A 3D Neurosterol Atlas of Mouse Brain

Award Number
BB/T018518/1
Status / Stage
Active
Dates
1 November 2020 -
29 February 2024
Duration (calculated)
03 years 03 months
Funder(s)
BBSRC (UKRI)
Funding Amount
£248,091.00
Funder/Grant study page
BBSRC UKRI
Contracted Centre
University of Edinburgh
Principal Investigator
Professor Ruth Andrew
PI Contact
Ruth.Andrew@ed.ac.uk
PI ORCID
0000-0002-6916-2994
WHO Catergories
Understanding Underlying Disease
Disease Type
Dementia (Unspecified)

CPEC Review Info
Reference ID724
ResearcherReside Team
Published07/07/2023

Data

Award NumberBB/T018518/1
Status / StageActive
Start Date20201101
End Date20240229
Duration (calculated) 03 years 03 months
Funder/Grant study pageBBSRC UKRI
Contracted CentreUniversity of Edinburgh
Funding Amount£248,091.00

Abstract

The brain is a remarkably complex organ. To understand brain function, it requires multidisciplinary technologies and multiple levels of data. There are a number of big initiatives worldwide to map the brain. Current activities are focused on mapping gene expression, cell type and connectivity across the entire brain. Despite these efforts, little is known about the landscape of the metabolome or lipidome across the brain. The sterol category of lipids, including cholesterol, its precursors, and oxysterols and steroids, represent one of the dominating lipid classes in brain and sterol homeostasis plays a critical role in neurophysiology. It is recognised that a lack of quantitative spatial information on steroids and sterols/oxysterols in brain subregions is a key gap in our understanding of the mechanisms underlying health and healthy aging. The aim of this proposal is to create a web-based 3D Neurosterol Atlas of Mouse Brains utilising our recently-developed on tissue derivatisation and mass spectrometry imaging (MSI) technology. On-tissue derivatisation overcomes the limitations of previous MSI techniques for analysis of low abundance and difficult to ionise sterol molecules. We have successfully combined on-tissue derivatisation with MALDI-MSI to image neurosteroids and cholesterol, and combined it with liquid-extraction for surface analysis (LESA) and liquid chromatography – mass spectrometry (LC-MS), i.e. LESA-LC-MS, to image cholesterol precursors and oxysterols, allowing isomer differentiation and structure identification. Here we will scale up our effort and use the Allen Mouse Brain Atlas as a template to create a web-based interactive 3D Neurosterol Atlas of Mouse Brain including developmental, young adult and aged mice of both sexes. The resource will support neuroscience research in many areas, including myelination and repair, neurotransmitter receptors, stress response and neuroprotection and regeneration.

Aims

The aim of this proposal is to create a web-based 3D Neurosterol Atlas of Mouse Brains utilising our recently-developed on tissue derivatisation and mass spectrometry imaging (MSI) technology.