceRuth Andrew
Nov 1, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Steven M PaulCharles F Zorumski
Dec 25, 2013·Journal of Lipid Research·Karin A Zemski BerryNicolas G Bazan
Feb 4, 2014·Biochemical and Biophysical Research Communications·Hanne Roberg-LarsenSteven Ray Wilson
Feb 5, 2014·Biochemical and Biophysical Research Communications·Anna MeljonWilliam J Griffiths
Apr 2, 2014·Journal of Proteomics·Megan M GesselRichard M Caprioli
May 17, 2014·Biochemical and Biophysical Research Communications·Yuchen WangWilliam J Griffiths
Jul 16, 2014·Journal of Lipid Research·Sandeep GoyalF Peter Guengerich
Oct 2, 2014·The Journal of Clinical Investigation·Spyridon TheofilopoulosYuqin Wang
Nov 14, 2014·Journal of the American Society for Mass Spectrometry·Reinaldo AlmeidaChrister S Ejsing

❮ Previous
Next ❯

Citations

Nov 10, 2020·Mass Spectrometry Reviews·Kellen DeLaneyLingjun Li
Nov 17, 2020·Expert Review of Proteomics·Yuqin WangWilliam J Griffiths
Nov 28, 2020·The Journal of Steroid Biochemistry and Molecular Biology·Jonas Abdel-KhalikYuqin Wang
Jan 13, 2021·Mass Spectrometry Reviews·Carla HarkinDiego F Cobice
Jan 27, 2021·Free Radical Research·Sayuri MiyamotoLucas G Viviani
Jan 29, 2021·The FEBS Journal·Yuqin WangWilliam J Griffiths
Apr 3, 2021·Acta Neuropathologica Communications·Tahir AliSabine Gilch
Apr 7, 2021·Molecular Psychiatry·Zeljka KoradeKároly Mirnics
Jun 3, 2021·Antioxidants·Paola GambaGabriella Leonarduzzi
Jul 27, 2021·Frontiers in Aging Neuroscience·Irina A Pikuleva, Nathalie Cartier

❮ Previous
Next ❯

Methods Mentioned

BETA
laser capture microdissection

Software Mentioned

GraphPad Prism
NanoSIMS
SPSS Statistics
Advion ChipsoftX
GraphPad

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.