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Primary culture of oligodendrocyte-progenitor cells from rat brain:
electrophysiological properties and effect of ischemic factors.
By Roeland Buckinx
Recent research has
shown that there can be a hypoxic (shortage of oxygen) and/or an
ischemic (too low blood flow) component in Multiple Sclerosis
[1,2]. The cell that is primarily affected in MS is the oligodendrocyte,
which is very important for a proper conduction of signals in the
central nervous system. Since this cell type plays such a big
role, its functional recovery is important in recovery during MS.
The cells that develop into mature oligodendrocytes are called
progenitor cells, and the presence and health of these cells may be
crucial for recovery of the oligodendrocyte population when affected by
MS. Unfortunately, these progenitor cells are also very sensitive to
ischemia. [3-5] Given this background information, we want to look at the influences of ischemic factors on
the progenitor cells of oligodendrocytes. A couple of these ischemic
factors are a rise in calcium-concentration in the cell, a drop in the
amount of intracellular ATP (a crucial molecule in
the bioenergetics of cells), a
local acidification and a local shortage of oxygen. We especially focus
on the electrofysiological changes in these cells. We examine the ion
currents through the membrane of these cells. The ion currents that pass
through a cell membrane are very important for the ion homeostasis of
the cellular cytosol.
We can measure these current with the help of the “whole cell” patch
clamp technique, for which the basic technique was developed by Erwin
Neher and Bert Sakmann. For this achievement they were awarded the Nobel
Price in Medicine in 1991 (http://www.nobel.se/medicine/laureates/1991/).
When using the “whole cell” variant of this technique we place a
very small glass pipette on the cell membrane, and cause a small
negative pressure in the pipette, which eventually breaks the membrane locally
(fig. 1). This procedure allows to get access to the inside of the cell
and to dialyse its interior. The patch clamp technique allows the researcher to
clamp the membrane voltage to a certain value, using an appropriate
electrical circuit. In this way, we can measure and study the ion
currents that cross the membrane in function of the applied membrane
potential. We intend to study how the above mentioned ischemic factors
might affect the different ion currents.
Research
funded by a Ph.D. grant of the Institute for the Promotion of Innovation
through Science and Technology in Flanders (IWT Vlaanderen).
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Lucchinetti,
C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M., and Lassmann,
H. Heterogeneity of multiple sclerosis lesions: implications for the
pathogenesis of demyelination. Ann Neurol 47: 707-17, 2000.
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Lassmann,
H. Hypoxia-like tissue injury as a component of multiple sclerosis
lesions. J Neurol Sci 206: 187-91, 2003.
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Blakemore,
W. F. and Keirstead, H. S. The origin of remyelinating cells in the
central nervous system. J Neuroimmunol 98: 69-76, 1999.
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Levine,
J. M. , Reynolds, R., and Fawcett, J. W. The oligodendrocyte precursor
cell in health and disease. Trends Neurosci 24: 39-47, 2001.
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Paz
Soldan, M. M. and Rodriguez, M. Heterogeneity of pathogenesis in
multiple sclerosis: implications for promotion of remyelination. J
Infect Dis 186 Suppl 2: S248-53, 2002.
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