A team of researchers led by Swansea University have developed new
technology to monitor cholesterol in brain tissue which could uncover
its relation to neurodegenerative disease and pave the way for the
development of new treatments.
The research, published in the Proceedings of the National Academy of Sciences of the USA, shows the major locations of cholesterol in the brain and what molecules it can be converted to.
The brain is a remarkably complex organ, with cholesterol and its
metabolites underpinning the brain’s function. Dysregulated cholesterol
metabolism is linked to a number of neurodegenerative disorders
including Alzheimer’s, Parkinson’s, Huntington’s disease, multiple
sclerosis and motor neurone disease.
It is known that cholesterol is not evenly distributed across
different brain regions; however, up until now there has been no
technology available to map cholesterol metabolism in defined locations
of the brain at microscopic levels, and to visualise how it changes in
pathological niches in the brain.
Here, researchers describe an advanced mass spectrometry imaging
platform to reveal spatial cholesterol metabolism in mouse brain at
micrometre resolution from tissue slices. The researchers mapped not
only cholesterol, but also biologically active metabolites arising from
cholesterol turnover. For example, they found that
24S-hydroxycholesterol, the major cholesterol metabolite in the brain,
is about ten times more abundant in striatum than in the cerebellum, two
regions involved in different ways in voluntary movement and cognition.
The new technology comes from a decade of research at Swansea
University where the team have worked out methods to reveal the
different metabolites of cholesterol in very small quantities of the
brain, as small as the tip of a ballpoint pen.
Professor William Griffiths, who co-led the study from Swansea
University added: “Although our work was with a mouse, the technology
can similarly be used in humans in a research lab or a clinical setting,
and could have revolutionary value when linked to neurosurgery.
“Tissue excised during surgery could rapidly be profiled by our
method in-clinic and used to distinguish healthy from diseased tissue,
informing the surgeon on the next step of the operation.”
Professor Yuqin Wang added: “This technology which precisely locates
molecules in the brain will further our understanding of the complexity
of brain function and how it changes in neurodegenerative disorders.
“Our results show that cholesterol turnover is particularly high in
striatum, the area most affected in Huntington’s disease. We will apply
this method to find out how cholesterol metabolism is associated with
this disease. This may lead to the development of new therapies to a
disease which currently has no cure.”
https://www.eurekalert.org/pub_releases/2020-05/su-rdn052920.php
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