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Welcome
Introduction
How
to register as a tissue donor
Raising awareness of all those affected by MS
Donation
of Tissue
Requesting
tissue for research on multiple sclerosis
Promoting the Tissue Bank in the research community
The Bank
Statement
Articles
Links:
Department
of Cellular and Molecular Neuroscience
Department
of Neuropathology
Multiple Sclerosis Society of Great
Britain and Northern Ireland
International Federation of Multiple Sclerosis
Societies
E-mail: ukmstissuebank@imperial.ac.uk
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the Bank Statement
News from
The UK Multiple
Sclerosis Tissue Bank
.
(The Bank Statement is also available as a PDF document.)
The 6 projects
described below were made possible only by the generosity and forethought of
the people who have donated their tissues to research on MS.
Is working
harder bad for the axon?
Dr Philip Nichols
MS Research Group, University of Newcastle
upon Tyne
An examination of MS lesions reveals two casualties myelin and axons. What is
less clear is how these injuries occur. Over the last two years, Dr Nichols
group has been trying to find out how axons are damaged in MS lesions; and
what role special structures within the nerve cell - the mitochondria play in
this damage.
The mitochondria, one shown
here in a cartoon, provide energy to the cell and so are referred to as the
cell's batteries In nerve cells, mitochondria provide the energy that is
needed to drive nerve impulses along the axon. The group asked do the
batteries in axons within lesions have to work harder? In order to answer
this they examined brain tissue from MS donors that contained a lesion and an
adjacent sample that appeared normal They first confirmed the presence of a
lesion by treating a very thin slice of the tissue with a dye that stains
myelin blue. They then cut another slice and used a special dye with which
they could see how hard the mitochondria were working.
The picture in the top left panel (below) shows normal tissue with normal
amounts of myelin (dark blue); a lesion in which the myelin has been
destroyed is shown top right (lack of blue). The brown stain in the bottom
panels shows the activity of mitochondria the darker staining of the tissue
containing the lesion (bottom right) demonstrates that the mitochondria were
more active in the lesion.
This is perfectly
understandable, as an axon devoid of the insulating layer of myelin will need
more energy to conduct nerve impulses than a fully insulated, myelinated
axon. But, is it possible that the very system by which the axon is trying to
cope with the lack of myelin is actually making it more vulnerable to damage
and eventual death? In order to answer this, Dr Nichols group is now trying
to find out whether an unfortunate side effect of the increased activity of
the mitochondria could contribute to axons being damaged within lesions.
Understanding the exact mechanism of this could provide a target for
treatments aimed at stopping damage to axons and this would in turn bring us
one step closer to limiting or even preventing the disability caused by MS.
Chemicals
that draw big eaters to a site of injury
Professor Yoh Matsumoto
Tokyo Metropolitan Institute for
Neuroscience, Tokyo, Japan
Professor Matsumoto's group is following another lead to explain the injury
to axons. The amount of axonal damage within a lesion has been linked to the
number of a particular type of cell called a macrophage present at the crime
scene Macrophages release toxic chemicals that kill bacteria and tumour
cells, and they then engulf and digest the resulting debris. Since these
activities could be directed to injuring axons, it is vital to control this
powerful cell within the brain. Professor Matsumoto has gone to the very
beginning of the chain of events and asked: What initially draws macrophages
to a site where axons are or about to be injured?
Chemicals that cause cells to move towards the site of release are called
chemokines, and the group found two types in MS lesions: monocyte chemoattractant-1
(MCP-1) and interferon-gamma inducible protein-10 (IP-10). It is known that
MS lesions grow by expanding outward from a central starting point. This
means that in a large active lesion, the ongoing destruction will be
occurring on the lesion edge. High concentrations of MCP-1 and IP-10 were
found on the rim of the lesions, and low levels in the inactive, lesion
centre and in the surrounding normal tissue.
These pictures from Professor Matsumoto's research show on the left a thin
slice of tissue treated with the blue myelin dye demonstrating the presence
of a large lesion. The next slice was treated with a stain that picks up the
chemokine MCP-1. The three high power views on the right, show low amounts of
MCP-10 at the centre and outside the lesion and large amounts on the lesion
rim (small brown dots). Similar pictures were seen when slices were stained
for IP-10.
Large numbers of macrophages
were also found in the rim, and these had on their surface receptors that
would capture MCP-10 and IP-10. Importantly these macrophages had
produced a toxic enzyme (matrix metalloproteinase) that is capable of
damaging axons.
So it seems that as lesions expand, more and more macrophages are drawn to
the active edge by MCP-1 and IP-10; once there, the cells attack the axon,
and perhaps the myelin and then engulf and digest fragments of the resulting
debris. The important role played by chemokines in guiding macrophages
to the edge of a lesion, provides a target for therapies, since stopping the
action of chemokines would stop macrophages from reaching the crime scene and
injuring
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