A 3D Neurosterol Atlas of Mouse Brain
Award Number
BB/T018518/1Programme
Research GrantStatus / Stage
ActiveDates
1 November 2021 -29 February 2024
Duration (calculated)
02 years 03 monthsFunder(s)
BBSRC (UKRI)Funding Amount
£248,091.00Funder/Grant study page
BBSRC UKRIContracted Centre
University of EdinburghPrincipal Investigator
Professor Ruth AndrewPI Contact
Ruth.Andrew@ed.ac.ukPI ORCID
0000-0002-6916-2994WHO Catergories
Understanding Underlying DiseaseDisease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 684 |
|---|---|
| Researcher | Reside Team |
| Published | 07/07/2023 |
Data
| Award Number | BB/T018518/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20211101 |
| End Date | 20240229 |
| Duration (calculated) | 02 years 03 months |
| Funder/Grant study page | BBSRC UKRI |
| Contracted Centre | University 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.
Plain English Summary
The sterol category of lipids, including cholesterol, its precursors and metabolites (oxysterols and steroids), are important biomolecules in the brain. Cholesterol is the major component of the myelin sheaths which surround neurons. Many sterols are biologically active molecules regulating many brain functions and behaviours, such as memory, cognition, stress and mood. These molecules are localized and enriched in different brain regions according to the biological roles they play. However, sterol distributions in brain are poorly defined due to lack of technology which has hampered our understanding about how the brain functions and loses function with ageing. Bioimaging provides an image of biomolecular abundance, molecule by molecule, in a tissue, allowing visualization of the quantitative and spatial distribution of different molecules within a tissue. Mass spectrometry imaging is an emerging powerful tool for bioimaging. We will use this technology to construct a 3D map or atlas of sterol molecules in the brains of mice from developmental stage to young adult to aged mice. Scientists will use our Atlas to find out where different sterol molecules are located in the brain and how their abundance correlates with brain functional region. The resource will support many aspects of neuroscience research which address healthy aging.
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.