Wednesday, 15 April 2015

Neurofilaments may start repair in myelin forming cells

Fressinaud C, Eyer J. Neurofilaments and nfl-tbs.40-63 peptide penetrate oligodendrocytes through clathrin-dependent endocytosis to promote their growth and survival in vitro. Neuroscience. 2015 A. pii: S0306-4522(15)00328-0. doi: 10.1016/j.neuroscience.2015.04.003. [Epub ahead of print]


Neurofilaments (NF) are released into the cerebrospinal fluid (CSF) during multiple scerosis (MS), but their role outside the axon is still unknown. In vitro NF fractions, as well as tubulin (TUB), increase oligodendrocyte (OL) progenitor proliferation and/or their differentiation depending on the stage of their purification. However the mechanism by which NF enter these cells, as well as that of synthetic peptides displaying NFL-tubulin binding site (NFL-TBS. 40-63), remains elusive. Using rat OL secondary cultures we localized NF, TUB, and NFL-TBS.40-63 by double immunocytochemistry and confocal microscopy. These proteins were localized in the cytoplasmic processes of myelin basic protein (MBP+) expressing OL. Similarly biotinylated NFL-TBS.40-63 synthetic peptides and KER-TBS.1-24 were detected in OL progenitors, differentiated (CNP+) and MBP+ OL. In addition, NFL-TBS.40-63 colocalized with cholera toxin, a known marker of endocytosis, within the cells. Pretreatment of OL by methyl β cyclodextrin abolishes both cholera toxin and NFL-TBS.40-63 uptake, indicating endocytosis. Clathrin-dependent endocytosis was further confirmed by treatment with dynasore, a dynamin inhibitor, which inhibited the uptake of peptides, as well as NFP2 fractions, by 50%. This study demonstrates that axon cytoskeletal proteins and peptides can be internalized by OL through endocytosis. This process could be involved during demyelination, and the release of axon proteins might promote remyelination.
We are looking for neurofilaments in the blood or spinal fluid as markers of nerve damage, but this study suggests that they may so useful function and may act as a trigger to oligodendrocytes to say "start repair"

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